1989 — 1990 |
Lerman, Caryn |
R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Improving Adherence in Women With Abnormal Mammograms @ Fox Chase Cancer Center
As a consequence of more widespread use of mammography, there is a growing number of American women who have received an abnormal result on a screening mammogram. Our preliminary research suggests that there are significant psychological costs associated with this experience. Moreover, these psychological consequences of having an abnormal mammogram may interfere with adherence to future breast screening and follow-up. To date, however, there have been no studies conducted to understand this phenomenon and no interventions designed to meet the needs of women with abnormal mammograms. In the proposed study, we will develop and test a psychoeducational intervention to promote adherence to annual mammography and follow-up in women who have had abnormal mammograms. We also will evaluate the relative impact on adherence of two different styles of presenting educational information. The study population will be 600 women aged 50 and older who are participants of US HEALTHCHECK, a breast screening program for members of HMO PA/NJ. They will be women who have had a recent abnormal mammogram and who are eligible to receive their annual screening mammogram. Subjects will be randomly assigned either to receive the standard US HEALTHCHECK annual breast screening packet/referral (control) or the standard packet/referral plus a psychoeducational manual which is tailored to the needs of women with abnormal mammograms (experimental). Pre-intervention telephone surveys will be used to evaluate the independent effects of sociodemographic characteristics and baseline levels of knowledge, health beliefs, coping, and physician-patient communication on women's subsequent adherence to screening mammography and follow-up. Post intervention surveys will be used to determine the impact of the interventions on adherence, as well as on knowledge, health beliefs and coping variables. Medical and radiology records will be utilized to verify self-report data on mammography adherence and follow-up. The proposed intervention was chosen for its potential efficacy and ease of replication. If effective, it can be applied to diverse problems of cancer control, such as promoting continued adherence and follow-up among persons with positive stool blood tests or Pap smears.
|
0.894 |
1991 — 1993 |
Lerman, Caryn |
K07Activity Code Description: To create and encourage a stimulating approach to disease curricula that will attract high quality students, foster academic career development of promising young teacher-investigators, develop and implement excellent multidisciplinary curricula through interchange of ideas and enable the grantee institution to strengthen its existing teaching program. |
Impact of Genetic Counseling For Breast Cancer @ Fox Chase Cancer Center
Basic science investigations have identified an increasingly large number of genetic factors important in cancer. By communicating this genetic information to high risk individuals, we can facilitate informed decision- making about participation in cancer prevention and early detection programs. The purpose of the proposed program is to improve adherence to cancer control regimens among persons with a genetic susceptibility to develop cancer. Subjects for the primary project will be 750 women aged 40-65 who have a positive family history of breast cancer in at least one first-degree relative. A randomized factorial design will be used to evaluate the impact of Breast Cancer Risk Counseling (BCRC), a form of genetic counseling for women at high risk for breast cancer. In addition, two different styles of presenting cancer control recommendations in BCRC will be tested. The BCRC intervention will be based on the traditional medical genetics counseling model, but will concentrate on breast cancer surveillance, rather than on reproductive decisions. Telephone interviews will be conducted prior to the interventions to collect familial and medical data to calculate individualized breast cancer risks and to assess baseline risk perceptions, psychosocial functioning, and breast screening patterns. Post-intervention and follow-up surveys will be used to assess the short- and long-term impact of the interventions on these outcomes. Also, subgroups of women who are most and least likely to benefit from the different BCRC interventions will be identified, based on their precounseling psychosocial characteristics and demographic backgrounds. The information obtained from this primary project will lay the foundation for other studies to improve adherence to cancer control practices in diverse high-risk populations. The interventions proposed for these studies are replicable, and, if effective, can be administered by nurses and physicians in medical practice.
|
0.894 |
1992 — 1996 |
Lerman, Caryn |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Improving Adherence in Women At Risk For Breast Cancer |
0.948 |
1993 — 1996 |
Lerman, Caryn |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Counseling Women At Risk For Breast Cancer
We propose to conduct a multisite evaluation of a brief cognitive- behavioral intervention to promote quality of life and increase adherence to early detection regimens among first-degree relatives (FDRs) of newly- diagnosed breast cancer patients. A randomized trial and a diffusion component will be conducted. The specific aims of the randomized trial are to: (1) evaluate the impact of Problem-Solving Training (PST) on adjustment and adherence in this population, and (2) identify subgroups of women who are most likely to benefit from PST (i.e., based on their baseline sociodemographic characteristics and coping styles). Subjects will be 16OO women ages 35 and older. They will identified through index breast cancer patients at six Comprehensive Cancer Centers which comprise the High Risk Breast Cancer Consortium. Subjects will be randomized to one of two study conditions: (1) General Health Counseling (control) and (2) Problem-Solving Training. The PST intervention is based on Lazarus's Transactional Model of Stress and Coping and on extensive research on cognitive-behavioral interventions. This nurse-delivered intervention is designed to promote adaptive problem appraisal and provide skills to identify and implement effective coping responses. Telephone interviews and mailed questionnaires will be completed 1-month pre-intervention to collect data on sociodemographics and coping styles (i.e., information- seeking vs. information-avoidance), and to establish baseline levels of mediating process variables (i.e., primary and secondary appraisals, coping efforts, problem-solving skill), quality of life outcomes (i.e., breast cancer worries, stress impact, mood functional health status) and adherence outcomes (i.e., mammography, clinical breast examination, breast self-examination). Follow-up interviews and mailed questionnaires will be administered at 3- and 12-months post-intervention to assess the short and long-term impact of the interventions. Regressive models will be used to identify key variables and causal processes associated with positive changes in outcomes. In addition, as part of a diffusion component, we will determine the feasibility, potential efficacy, and costs of delivering this intervention in local community hospitals. Through detailed process analysis, based on Diffusion Theory and Organizational Innovation Theory, we will assess program feasibility, participant and staff reactions to the program and the likelihood of program continuation in the community after the funding period. Cost analysis will be conducted to examine the costs of program implementation and payment mechanisms in the community setting.
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0.948 |
1993 — 2004 |
Lerman, Caryn |
M01Activity Code Description: An award made to an institution solely for the support of a General Clinical Research Center where scientists conduct studies on a wide range of human diseases using the full spectrum of the biomedical sciences. Costs underwritten by these grants include those for renovation, for operational expenses such as staff salaries, equipment, and supplies, and for hospitalization. A General Clinical Research Center is a discrete unit of research beds separated from the general care wards. R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Biobehavioral Lung Cancer Prevention Program |
1 |
1993 — 1995 |
Lerman, Caryn |
K07Activity Code Description: To create and encourage a stimulating approach to disease curricula that will attract high quality students, foster academic career development of promising young teacher-investigators, develop and implement excellent multidisciplinary curricula through interchange of ideas and enable the grantee institution to strengthen its existing teaching program. |
Preventive Oncology Academic Award
Basic science investigations have identified an increasingly large number of genetic factors important in cancer. By communicating this genetic information to high risk individuals, we can facilitate informed decision- making about participation in cancer prevention and early detection programs. The purpose of the proposed program is to improve adherence to cancer control regimens among persons with a genetic susceptibility to develop cancer. Subjects for the primary project will be 750 women aged 40-65 who have a positive family history of breast cancer in at least one first-degree relative. A randomized factorial design will be used to evaluate the impact of Breast Cancer Risk Counseling (BCRC), a form of genetic counseling for women at high risk for breast cancer. In addition, two different styles of presenting cancer control recommendations in BCRC will be tested. The BCRC intervention will be based on the traditional medical genetics counseling model, but will concentrate on breast cancer surveillance, rather than on reproductive decisions. Telephone interviews will be conducted prior to the interventions to collect familial and medical data to calculate individualized breast cancer risks and to assess baseline risk perceptions, psychosocial functioning, and breast screening patterns. Post-intervention and follow-up surveys will be used to assess the short- and long-term impact of the interventions on these outcomes. Also, subgroups of women who are most and least likely to benefit from the different BCRC interventions will be identified, based on their precounseling psychosocial characteristics and demographic backgrounds. The information obtained from this primary project will lay the foundation for other studies to improve adherence to cancer control practices in diverse high-risk populations. The interventions proposed for these studies are replicable, and, if effective, can be administered by nurses and physicians in medical practice.
|
0.948 |
1994 — 1996 |
Lerman, Caryn |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Comparing Models of Pretest Education For Brca1 Testing
DESCRIPTION: (From the applicant's abstract) News of the discovery of BRCA1 is likely to generate strong pressures for clinical testing from biotechnology companies, the medical community, and the public. Our research shows that there currently is a high level of interest in BRCA1 testing among first-degree relatives (FDRs) of breast and ovarian cancer patients. This is despite the fact that only a small percentage of these FDRs will have a predisposing mutation. The results also show that a majority of FDRs have exaggerated sense of their personal risk, high levels of cancer anxiety, and misunderstanding about the benefits and limitations of BRCA1 testing. These findings underscore the importance of developing effective and culturally- sensitive strategies for educating women with a family history who express initial interest in BRCA1 testing. To address this, we have developed two protocols for providing pre-test education to FDRs who may seek BRCA1 testing in the future: 1) Standard Education that addresses the benefits, limitations, and risks of testing, and 2) Education plus Counseling that also addresses the psychosocial aspects of alternate testing decisions. The specific aims of this research are to: 1) evaluate the relative impact of these pre-test education protocols on knowledge and attitudes about BRCA1 testing, testing plans and decisions, psychological well-being, and health behavior; 2) identify women most and least likely to benefit, based on the ethnicity, risk status, and coping styles; and 3) determine the mechanisms by which pre-test education contributes to improved outcomes. The subjects will be 900 African-American and white women with a family history of breast or ovarian cancer. They will be randomized to one of three study conditions: 1) Standard Education only; 2) Education plus Counseling; or 3) Wait-list Control (the wait-list control group will be re-randomized to E or E+C after the 1-month follow-up). lnterventions will be delivered during a 1.5 hour individual visit with a nurse educator. Telephone interviews will be conducted at baseline to collect data on sociodemographics, risk factors, and coping styles (information seeking vs. avoidance), and to establish baseline levels of outcome variables. Follow-up interviews will be conducted 1 and 12 months post-intervention to assess the short and long-term impact of the pre- test education interventions. Causal (path) modelling will be used to identify key variables and causal processes associated with changes in knowledge, attitudes, testing plans, and psychological well-being. The pre- test education interventions are to be replicable and exportable to diverse practice settings where women may seek BRCA1 testing in the future.
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0.948 |
1997 — 1999 |
Lerman, Caryn |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Decisions &Outcomes of Brca 1/2 Test For Breast Patient
The investigators propose a prospective, longitudinal study to examine decision-making about pre-surgery BRCA1/2 testing and the medical, psychosocial, and economic outcomes of testing among newly-diagnosed breast cancer patients who are at high risk for having a BRCA1/2 mutation. The theoretical framework for this investigation is derived from Expected Utility Theory. The Specific aims are (1) to establish rates of uptake of the BRCA1/2 testing prior to surgical treatment for breast cancer and to identify the determinants of the decision to be tested; (2) to evaluate the impact of BRCA1/2 testing on patients' surgical treatment choices; (3) to evaluate the impact of pre-surgery BRTCA1/2 testing on psychological well-being; and (4) to develop a model to estimate the costs of BRCA1/2 testing for newly-diagnosed breast cancer patients per quality-adjusted life years saved. The subjects in this prospective longitudinal study are 400 newly diagnosed breast cancer patients who have an equal to or greater than 25 percent prior probability of having a BRCA1/2 mutation. A baseline assessment will be conducted prior to the offer of testing to collect data on background/controlling variables (sociodemographics, medical, physician and family factors), predictor/moderator variables (preferences for health outcomes, coping style, anxiety, social support), and baseline levels of outcome variables (psychosocial well being, prevention and surveillance practices). Following pre-test education and informed consent, patients will have an opportunity to have BRCA1/2 testing and receive their result during an individual session with a genetic counselor. Follow-up interviews will be conducted at 1-, 6-, 12-, and 18-months post-surgery to collect outcome data. The primary group comparisons in multiple regression models will be between BRCA1/2 carriers, non carriers, and pre-surgery test decliners. The proposed cost-effectiveness analysis will incorporate prospective data on patient preferences and outcomes together with secondary data from the literature, into a decision-analytic model.
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0.948 |
1998 — 1999 |
Lerman, Caryn |
U24Activity Code Description: To support research projects contributing to improvement of the capability of resources to serve biomedical research. |
Cancer Genetics Network
DESCRIPTION: (Applicant's Description) While advances in cancer genetics are occurring at rapid pace, critical questions about genetic susceptibility and prevention remain unanswered. In response to the RFA for the Cancer Genetics Network, we propose to: (1) Enroll substantial numbers of the following populations into the CGN: (a) hereditary breast, ovarian, and colon cancer families, (b) newly diagnosed high risk breast cancer patients, and (c) persons at low to moderate risk of cancer; (2) Utilize our existing networks of community-based hospitals and primary care clinics to increase CGN enrollment of African Americans and Latin Americans in the Washington, D.C. area; (3) Contribute our well-validated IRB-approved protocols for informed consent, pre-test education, and genetic counseling to the CGN; (4) Provide CGN investigators with access to our state-of-the-art laboratory technologies for diagnostic genetic analysis; (5) Utilize our existing infrastructure for cancer DNA/tissue collection, processing, and storage to contribute to basic cancer genetics research in the CGN; (6) Modify existing cancer genetics educational materials to target African Americans and develop Spanish language materials, consent forms and counseling protocols for use with Latin Americans; (7) Provide genetics education and training programs for a wide range of healthcare providers, including nurses and medical students; and (8) Contribute our expertise conducting research on the clinical, psychosocial, and economic outcomes of genetic testing for cancer susceptibility.
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0.948 |
1998 — 1999 |
Lerman, Caryn |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Comparing Models of Counseling For Brca1/2 Testing |
0.948 |
1999 — 2008 |
Lerman, Caryn |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Transdisciplinary Tobacco Use Research Centers @ University of Pennsylvania |
1 |
1999 — 2002 |
Lerman, Caryn |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Biobehavioral Predictors of the Efficacy of Nicotine Replacement Therapy
Transdermal nicotine patch (TN) has been shown to boost quit rates above those achieved with behavioral counseling alone, yet the majority of smokers do not maintain abstinence. A nicotine nasal spray (NS) with reinforcing properties more similar to smoking has been approved for clinical use, and has shown success rates at least comparable to TN. Because of possible irritant effects of NS, it may not be the preferred treatment for all smokers. To date there have been no empirically validated methods to match smokers to a particular treatment. We believe that smokers who derive greater positive reinforcement from smoking will benefit more from NS versus TN., and further, that such smokers can be identified by their genotypes for genes important in dopamine regulation. As an extension of our ongoing research on dopamine genes and smoking, we propose to evaluate whether genetic and non-genetic factors can be used to predict the relative efficacy of NS versus TN. Further, we will explore whether the effects of genotype on smoking cessation are mediated by nicotine replacement and/or by heritable personality traits. In the proposed randomized clinical trial, smokers will receive behavioral counseling plus either NS or TN. After initial eligibility screening, subjects will complete a pretreatment assessment of smoking related and psychological variables and have blood drawn for genotyping and cotinine analysis. NS and TN will be delivered over an 8 week treatment period. All subjects will also participate in 8 1.5 sessions of group behavioral counseling. mediating outcomes will be assessment at pretreatment (e.g., smoking reinforcement, novelty-seeking personality) and prior to subsequent treatment visits (e.g., mood, withdrawal). Smoking outcomes will be assessed prior to each treatment visit and at 8 weeks, 6 months, and 12 months after the target quit data (biochemically verified). The overall goal of this research is to increase our understanding of the role of genetic and psychological factors in response to NRT. Further, we will learn more about why people fail to quit smoking by studying the bio-behavioral mechanisms of genetic effects. The ultimate objective is to provide information necessary to tailor smoking treatment with NS versus TN to individual smokers' needs.
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0.948 |
2003 — 2007 |
Lerman, Caryn |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Pharmacogenetic Investigation of Naltrexone @ University of Pennsylvania
DESCRIPTION (provided by applicant): Several converging lines of evidence support the role of the endogenous opioid system in the reinforcing effects of nicotine; however, the efficacy of opioid antagonists (e.g., naltrexone, NTX) for the treatment of tobacco dependence remains unresolved. The results of clinical studies of NTX for tobacco dependence are inconsistent, which may reflect individual differences in drug response. Rather than concluding that NTX is an ineffective treatment for tobacco dependence, research is needed to identify those smokers for whom NTX will have the strongest beneficial effects on smoking behavior. Therefore, the specific goal of the proposed research is to test whether genetic variation in the functional mu-opioid receptor gene predicts the effects of NTX on cigarette smoking and nicotine reinforcement. Based on preclinical animal and human research, we hypothesize that smokers with the OPRM1 Asp40 variant will be more likely to respond to NTX compared to placebo (PLA), as reflected in reduced cigarette smoking and lower levels of nicotine reinforcement. This hypothesis will be tested using two within-subject behavioral pharmacology paradigms in which NTX 50mg and PLA will be administered to smokers who have been genotyped for OPRM1. The first experiment will examine the effects of NTX on the risk of relapse following an initial smoking lapse, using the validated experimental model of relapse designed by Stitzer and colleagues. Following 3 days of NTX (or PLA) and verified smoking abstinence, 70 smokers (35 from each genotype group) will be exposed to a "programmed" smoking lapse, and then monitored for three days in their natural environments. Following a 5-day wash-out period, the sequence will be repeated with NTX or PLA (order of medications counterbalanced). The primary outcomes are cigarette smoking and nicotine levels following the lapse episode. While such ad-libitum smoking experiments are more naturalistic, these designs can't disentangle the effects of a medication on the reinforcing value of nicotine from effects on the reinforcing value of smoking (including conditioned reinforcers). Therefore, the second experiment will examine the effects of NTX (vs. PLA) on the reinforcing value of nicotine, using a validated cigarette choice paradigm, developed by Perkins and colleagues. In this experiment 80 smokers genotyped for OPRM1 (40 from each genotype group) will receive acute pre-treatment with NTX 50mg or PLA following overnight abstinence, and before they participate in the cigarette choice procedure. The primary outcome will be the number of puffs taken from a 0.6 mg nicotine cigarette versus a 0.05 (denicotinized) cigarette during a 3-hour period. Following a washout period, the sequence will be repeated (with NTX or PLA). The long-term objective of this research is to discover and develop new pharmacogenetic treatment models that can be readily translated to the clinical setting to individualize pharmacotherapy and maximize effectiveness.
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1 |
2004 |
Lerman, Caryn |
M01Activity Code Description: An award made to an institution solely for the support of a General Clinical Research Center where scientists conduct studies on a wide range of human diseases using the full spectrum of the biomedical sciences. Costs underwritten by these grants include those for renovation, for operational expenses such as staff salaries, equipment, and supplies, and for hospitalization. A General Clinical Research Center is a discrete unit of research beds separated from the general care wards. |
Bio-Behavioral Predictors of the Efficacy of Nicotine Replacement Therapy @ University of Pennsylvania
nicotine replacement; smoking cessation; behavior prediction; human therapy evaluation; transdermal drug delivery; inhalation drug administration; patient oriented research; behavioral /social science research tag; human subject; clinical research;
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1 |
2004 |
Lerman, Caryn |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Core a: Administrative Core @ University of Pennsylvania |
1 |
2004 — 2008 |
Lerman, Caryn |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Efficacy of Extended Patch Treatment by Oprm1 Genotype @ University of Pennsylvania
Based on preclinical data on nicotine-opioid system interactions and preliminary data from the original project, the current application proposes to evaluate whether genetic variation in the mu opioid receptor (OPRM1 ) predicts response to standard versus extended transdermal nicotine (TN) therapy. The OPRM1 Asp40 variant increases the binding affinity of beta-endorphin for this receptor by three-fold, relative to the wild-type Asn40 OPRM1. Since nicotine increases release of beta-endorphin, we hypothesized in the original project that smokers with the OPRMI Asp40 variant would have better outcomes with NRT. The results showed that smokers carrying the OPRMl Asp40 variant were significantly more likely than those homozygous for the Asn40 variant to be abstinent at the end of TN treatment. Moreover, the differential treatment response was most pronounced during the 21 mg dose phase of TN, reduced as TN was tapered, and was no longer present after treatment was discontinued. We propose to replicate and extend these findings by conducting randomized placebo-controlled trial to determine the effects of standard treatment (ST) versus extended treatment (ET) with TN among smokers genotyped for the OPRMI Asn40Asp variant. Equal numbers of smokers with the Asn40 (n=300) and Asp40 (n=300) variants will be randomized to receive either standard treatment with TN (21 mg x 4 weeks, 14mg x 2 weeks, 7 mg x 2 weeks, placebo x 16 weeks) or extended treatment with TN (21 mg x 20 weeks, 14mg x 2 weeks, 7 mg x 2 weeks). The primary outcome will be biochemically verified 7-day point prevalence abstinence from smoking at 20 weeks (end of 21mg dose phase of treatment). Secondary outcomes include logitudinal smoking phenotypes and abstinence symptoms. The ultimate objective of this research is to identify smokers who benefit from extended TN treatment based on genetic information.
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1 |
2005 |
Lerman, Caryn |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Pharmacogenetic Investigation of Naltrexone (Rmi) @ University of Pennsylvania
DESCRIPTION (provided by applicant): Several converging lines of evidence support the role of the endogenous opioid system in the reinforcing effects of nicotine; however, the efficacy of opioid antagonists (e.g., naltrexone, NTX) for the treatment of tobacco dependence remains unresolved. The results of clinical studies of NTX for tobacco dependence are inconsistent, which may reflect individual differences in drug response. Rather than concluding that NTX is an ineffective treatment for tobacco dependence, research is needed to identify those smokers for whom NTX will have the strongest beneficial effects on smoking behavior. Therefore, the specific goal of the proposed research is to test whether genetic variation in the functional mu-opioid receptor gene predicts the effects of NTX on cigarette smoking and nicotine reinforcement. Based on preclinical animal and human research, we hypothesize that smokers with the OPRM1 Asp40 variant will be more likely to respond to NTX compared to placebo (PLA), as reflected in reduced cigarette smoking and lower levels of nicotine reinforcement. This hypothesis will be tested using two within-subject behavioral pharmacology paradigms in which NTX 50mg and PLA will be administered to smokers who have been genotyped for OPRM1. The first experiment will examine the effects of NTX on the risk of relapse following an initial smoking lapse, using the validated experimental model of relapse designed by Stitzer and colleagues. Following 3 days of NTX (or PLA) and verified smoking abstinence, 70 smokers (35 from each genotype group) will be exposed to a "programmed" smoking lapse, and then monitored for three days in their natural environments. Following a 5-day wash-out period, the sequence will be repeated with NTX or PLA (order of medications counterbalanced). The primary outcomes are cigarette smoking and nicotine levels following the lapse episode. While such ad-libitum smoking experiments are more naturalistic, these designs can't disentangle the effects of a medication on the reinforcing value of nicotine from effects on the reinforcing value of smoking (including conditioned reinforcers). Therefore, the second experiment will examine the effects of NTX (vs. PLA) on the reinforcing value of nicotine, using a validated cigarette choice paradigm, developed by Perkins and colleagues. In this experiment 80 smokers genotyped for OPRM1 (40 from each genotype group) will receive acute pre-treatment with NTX 50mg or PLA following overnight abstinence, and before they participate in the cigarette choice procedure. The primary outcome will be the number of puffs taken from a 0.6 mg nicotine cigarette versus a 0.05 (denicotinized) cigarette during a 3-hour period. Following a washout period, the sequence will be repeated (with NTX or PLA). The long-term objective of this research is to discover and develop new pharmacogenetic treatment models that can be readily translated to the clinical setting to individualize pharmacotherapy and maximize effectiveness.
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1 |
2008 — 2012 |
Cappella, Joseph Nicholas (co-PI) [⬀] Lerman, Caryn |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Smoking Cues in Anti-Tobacco Psas @ University of Pennsylvania
PROJECT TITLE: Project # 2: Smoking Cues in Anti-tobacco PSAs PRINCIPAL INVESTIGATORS: Caryn Lerman, Ph.D., Joseph N. Cappella, Ph.D. KEY PERSONNEL: Lerman (15%), Cappella (10%), Andrew Strasser, Ph.D. (15%), E. Paul Wileyto, Ph.D. (10%), Chris Jepson (5%). PROJECT SUMMARY: Tobacco use is the greatest preventable cause of death worldwide yet about 1 in 5 adults in the U.S. continue to smoke. Message campaigns, such as public service announcements (PSAs), designed to increase the awareness of the health harms of tobacco use, have shown initial promising findings. This has led to exploration of the features of anti-tobacco PSAs that are most and least persuasive, including types of appeals and PSA components or features. Anti-smoking mass media campaigns often present smoking-related cues (e.g., seeing someone smoke) to illustrate the negative consequences of smoking). However, these smoking-related "cues" can elicit strong smoking urges, providing a key motivation for continued smoking in the face of a desire to quit. Our preliminary research shows that when chronic smokers view anti-smoking PSAs that include smoking cues, their urges to smoke increase significantly - if the central argument of the PSA is weak. To extend this research, we propose to study the effects of smoking cues in anti-tobacco PSAs on smoking urges, message processing, persuasion, and smoking behavior in a sample of 300 chronic smoking adults. This laboratory-based study will use a 3 (smoking cue: no cue/peripheral cue/central cue) x 2 (low/high argument strength) factorial (between-subject) design. PSAs in different conditions will be balanced for multiple explicit and implicit ad features. The primary outcomes are: 1) smoking urges, 2) message processing (recall, perceived ad effectiveness), and 3) persuasion (attitudes, self-efficacy, intentions). In addition, participants will be monitored for physiological arousal (heart rate, skin conductance) elicited during cue presentation. Following the session, we will permit participants to smoke in the smoking research laboratory and assess latency and consumption, thus serving as a behavioral measure of PSA smoking cue effects. Results from this study may importantly provide empirical support for better development of anti-smoking PSAs, and to support restrictions on tobacco industry adver
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1 |
2008 — 2013 |
Blendy, Julie (co-PI) [⬀] Lerman, Caryn |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Administrative Core @ University of Pennsylvania
The Administrative Core of the CIRNA will: (1) monitor and evaluate the progress of the CIRNA, by coordinating the activities of the executive committee and the advisory board;(2) enhance interdisciplinary education of CIRNA trainees and faculty, by coordinating seminars and workshops, and by distributing articles of relevance;(3) enhance interdisciplinary communication among CIRNA investigators and enhance synergy across CIRNA components by coordinating formal and informal meetings among project/core investigators, and maintaining an intranet site and list-serve; (4) facilitate the developmental research program (with the Career Development Core), which solicits and funds promising developmental proposals by trainees and junior faculty;(5) support the CIRNA as a national resource, by providing access to results of CIRNA research and educational information, and by implementing a comprehensive data sharing policy;and (6) provide administrative and budgetary oversight for the CIRNA. Drs. Lerman and Blendy will co-lead the CIRNA and its Administrative Core, with responsibilities based on complementary expertise in preclinical research (Blendy) and clinical research (Lerman).
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1 |
2009 — 2010 |
Blendy, Julie Ann (co-PI) [⬀] Lerman, Caryn Liu-Chen, Lee-Yuan (co-PI) [⬀] Zubieta, Jon-Kar (co-PI) [⬀] |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Functional Characterization of Oprm1 A118g in Nicotine Dependence @ University of Pennsylvania
DESCRIPTION (provided by applicant): A substantial body of evidence implicates the endogenous opioid system, and the mu opioid receptor (MOR) in particular, in the reinforcing effects of drugs of abuse, including nicotine. A single nucleotide polymorphism (SNP) in the mu opioid receptor gene (OPRM1 Asp40) is associated with the ability to quit smoking, as well as nicotine reward and withdrawal symptoms. However, the precise mechanism through which this SNP influences nicotine dependence remains unresolved. In this R21 application, we propose a translational cross-species approach to elucidate the functional significance of the OPRM1 Asp40 variant in the neurobiology of nicotine dependence. Toward this end, we have developed a knock-in mouse that possesses the mouse equivalent of the Asp40 in the Oprm1 gene (Asp38), and we provide compelling preliminary evidence for functional significance. Understanding whether this variant alters MOR binding in response to nicotine in mice and in human smokers will improve our understanding of genotype by nicotine interactions, and will provide a critical first step toward elucidating the neurobehavioral mechanisms through which this SNP alters smoking behavior. The proposed mice experiments will: 1) determine if the mouse Asp38 alters basal or nicotine-stimulated changes in MOR binding and signaling throughout the brain using [3H]carfentanil and autoradiography;and 2) evaluate the effect of the Asp38 variant on behavioral responses to nicotine using conditioned place preference and nicotine-primed re-instatement paradigms. The human experiment will use [11C]carfentanil PET imaging to assess the effects of intravenous (IV) nicotine versus saline (within-subject) on MOR binding potential in 24 chronic smokers genotyped prospectively and stratified by OPRM1 genotype. These experiments will establish a translational cross-species model for functional characterization of genetic variants, and will elucidate the neurobiology of nicotine dependence, a significant public health problem. PUBLIC HEALTH RELEVANCE: The proposed experiments in mice and humans will help us understand the mechanisms by which a specific gene variant (OPRM1 A118G) is associated with nicotine dependence.
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1 |
2009 — 2013 |
Lerman, Caryn |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Center For Interdisciplinary Research On Nicotine Addiction (Cirna) @ University of Pennsylvania
DESCRIPTION (provided by applicant): Abstinence from smoking produces aversive symptoms that prompt relapse, often within the first week following a quit attempt. Clarifying the neurobiological and behavioral underpinnings of these early abstinence symptoms is, therefore, critical to develop more efficacious treatments. The proposed Center for Interdisciplinary Research on Nicotine Addiction (CIRNA) extends nine years of research conducted in the Transdisciplinary Tobacco Use Research Center (TTURC) at UPENN. Spanning from preclinical to clinical studies, CIRNA includes a highly interactive set of projects and cores that seek to: (1) discover the cellular, molecular, neural, and behavioral basis of early nicotine abstinence effects that contribute to relapse;(2) identify brain and behavioral mechanisms through which efficacious therapies modulate these processes;and (3) validate novel medication screening approaches. Project 1 uses neurobiology and pharmacology to elucidate the molecular and behavioral basis of emotional and cognitive symptoms of nicotine abstinence and re-exposure in a mouse model. Project 2 uses electrophysiology and pharmacology to explore the effects of nicotine abstinence and re-exposure on sensory processing in key brain regions in mice. Project 3 uses human neuroimaging to examine the neural substrates of early abstinence symptoms and medication response. Project 4 extends this work by validating novel approaches to improve the sensitivity of early human medication screening paradigms for nicotine dependence. Shared resources, including an Administrative Core, a Data Management and Biostatistics Core, and a Biospecimen Core provide value-added, as well as support for a comprehensive data sharing plan. A Career Development Core promotes involvement of post-doctoral fellows and junior investigators in these projects, and supports pilot projects to facilitate career development. Thus, the CIRNA addresses the clinically important problem of nicotine dependence using innovative multidisciplinary approaches, with the ultimate goal of developing more efficacious medications for tobacco dependence and prevention of tobacco-related disease. The CIRNA is proposed to replace the TTURC, since this NIH initiative is ending. CENTER CHARACTERISTICS
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1 |
2009 — 2011 |
Lerman, Caryn Loughead, James |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Neural Substrates of Cognitive Deficits in Nicotine Withdrawal @ University of Pennsylvania
DESCRIPTION (provided by applicant): In chronic smokers, abstinence from nicotine produces cognitive deficits that prompt relapse. Understanding the mechanisms that underlie these abstinence symptoms is critical to develop better treatments for nicotine addiction. The proposed project is designed to identify the brain mechanisms that underlie abstinence- induced cognitive symptoms in smokers using an integrated approach that combines neuroimaging, pharmacology, and genetics. We focus on the functional catechol-O-methyltransferase COMT (val158met) polymorphism, which has been implicated in both nicotine dependence and cognitive function. We have completed a pilot BOLD fMRI study which shows that smokers homozygous for the high activity val allele are more sensitive to the effects of an abstinence challenge on measures of cognition and brain function. This 3-year R01 application is designed to: (a) replicate and extend these results in a larger sample, and (b) perform a critical proof of mechanism experiment that tests the effects of the COMT inhibitor tolcapone on cognitive performance and brain function in abstinent smokers stratified by COMT val158met genotype. Specifically, we propose a within-subject double-blind cross-over neuroimaging study of short-term (13 days) tolcapone (vs. placebo) administration. Forty chronic smokers (20 with val/val genotypes and 20 with met/met genotypes) will undergo BOLD fMRI during 2 medication periods while performing a working memory task (N-back Task) and a sustained attention task (Continuous Performance Task): 1) after 3 days of monitored abstinence while on tolcapone, and 2) after 3 days of monitored abstinence while on placebo (medication order counterbalanced with a 2-week washout). A pre-treatment (baseline) scan is included to compare outcomes while smoking as usual to those while abstinent (on placebo). The primary outcome is medication effects (within subject) on task-related BOLD activation after 3 days of abstinence. Changes in behavioral performance and subjective symptoms will be examined in relation to brain activity changes. The proposed study will provide a critical mechanistic understanding of the role of COMT in nicotine dependence, thereby facilitating development of novel medications. Data generated from this study may further establish cognitive performance measures as important endophenotypes for nicotine dependence. PUBLIC HEALTH RELEVANCE: This study will improve our understanding of the brain mechanisms that underlie abstinence-induced cognitive deficits which promote smoking relapse.
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1 |
2009 — 2013 |
Lerman, Caryn |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Neuroimaging Abstinence and Medication Response @ University of Pennsylvania
Abstinence from smoking produces aversive symptoms that prompt relapse, often within the first week following a quit attempt. Our prior work has characterized these nicotine abstinence symptoms in smoking cessation pharmacotherapy trials and identified those relating to smoking relapse. Extending this work, we propose to elucidate brain and behavioral mechanisms underlying medication effects on key early abstinence symptoms using arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI), and blood oxygen level dependent (BOLD) functional MRI (fMRI). Varenicline, an a4p2 nicotinic acetylcholine receptor partial agonist, will be used as a model medication, based on its superior clinical efficacy. The specific aims are: (1) to identify the neural substrates for varenicline effects on urges to smoke, using ASL perfusion MRI during a nicotine abstinent resting state, (2) To identify the neural substrates for varenicline effects on working memory during nicotine abstinence, using the N-back paradigm, and (3) To identify the neural substrates for varenicline effects on limbic reactivity to emotional stimuli during nicotine abstinence using a Face Emotion Identification fMRI paradigm. The study design is a within-subject double-blind crossover neuroimaging study of short-term (13 days) varenicline (vs. placebo) administration. Sixty treatmentseeking smokers will be scanned during 2 medication periods: (1) after 3 days of monitored abstinence while on varenicline, and (2) after 3 days of monitored abstinence while on placebo (medication order counterbalanced with a 2-week washout period). The primary outcomes are medication effects (within subject) on: (a) resting regional cerebral blood flow (rCBF) (ASL perfusion MRI), and (b) task-related BOLD activation (BOLD fMRI) after 3 days of abstinence. We will examine changes in behavioral performance and subjective symptoms in relation to brain activity changes. Following this investigation, all participants will be enrolled into a 12 week open-label varenicline trial, and we will explore associations of imaging data with clinical relapse. This research will contribute to pharmacotherapy development for nicotine dependence by: (a) providing a "neural fingerprint" against which future novel compounds can be compared, and (b) establishing the use neuroimaging as an early "surrogate marker" for medication response.
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1 |
2009 — 2010 |
Lerman, Caryn Loughead, James |
R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Nicotine Abstinence-Induced Cognitive Alterations by Comt Genotype @ University of Pennsylvania
DESCRIPTION (provided by applicant): In chronic smokers, abstinence from nicotine produces aversive cognitive symptoms which predict relapse. Understanding the genetic and neural mechanisms that underlie these abstinence-induced cognitive deficits is therefore critical to develop more efficacious treatments for nicotine addiction. The overall goal of this R03 application is to examine whether genetic variation in catechol-O-methyltransferase (COMT val158met polymorphism) is associated with adverse cognitive effects of nicotine abstinence in chronic smokers. COMT is a methylation enzyme that degrades dopamine and regulates dopamine levels in the frontal cortex. The COMT gene has a common functional polymorphism (val158met);the val allele is associated with an increase in COMT enzyme activity and a decrease in brain dopamine levels. Importantly, research by our group and others has linked the COMT val allele with nicotine dependence and smoking relapse. New data from our laboratory suggest that the increased smoking relapse risk in COMT val allele carriers may be attributable to an exacerbation of cognitive deficits during nicotine abstinence in this subgroup of smokers. However, this initial study was small and was limited to assessment of working memory. Given the validated relationship of this polymorphism with smoking relapse, a larger and broader examination of the role of COMT val158met in abstinence-induced cognitive function is clearly needed. Toward this end, we propose to examine the association of COMT val158met with cognition and brain function using a nicotine abstinence challenge laboratory paradigm validated in our prior work. Forty eligible smokers (20 met/met and 20 val/val) will participate in two blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) sessions occurring 1-2 weeks apart in counterbalanced order: smoking as usual vs. overnight (= 14 hours) abstinent. BOLD fMRI will be acquired while they perform validated tasks probing key components of executive cognitive function, including sustained attention (continuous performance task;CPT), working memory (N-back), and behavioral inhibition (Go-No-Go). These tasks have been selected based upon their sensitivity to abstinence effects and/or COMT genotype associations. The primary outcomes are task-related BOLD activation and performance during abstinence vs. satiety. Data generated from this study may further establish cognitive measures as important endophenotypes for genetic studies of nicotine dependence. The novel genetics and neuroimaging approach proposed can also be applied in the future to study the role of genetic variation in other drug addiction phenotypes. PUBLIC HEALTH RELEVANCE: This study will improve our understanding of individual differences in cognitive deficits that arise during abstinence from smoking and predict relapse.
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1 |
2009 — 2010 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Abramson Cancer Center of the U of P Core Support Grant @ University of Pennsylvania
The Abramson Cancer Center facilitates interdisciplinary cancer research, education, and patient care. Its 299 members are drawn from 41 Departments and eight Schools of the University and have $120,755,622 million in research and training (annual direct costs), a 73% increase in the past five years, of which $111,281,669 is peer-reviewed and $56,709,782 is NCI funded (138% increase in the past five years). This includes 20 NIH P01s and seven P50s. John Glick, MD, has served as Director since 1985. Eleven Research Programs comprise the Cancer Center's three Divisions (Fundamental Research, Clinical Research, Cancer Control and Population Sciences). The Cancer Center supports 15 Shared Resources, five of which are new. The development of strong Research Programs and leading-edge Shared Resources, the recruitment of outstanding faculty in areas of priority, and the acquisition of additional research space have enabled the Cancer Center to realize its mission. An ongoing strategic planning process identifies future directions, while guiding current activities and resource allocations. A wide range of seminars and retreats as well as interdisciplinary laboratory space are among the ways in which the Cancer Center sucessfully facilitates interaction and collaboration. Developmental Funds are critical to faculty recruitment and the funding of innovative pilot projects with the potential for peer-reviewed funding, translational research initiatives, and Shared Resources. The Division of Cancer Control and Population Sciences has benefited from the recruitment of Caryn Lerman, PhD, as Associate Director and other significant faculty recruitments. The Clinical Research Division's progress is distinguished by innovative translational research in all Research Programs and a nationally recognized experimental therapeutics effort. In the basic sciences, leadership changes have led to greater activity in translational research and increased collaborations. The Cancer Center continues to meet Comprehensiveness guidelines, and was last approved in 1999.
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1 |
2010 — 2011 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Abramson Cancer Center Support Grant @ University of Pennsylvania
DESCRIPTION (provided by applicant): The Abramson Cancer Center (ACC) of the University of Pennsylvania was founded in 1973 and was one of the first Comprehensive Cancer Centers designated by the National Cancer Institute (NCI). Since its inception, the ACC has been continuously funded through the NCI CCSG. The ACC is a matrix center that facilitates transdisciplinary cancer research, education, and patient care. Its 318 members are drawn from 37 Departments and 8 Schools of the University and have $168,806,933 in research and training funding (annual direct costs), a 40% increase since 2004. Of these funds, $156,713,965 is peer-reviewed and $51,462,763 is NCI funded, this funding includes 16 NIH P01s, 5 P50s, 3 P30s, and 1 P20. Commensurate with the growth in funding, the ACC has more than doubled its assigned space since 2004 with the opening of the Perelman Center for Advanced Medicine, the Roberts Proton Therapy Facility, and the Fisher and Colket Translational Research Buildings. Through the development of integrated programs of laboratory, clinical, and population-based research, the ACC seeks to foster pioneering scientific discoveries that can be translated into new methods for cancer prevention, detection, and treatment. Currently, there are 11 multidisciplinary research programs in the ACC: Immunobiology, Tumor Biology, Tumor Virology, Cancer Therapeutics, Pediatric Oncology, Radiobiology and Imaging, Melanoma and Cutaneous Malignancies, Hematologic Malignancies, Breast Cancer, Tobacco and Environmental Carcinogenesis, and Cancer Control. The Cancer Center supports 13 Shared Resources, of which 2 are new and 2 have been restructured. The continuous development of strong Research Programs and leading-edge Shared Resources, the recruitment of outstanding faculty, and the acquisition of additional research space allow the ACC to support the research activities of its members. An ongoing strategic planning/implementation process allows the ACC to identify emerging cancer research areas for future development, while guiding current activities and resource allocations. The ACC supports a wide range of seminars and retreats and promotes interdisciplinary use of research space to facilitate interaction and collaboration among its members. Developmental funds remain critical for the support of faculty recruitment and the funding of innovative pilot projects with the potential for peer-reviewed funding and translation. The ACC has an engaged leadership focused on supporting the transdisciplinary cancer research of its productive membership.
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1 |
2010 — 2014 |
Lerman, Caryn Tyndale, Rachel Fynvola (co-PI) [⬀] |
U01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Pharmacogenetics of Nicotine Addiction Treatment @ University of Pennsylvania
DESCRIPTION (provided by applicant): Smoking is a significant public health problem, and there is a great need for research to improve smoking cessation treatment outcomes. The goal of the Pharmacogenetics of Nicotine Addiction Treatment (PNAT) research program is to generate the evidence base to optimize treatment decisions for Individuals who want to quit smoking. During the past 4 years of PNAT1, we have characterized genetic variants altering nicotine pharmacokinetics as well as pharmacodynamic genetic variants influencing response to pharmacotherapies for smoking cessation treatment. We have shown that the CYP2A6 enzyme is critical in the metabolic inactivation of nicotine, and inherited variation in nicotine clearance influences smoking behavior and cessation. With a vision toward translation of our research to practice, we have characterized a genetically-informed biomarker of CYP2A6 activity, specifically the nicotine metabolite ratio (NMR;3'hydroxycotinine/cotinine), which reflects both genetic and environmental influences on CYP2A6 activity and nicotine clearance. The NMR is measured noninvasively in smokers with established reliability, stability, analytic validity, and efficacy as a predictor of therapeutic response in multiple independent (retrospective) clinical trials. Translation of these findings to clinical practice, the ultimate goal of the PGRN, requires validation In a prospective stratified clinical trial comparing alternative therapies for smoking cessation. In this competing renewal, we propose to conduct a prospective placebo-controlled multi-center pharmacogenetic (PGx) clinical trial of alternative therapies for smoking cessation treatment in 1,350 smokers. Randomization to placebo, transdermal nicotine, or varenicline will be stratified prospectively based on the NMR, the most robust genetically-informed biomarker for smoking cessation identified to date. Further, to facilitate translation to practice, we will determine the cost-effectiveness of our proposed PGx approach using both primary data and simulation models. In addition to these goals, we propose within this UOI to: identify additional sources of genetic variation in nicotine clearance and the NMR;investigate additional pharmacokinetic and pharmacodynamic gene associations with therapeutic response biomarker;and elucidate the mechanisms involved in identified PGx effects on smoking cessation. The proposed research provides the next critical step to validate a genetically-informed diagnostic tool, the NMR, which clinicians can use in the future to optimize treatment decisions for their patients who wish to quit smoking. As outlined recently by NIDA, due to the devastating health consequences of smoking and the urgent demand for better treatments, the validation of biomarker strategies to improve the outcomes of treatments a major public health priority. RELEVANCE: The ultimate goal of this research is to validate a genetically-informed diagnostic tool which clinicians can use in the future to optimize treatment decisions for their patients who smoke. Due to the enormous adverse impact of tobacco use, this research has high public health significance.
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1 |
2010 — 2011 |
Lerman, Caryn |
U01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
University of Pennsylvania (Upenn) Overall Coordinating &Clinical Trial Site @ University of Pennsylvania
Clinical Trials; Pennsylvania; Site; Universities
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1 |
2010 — 2014 |
Kurtz, Matthew M (co-PI) [⬀] Lerman, Caryn |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Cognitive Training For Nicotine Dependence @ University of Pennsylvania
PROJECT SUMMARY Cognitive impairment is commonly reported by smokers attempting to quit. Such symptoms prompt relapse to smoking, perhaps to ameliorate these deficits and restore functioning to pre-cessation levels. Indeed, objectively assessed cognitive impairment increases risk of smoking relapse, supporting the premise that withdrawal-related cognitive impairment is an important therapeutic target to aid in smoking cessation. The proposed randomized clinical trial will evaluate a cognitive remediation training (CRT) intervention to ameliorate abstinence-induced cognitive impairment and improve quitting success in treatment-seeking smokers. Specifically, we will evaluate whether computer-assisted CRT improves quitting success with nicotine patch therapy, the most widely used medication for smoking cessation in the U.S. Three hundred and forty smokers will receive nicotine patch therapy, plus either: (a) computer-assisted CRT or (b) a cognitive stimulation control (CSC) intervention, based on random assignment. The CRT intervention is a 12-week standardized course (36 hours total) of computerized cognitive exercises designed to buffer smokers against cognitive deficits that increase smoking relapse risk. CSC (control condition) is an active intervention designed to address the non-specific effects of attention and computer stimulation. CRT or CSC will be initiated 4 weeks prior to the target quit date. Standard 8-week open-label nicotine patch therapy will commence on the target quit date for participants in both study conditions. The primary outcome will be biochemically verified point- prevalence abstinence at the 6-month follow-up. Secondary outcomes include end of treatment quit rates, time to relapse, and recovery rate from smoking lapses. Key intermediate endpoints include changes in cognitive performance and brain function (primary), as well as craving, functional status, and adherence. To examine pre- to post-treatment changes in brain function associated with CRT vs. CSC, BOLD fMRI data will be acquired for a subset of participants (n=50) pre- and post-treatment while they complete neurocognitive tasks. Thus, in addition to evaluating the efficacy of a novel CRT intervention, this study will provide a critical mechanistic understanding of the role of cognitive function in smoking relapse.
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Senior Leadership @ University of Pennsylvania
base; Cancer Center; Cancer Center Support Grant; Core Facility; Core Grant; Decision Making; Electronic Mail; Ensure; Feedback; Grant Review Process; Interdisciplinary Study; Leadership; meetings; Process; Research; Resource Sharing; Role; Telephone;
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Cancer Center Administration @ University of Pennsylvania
Cancer Center; Cancer Center Support Grant;
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Planning and Evaluation @ University of Pennsylvania
This year, the Abramson Cancer Center continued its commitment to a continuous, collaborative program planning and evaluation process. Internal planning and evaluation initiatives are carefully defined, with input from the broad Cancer Center membership, so that they can be most effective in achieving the scientific goals and objectives of the Cancer Center. Mechanisms employed by the Cancer Center in its program and planning process are described below.
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Breast Cancer Program @ University of Pennsylvania
The goal of the Program is to further our understanding of the biology of breast cancer and to provide scientific support and rationale for preclinical and clinical efforts to improve the detection, prevention, treatment and outcome of breast cancer. Membership, activities and research accomplishments for each of these groups are described below. Breast Cancer Program members work collaboratively both together and with members of other ACC program within these areas, as demonstrated by the transdisciplinary nature of the majority of projects described below.
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Program Leaders @ University of Pennsylvania
Program leaders seek to support innovation while maintaining a steadfast focus on translational research. The Program currently thrives in a rich and diverse environment that encourages interaction and collaboration. The leadership seeks to provide the core infrastructure necessary to enable the work, and also to invest in key technologies and/or personnel to meet strategic goals.
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Proteomics Core @ University of Pennsylvania
The Proteomics Core is constantly developing new technologies and incorporating state of the art instrumentation to provide the most sensitive proteomics capabilities to ACC members.
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Radiobiology & Imaging Program @ University of Pennsylvania
The goals of the Radiation Biology & Imaging (RBI) Program remain unchanged since the last review of the ACC Core Grant. The RBI program seeks to improve the outcome of patients through the advanced understanding of how ionizing and non-ionizing radiation interacts with cancer and normal tissues. Through the RBI Program, investigators from diverse backgrounds and multiple Departments within the School of Medicine, Veterinary School and the School of Engineering, are brought together to identify the molecular and physiological determinants of radiation and PDT response in tumors. New areas of focus developed in the last two years include the use of nanomaterials to deliver therapeutic and imaging agents to tumors and the use of sophisticated imaging and radiation delivery approaches to better define and evaluate targets and treat tumors with the lowest possible damage to normal tissues. These new efforts have been strengthened with a substantial recruitment effort of new members into the RBI program. The programmatic goals are: 1. to understand the basic molecular mechanisms underlying the cellular response to radiation and to develop molecular targets for manipulating the response of tumors to drugs and ionizing radiation; 2. to develop clinical trials for photodynamic therapy and understand the underlying molecular and physiologic mechanisms that underlie its use; 3. to develop mechanisms to test and validate invasive and non-invasive methods for measuring tumor oxygenation and metabolic status; 4. to study the molecular events in the response to DNA damage by ionizing radiation; and 5. to develop imaging techniques that are related to the delivery and underlying mechanisms of radiation.
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Recruitment, Outcomes, and Assessment Resource @ University of Pennsylvania
The Recruitment, Outcomes, and Assessment Resource (ROAR) was developed to meet several key research needs identified in the Cancer Center's strategic planning process; specifically, support in the design and implementation of non-therapeutic studies of cancer patients and individuals at increased risk (e.g., behavioral intervention trials) as well as observational studies of cancer patients and controls (e.g., genetic-epidemiology investigations).
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1 |
2012 — 2015 |
Kable, Joseph W (co-PI) [⬀] Lerman, Caryn |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Retraining Neurocognitive Mechanisms of Cancer Risk Behavior (Pq4) @ University of Pennsylvania
DESCRIPTION (provided by applicant): This study addresses the provocative question: Why don't more people alter behaviors known to increase cancer risk? (PQ4). Emerging work in behavioral economics has shed light on the critical role of reward-based decision-making processes in health risk behavior. In parallel, research in cognitive neuroscience has clarified the central role of the dorsolateral prefrontal cortices (DLPFC) in cognitive control during decision-making. Thus, we propose to integrate these lines of research and advance the science of behavior change by testing whether enhancement of DLPFC function via neurocognitive training improves decision-making processes that contribute to risk behavior. Young adults (ages 18-30; n=150) will participate in a five-week web-based neurocognitive training program or a cognitive stimulation (control) condition, based on random assignment. The evidence-based neurocognitive training focuses on enhancement of targeted cognitive processes to facilitate self-control and goal-directed behavior: sustained attention, working memory, and response inhibition. This intervention, shown to be highly effective for cognitive remediation in neuropsychiatric illness, has been adapted as a web-based tool for the proposed study to enhance cognitive function in healthy subjects. Importantly, our pilot data support the feasibility, high levels of compliance, and beneficial effects on neurocognitive performance. Our primary aim is to evaluate effects of neurocognitive training on neural activity and decision-making behavior. Our secondary aim is to examine the neurobehavioral mechanisms that mediate effects of neurocognitive training, including changes in executive cognitive function. Changes in decision-making processes and neural activity associated with neurocognitive training will be assessed at baseline and post-training by acquiring functional magnetic resonance imaging (fMRI) while participants perform reward-based decision-making tasks, specifically delay discounting and risk sensitivity. Cognitive performance will be assessed at these time points using a validated battery of tasks, in order to examine mediation effects. A three-month follow-up assessment will test the durability of the effects of neurocognitive training beyond the training period. Thus, this application breaks new scientific ground by applying novel concepts and tools from the field of cognitive neuroscience to accelerate the study of basic mechanisms of behavior change. These data will inform the development of novel and more comprehensive interventions for behavior change (e.g., combining neurocognitive training with existing behavioral interventions). As a basic mechanism study, the knowledge generated will be relevant to multiple health risk behaviors, enabling a potentially broad impact on cancer prevention.
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Dna Sequencing @ University of Pennsylvania
The DNA Sequencing Facility provides: reliable, long read, automated Sanger sequencing with fast turnaround; microsatellite-based genotyping and fragment analysis; plasmid and BAC DNA preparation and purification; and related molecular biological services including PCR, cloning, sub-cloning, site-directed mutagenesis, and preparation of targeting vectors for gene targeting in mice. It also provides services and support for analysis and interpretation of sequence data as well as the design of approaches to complex sequencing projects.
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Small Animal Imaging Core @ University of Pennsylvania
Animals; Cancer Center Support Grant; Image;
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Biostatistics Core Facility @ University of Pennsylvania
The Biostatistics Core provides support to ACC investigators through collaboration on the biostatistical design and analysis of research studies; preparation of statistical sections of clinical research protocols; review of clinical protocols on the CTSRMC; preparation of statistical sections of grant applications; and design of data management and research computing systems. The Core ensures that all clinical study protocols receive thorough scientific review regarding study design, analysis plans, and biostatistical justification. The Core regularly provides a variety of education activities, from formal courses to small group colloquia to impromptu one-on-one tutorials.
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Staff Investigators @ University of Pennsylvania
Cancer Center Support Grant; Research Personnel;
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Tobacco and Environmental Carcinogenesis Program @ University of Pennsylvania
The Tobacco and Environmental Carcinogenesis Program was established as a result of the ACC Strategic Planning Process undertaken in 2007. At that time the Cancer Epidemiology and Risk Reduction Program was reconfigured and renamed to reflect our trans-disciplinary research efforts to address health issues related to tobacco, asbestos, and polycyclic hydrocarbons as environmental carcinogens and in tobacco related risk reduction. With Caryn Lerman taking on the role as Deputy Director ofthe Cancer Center, new leadership was required. Dr. Lerman was replaced by Steven Albelda, M.D. and Trevor Penning, Ph.D. Dr. Albelda is a leading expert in mesothelioma and thoracic malignancies, and Dr. Penning is an internationally renowned expert on polycyclic aromatic hydrocarbon carcinogenesis. These leaders are experienced, well-funded investigators who are highly collaborative, as evidenced by their NIH P01, P50 and P30 grants. The TEC Program seeks to elucidate the relationships between cancer and exposure to known environmental carcinogens by studying the molecular mechanisms of carcinogenesis, developing and validating biomarkers of carcinogen exposure and response, determining genetic susceptibility to carcinogens, and improving strategies for the prevention, early detection and intervention of cancers with environmental causality. The initial focus of the program is on the etiology and prevention of tobacco- and asbestos-related cancers, particularly lung cancer, head and neck cancer, and mesothelioma. The cancer prevention focus includes studies on why people smoke, smoking cessation, and hence the prevention of the cancer initiation process. This research theme provides a solid foundation on which to build studies that relate exposures to environmental carcinogens to cancers in other organ systems. These collaborative research efforts are facilitated by the Program Leaders, multiple research retreats, monthly program meetings and seminars, and Pilot Project grants. Members of this program utilize multiple Shared Resources, with extensive use of the Biostatistics, Biomedical Data Coordination, Genomics, and Proteomics Cores. Further, members of this program were actively involved in the development of the new Recruitment Outcomes Assessment Resource (ROAR) Shared Facility, which has been highly valuable for ongoing case-control and gene-environment interaction studies. Future plans are to expand the TEC program to include other cancers with environmental causality, increase strength in environmental epidemiology and introduce new research themes in cancer chemoprevention and lung cancer stem cells. The 16 members in the TEC Program have $7,732,268 in research funding (Annual Direct Costs) of which $7,392,900 is peer-reviewed and $3,739,865 is NCI-funded. Among the many multi-investigator grants are the Center for Interdisciplinary Research on Nicotine Addiction (which has research themes in the molecular and behavioral mechanisms of smoking cessation) and the Center of Excellence in Environmental Toxicology (which has research themes in lung and airway disease, oxidative stress and gene-environment interactions). Members have published 317 cancer-related articles, with 30% being intra-programmatic and 26% being inter-programmatic.
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Biomedical Data Coordination Core @ University of Pennsylvania
The Biomedical Data Coordination Core (BDCC) provides service-oriented, applied database development, and data coordination that supports the expanded array of clinical and translational research projects/trials initiated by ACC Members. The BDCC will provide services for investigators along the full research continuum, including: 1) data resource needs assessment; 2) evaluation, selection, and deployment of commercial software tools; 3) development of specialized software systems; 4) support for data collection, management, and integration; 5) guidance on computing hardware support; and 6) education and training. The BDCC will also promote integrated transdisciplinary approaches to meeting data acquisition and storage needs of the ACC Members, leveraging a partnership with the Center for Translational Science Award (CTSA)-funded Center for Biomedical Informatics in Translation (BUT).
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Transgenic and Chimeric Mouse Facility @ University of Pennsylvania
Cancer Center Support Grant; Mus; Transgenic Organisms;
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Tumor Biology Program @ University of Pennsylvania
The Tumor Biology Program has witnessed growth in intra-programmatic and inter-programmatic efforts, both in terms of collaborative research and joint publications. Four thematic or affinity research groups have been spawned, unified by research meetings and symposia. Apart from consideration of other new thematic groups, the Program is working towards new interdisciplinary grants to the NIH and other sources.
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Tumor Virology Program @ University of Pennsylvania
The Program comprises a number of interactive and overlapping focus groups, which have continued to be productive, and form the basis for a high degree of interaction and collaboration. The Viral Oncogenesis focus group has a strong emphasis on the role of viruses as mediators of human cancers, including studies of Epstein-Barr virus (EBV), Kaposi's Sarcoma Herpesvirus (KSHV), human cytomegalovirus (HCMV), human papilloma virus (HPV) and hepatitis C virus (HCV), as well as other known tumor viruses: SV40 and Adenovirus. The DNA Virology focus group includes an excellent group of herpesvirus investigators who are studying herpes simplex viruses 1 and 2 and are focusing their work on viral infection and establishment of latency. The Retrovirology focus group studies HIV and AIDS-related malignancies as well as oncogenic murine retroviruses. The Viral Receptor focus group has strengths related to viral receptors and virus receptor interactions. The group includes members who have made major advances in understanding HIV receptors, avian leukosis virus (ALV) receptors and herpes simplex receptors. The General Virology focus group includes investigators studying Arbo-viruses, Corona-viruses and Bunya-viruses. Although not directly related to cancer, these investigators bring to the program expertise in RNA virology and classical virology, which have provided depth to the program and have proven vital for the general understanding of virus-host interactions. The general areas of viral-related research in the Tumor Virology Program include: 1) studies to determine the mechanisms mediating cellular transformation, immortalization and cell cycle dysregulation by viral encoded proteins; 2) studies to understand the role of viral proteins on cellular and viral gene expression and on control of cell metabolism, growth and survival; 3) research involving the structure and function of viral receptors and viral-receptor interactions; 4) investigation of the molecular biology and pathogenesis of retroviruses as they relate to AIDS and AIDS-associated malignancies; 5) studies focused on elucidation of the mechanisms of viral neuropathology; 6) studies to develop viral vectors for human gene therapy and cancer; and 7) development of vaccine strategies for the treatment of viral-associated cancers.
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1 |
2012 — 2014 |
Lerman, Caryn |
U01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
University of Pennsylvania (Upenn) Overall Coordinating & Clinical Trial Site @ University of Pennsylvania
Program Goals and Scope. Tobacco use is the foremost cause of premature death in the U.S. About 21% of adults are current smokers and smoking rates have not declined in recent years. Although available pharmacotherapies can aid in quitting smoking, quit rates vary substantially in subgroups of smokers. Thus, smoking is a significant clinical problem with a great need for research to improve treatment outcomes. The goal of the Pharmacogenetics of Nicotine Addiction Treatment (PNAT) research program is to generate the evidence base to optimize pharmacotherapeutic choices for individuals who wish to quit smoking. Building upon a strong foundation of translational pharmacogenefic (PGx) science conducted by this transdisciplinary team during the past 4 years. we propose in this competing renewal to: (a) conduct a multi-center prospective stratified PGx clinical trial to establish the predictive validity and cost-effectiveness of a genetically-informed biomarker to optimize smoking cessation treatment; (b) identify additional gene variants altering nicotine pharmacokinetics (PK), as well as pharmacodynamic (PD) gene variants influencing therapeutic response; and (c) elucidate causal mechanisms underlying associations of our PGx marker with smoking cessation.
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Cancer Therapeutics Program @ University of Pennsylvania
The Cancer Therapeutics Program membership includes clinical and basic science researchers whose shared focus is the translation of novel cancer therapies into new standards of care. This includes introduction of novel therapies developed in laboratories within the Abramson Cancer Center. In the period of the current report there has also been an initiative taken with one company (Pfizer) through which Penn investigators have obtained access to selected Pfizer compounds to pursue avenues of mutual interest that would not ordinarily rise to the priority within the company of receiving industry funding. Through this mechanism, the unexpected activity of an activating antibody directed to CD40 in pancreatic cancer has been discovered, as well as activity of a cdk 4/6-directed cell cycle inhibitor in two malignancies. The success of this collaboration is a constructive start to developing models for the optimal interaction of industry and academia in a time of intense scrutiny. For novel therapies that originate from industry sources in general, priority has been placed on the development of therapies for which Program members have scientific expertise regarding the pathways being perturbed or a research interest in defining responsive and refractory subpopulations.
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Human Immunology Core @ University of Pennsylvania
The mission of the Human Immunology Core (HIC) is to provide human immune assays and expertise to facilitate immunoassessment of clinical trials, and specimens and reagents to facilitate basic and translational research that enhances our understanding of the tumor microenvironment and the host immune response. During the previous five years the HIC has supported 25 early stage clinical trials. The HIC facility is directed by Cari June, Professor of Pathology and Laboratory Medicine. Dr. June is recognized for his contributions to basic human immunology and for leadership in translational and therapeutic human cancer immunotherapy. Dr. Jean Boyer serves as Technical Director of the facility. Dr. Boyer is an expert in the assessment of clinical cellular immune responses to vaccines and immunotherapy and oversees an experienced staff. Specifically the staff provides relevant immunologic assays and reagents for basic and clinical research. The HIC services include providing purified primary human blood cell subsets, and annotated specimen handling and storage. The range of services provided by the HIC staff also includes proliferation assays, multinational lymphocyte subset analysis by flow cytometry, as well as a number of assays to assess lymphocyte activation and specificity. Lymphocytes can be assessed by the quantitative and sensitive ELISpot assay, TCR repertoire, or by multiparameter techniques, intracellular cytokine staining and luminex bead array technology. Importantly, the staff works closely with each PI to be sure that the immunological assays are optimally matched to each clinical trial. The specific approach and assays that are applied to each clinical trial are discussed with the PI to most efficiently address the goals of the respective trial. The nature of the current immunological assays requires that an expert staff be available to perform assays and have knowledge of the instrumentation. Finally, the HIC can perform all studies on a pilot research basis, or at the standard of Good Laboratory Practices, as appropriate for the particular needs of the trial. By facilitating the immunoassessment of clinical cancer trials, the HIC supports clinical and translational scientists. By providing access to patient biopsy specimens, the HIC also facilitates research on the tumor microenvironment, thereby supporting the research of basic scientists as well. Over 40 ACC members have used the core in the last year. ACC member usage is 48% of the total core usage. CCSG support represents 21% of the proposed core budget with the remaining funding coming from charge backs and institutional support.
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Immunobiology Program @ University of Pennsylvania
In the last year, members of the Immunobiology Program have continued to make significant and sustained progress in its areas of focus: basic and tumor immunology, and translational medicine. The overall approach of program members combines molecular, cellular, structural, and biochemical strategies that are facilitated by the formal and informal intra- and interprogrammatic collaborations. Specifically, the Immunobiology Program aims to: 1. Understand the molecular and cellular regulation of the normal immune system and to define mechanistically the process by which malignant transformation occurs in cells of the immune system. 2. Utilize basic science discoveries of immune mechanisms to target malignant cells in relevant in vitro and animal model systems and in human clinical trials.
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Hematologic Malignancies Program @ University of Pennsylvania
The Hematologic Malignancies Program has two overarching scientific goals. These are to: 1. Employ state of the art technology to develop mechanisms based understanding of the cellular, biochemical, and molecular biology of normal and malignant hemato-lymphopoiesis. 2. Translate basic scientific discoveries into rational therapies that are more tumoricidal but at the same time, less toxic to normal tissues. To accomplish these goals, the investigators organize within thematic areas in both basic and clinical science. All areas focus on translation as a goal of the wori< conducted. Basic scientists focus on transcription, signal transduction, and animal modeling of disease pathogenesis and treatment. Clinical scientists self-align with one of 4 affinity groups: Leukemia/MDS/MPN, Lymphoma, Myeloma/Autologous Stem Cell Transplantation, or Allogeneic Stem Cell Transplantation. Individual investigators, basic or clinical, function autonomously, but the structure of this ACC program promotes collaboration with shared data, ideas, and when appropriate to implement initial translational studies. Promising approaches are brought quickly to clinical trials (see Figure 1).
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Cancer Control Program @ University of Pennsylvania
The overarching goal of the CCP is to reduce cancer incidence and improve cancer outcomes by generating new knowledge about the genetic, behavioral and health care determinants of cancer risk and outcomes and the effectiveness of strategies for reducing risk and improving outcomes. Because the breadth of research encompassed under this goal is large, CCP leadership has identified several key areas for scientific emphasis based upon the ACC strategic plan, scientific opportunities, and program member interests and strengths. These areas have remained stable over the last several years; however, these priorities will be reexamined with the recruitment of new program leadership and through the new strategic vision for the ACC with the recruitment of Dr. Dang as the ACC Director. These areas of emphasis are organized as research themes and include:Communication and behavior change, Disparities, Genetics, Health care outcomes.
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Melanoma and Cutaneous Malignancies Program @ University of Pennsylvania
The Melanoma and Cutaneous Malignancies Program represents an expansion of the former Melanoma Program which has been continuously funded by the CCSG since 1978. Dr. Lynn Schuchter has led the program since 2007, having been an active member since 1989. The overall goals of the Melanoma and Cutaneous Oncology Program are: 1. To understand the genetics, epidemiology, molecular mechanisms, and biology of cutaneous malignancies; 2. To translate approaches from the preclinical arena into novel treatment strategies; and 3. To foster and support intra and interprogrammatic and external scientific collaborations to better understand the biology and therapy of cutaneous malignancies The research interests and efforts of program members are centered on four highly translational themes. 1. Epidemiology and Risk Assessment 2. Genomics 3. The Biology of Cutaneous Malignancies 4. Experimental Therapeutics
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Genomics Facility @ University of Pennsylvania
Cancer Center Support Grant; Genomics;
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Clinical Research Unit @ University of Pennsylvania
The Clinical Research Unit (CRU) is critical to the conduct of clinical research at the Abramson Cancer Center (ACC). This core is a centralized administrative unit that coordinates protocol management, budget and financial analysis, regulatory affairs expertise, research nursing support, and data management for therapeutic clinical trials conducted by ACC investigators. The CRU supports peer-reviewed funded clinical research projects, invesfigator-initiated clinical trials, cooperative group trials, and industry-sponsored trials. All trials supported by the CRU are approved by the ACC Clinical Trials Scientific Review and Monitoring Committee and are subject to ACC Data and Safety Monitoring Committee internal audits. By providing the necessary infrastructure for the transfer of preclinical discoveries into the clinic, this core is central to the ACC mission to support translational research and high impact clinical trials. The availability of a senior scientific leader, who is an expert in clinical trials management, as well as highly skilled research personnel, allows ACC clinical invesfigators to develop and conduct a comprehensive range of clinical trials for all types of cancer that involve both novel agents and innovative treatment approaches. In response to the 2004 CCSG critique ofthe CRU, the ACC has implemented Velos eResearch, a clinical trials management system. This information system will improve efficiency of CRU operations and ensure data standardization and regulatory compliance. Additional changes in the clinical research infrastructure have enhanced the function of this core. These include the establishment of disease-specific research groups charged with the responsibility of managing their portfolio of clinical trials, based upon scienfific goals and available resources; the establishment ofthe Strategic Planning and Resource Committee, a centralized group that reviews a proposed protocol to be certain that adequate resources are available to support the trial and that the budget is appropriate. These additional reviews help assure that the resources ofthe CRU are focused on the highest priority clinical trials conducted by ACC members. From 1/2009 to 12/2009 49 new therapeutic clinical trials have been activated by the CRU. CCSG support represents 20% ofthe core's proposed budget with the remaining funding coming from other grants/contracts and institutional support.
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Clinical Imaging Core @ University of Pennsylvania
The Clinical Imaging Core (CIC) provides comprehensive radiologic expertise to support the use of routine and novel imaging methodologies for translational cancer research. The CIC utilizes the full complement of medical imaging resources at the University of Pennsylvania, including PET/SPECT, MRl, CT, ultrasound, mammography/tomosynthesis, and near infrared optical imaging. The CIC is also complemented by a large research infrastructure in radiology and biomedical engineering at the University of Pennsylvania, providing access to computational resources, advanced imaging display, and processing in the 3D Radiology Core laboratory. The CIC will also support a cadre of clinical coordinators with special expertise in the management of patients and imaging in the course of clinical trials, offering logistical and regulatory support in pursuit of clinical imaging research in oncology.
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Flow Cytometry and Cell Sorting Facility @ University of Pennsylvania
The Flow Cytometry and Cell Sorting Facility continues to see steady use, with a significant increase in annual usage since the last site visit in 2010. 120 members of the Abramson Cancer Center used the facility in the past year
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Developmental Funds @ University of Pennsylvania
Eight investigators were awarded Core Grant Developmental Funds through the Cancer Center's internally peer-reviewed Pilot Projects Program. This program offers seed money grants to investigators with innovative cancer research projects that have not yet received peer-reviewed funding. Awards are determined based on several criteria, including the overall scientific merit and innovativeness of the proposed project and the track record or ability of the applicant to become a highly regarded, externally funded cancer investigator. Pilot project awards are also made within the context of the strategic priorities of the ACC.
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Clinical Cell and Vaccine Production Facility @ University of Pennsylvania
The CVPF continues to enable the bench to bed translation of early phase cellular therapy trials for cancer researchers at the ACC, and is currently supporting clinical manufacturing for 13 cancer trials to treat patients with hematologic malignancies and solid tumor cancers.
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1 |
2012 — 2015 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Pediatric Oncology Program @ University of Pennsylvania
The Program is designed to promote this translational research mission by fostering integration and identifying key gaps. The membership has grown strategically to cover the majority of major themes in the field of pediatric oncology, and we currently have focused research efforts in: 1) Genetics, Genomics and Epidemiology; 2) Biology and Signal Transduction; 3) Immunobiology and Transplantation, 4) Drug Development, Clinical Pharmacology and Clinical Research; and 5) Survivorship, Psychology and Outcomes.
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1 |
2013 — 2015 |
Hornik, Robert C. [⬀] Lerman, Caryn (co-PI) |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Core C: Tobacco Factcheck (Tfc) Core P263-279 @ University of Pennsylvania
Advertising; Air; Cigarette; Communication; Complex; Diffuse; Environment; experience; Feminine; high school; Individual; Journals; Masculine; Names; news; programs; Public Policy; Site; Smoke; Smoking; Source; Speech; Students; Tobacco; Visual; web site;
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1 |
2013 — 2017 |
Hornik, Robert C. [⬀] Lerman, Caryn (co-PI) |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Developmental/Pilot Project Program P280-287 @ University of Pennsylvania
Program Director/Principal Investigator (Last, First, Middle): Hornik, Robert & Lerman, Caryn - Developmental/Pilot Project Program DEVELOPMENTAL/PILOT PROJECT PROGRAM DESCRIPTION A. OVERVIEW AND AIMS The University of Pennsylvania (UPENN) TCORS Developmental/Pilot Project will stimulate and promote high- priority innovative projects responding to emerging scientific questions from the Penn TCORS and enable a rapid response to new developments in the scientific and regulatory communities at large. This program follows the successful operating model of the pilot research programs in the NCI Penn Center of Excellence in Communication Research (CECCR) and Center for Interdisciplinary Research on Nicotine Addiction (CIRNA). This established infrastructure includes mechanisms to: solicit pilot projects; review and support pilot projects; evaluate the success of funded projects and the program overall; and foster the development of new grant applications for the most promising pilot projects. The developmental projects also provide opportunities to involve researchers with varied disciplinary backgrounds, apply new research technologies, and foster new collaborations in the area of tobacco research of relevance to the FDA. Although we anticipate that most within-Center pilot projects would relate to the Center's theme of
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1 |
2013 — 2017 |
Hornik, Robert C. [⬀] Lerman, Caryn (co-PI) |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Upenn Tcors: Tobacco Product Messaging in a Complex Communication Environment @ University of Pennsylvania
DESCRIPTION (provided by applicant): Public communication about tobacco products has been transformed by the digital marketing revolution and the rapid diffusion of emerging social media. As a result, tobacco product information and misinformation is readily accessible through a variety of sources: from mass media sources (e.g., newspapers, TV), to social media (e.g. Twitter) and user commentary on media, to the final communication vehicle, the cigarette package itself. Such misinformation can mislead the public to underestimate the dangers or overestimate the benefits of various tobacco products, and threatens to undermine FDA's regulatory efforts. The U Penn TCORS responds to these challenges with a thematic focus on tobacco-related messaging in a complex public communication environment. Specifically, our Center will: (a) characterize the public communication environment to understand how it affects what people know about tobacco products, what they believe about these products, and their use of these products, and (b) determine the most effective strategies for the FDA to convey information and correct misinformation about tobacco products and use. Addressing this problem at a macro level, Project 1 examines information and misinformation about tobacco products in traditional and emerging media and how exposure to this information alters beliefs, attitudes, intentions, and tobacco use. Project 2 examines the staying power of beliefs about tobacco products and tobacco use that are based on misinformation in electronic social media and evaluates corrective interventions. Both Projects 1 and 2 focus on youth and young adults, whose perceptions and behavior may be most affected by internet-based information. Project 3 provides a detailed analysis of the effects of a particular form of implicit misinformation on tobacco use behavior - the use of color packaging by the tobacco industry to mislead the public to underestimate product harm. Two novel cross-cutting research cores will serve these projects: a Media Data Acquisition and Content Analysis Core that will acquire, code, and manage tobacco product information available in emerging media sources, and a Tobacco FactCheck Core that will develop and deploy novel tools to evaluate this information for false and deceptive claims about tobacco products and disseminate corrective information. Our Developmental Pilot Program will enable us to respond to emerging scientific opportunities and support new collaborative research activities, and our Training Program will develop the next generation of tobacco control regulatory scientists with a focus on communication research. An Administrative Core coordinates all of these activities utilizing proven strategies for facilitatin interdisciplinary coordination and communication in P50 Centers. RELEVANCE: The UPENN Tobacco Center of Regulatory Science (TCORS) will generate novel data to guide the FDA's efforts to convey information about tobacco products and to correct misinformation disseminated through public communication sources. Our Center will also develop and deploy novel methodologies and tools for the acquisition and analysis of tobacco product information in public media for use by the FDA, other agencies, and the scientific community.
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1 |
2013 — 2017 |
Hornik, Robert C. [⬀] Lerman, Caryn (co-PI) |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Core a: Administrative Core P226-246 @ University of Pennsylvania
Address; authority; Collaborations; Communication; Complex; Development; Digital Libraries; Educational workshop; Electronics; Ensure; Environment; Expenditure; experience; Fostering; Goals; innovation; Interdisciplinary Study; Manuscripts; Measures; meetings; Monitor; Newsletter; Pilot Projects; Policy Maker; Policy Research; Press Releases; Process; Productivity; programs; Progress Reports; Protocols documentation; Reporting; Research; Research Personnel; Research Project Grants; response; Science; Scientist; Series; sharing data; Strategic Planning; success; System; TNFRSF5 gene; Tobacco; United States National Institutes of Health; web site; Work; working group;
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1 |
2013 — 2017 |
Hornik, Robert C. [⬀] Lerman, Caryn (co-PI) |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Tcors Training and Career Development Program P288-301 @ University of Pennsylvania
Program Director/Principal Investigator (Last, First, Middle): Hornik, Robert & Lerman, Caryn - Training and Career Development Core A.
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1 |
2013 — 2017 |
Hornik, Robert C. [⬀] Lerman, Caryn (co-PI) |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Core B: Media Data Acquisition and Content Analysis Core (Mdaca) Core P247-262 @ University of Pennsylvania
Adult; American; Communication; Complex; data acquisition; Diffusion; Environment; Internet; Low income; Personal Communication; Population; Reporting; social; social networking website; Tobacco; young adult;
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1 |
2013 — 2017 |
Hornik, Robert C. [⬀] Lerman, Caryn |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Project 3: Effects of Implicit Messaging by Cigarette Pack Color On Smo P196-225 @ University of Pennsylvania |
1 |
2013 — 2017 |
Hornik, Robert C. [⬀] Lerman, Caryn (co-PI) |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Project 2: Belief Echoes: Intervenfions to Correct Misleading Informaf P160-195 @ University of Pennsylvania
Belief; Cigarette; Communication; Complex; Environment; Marketing; Misinformation; Nicotine; Tobacco;
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1 |
2013 — 2017 |
Hornik, Robert C. [⬀] Lerman, Caryn (co-PI) |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Project 1: Information and Misleading Information About Tobacco Product P125-159 @ University of Pennsylvania |
1 |
2015 — 2021 |
Lerman, Caryn E. |
R35Activity Code Description: To provide long term support to an experienced investigator with an outstanding record of research productivity. This support is intended to encourage investigators to embark on long-term projects of unusual potential. |
Neuroscience-Based Interventions For Cancer Risk Behavior Change @ University of Pennsylvania
? DESCRIPTION (provided by applicant): Tobacco use and obesity account for over 45% of preventable cancer deaths. Yet, these cancer risk behaviors are resistant to long-term change, despite widespread knowledge of the risks. Even with the best treatments available, most people revert to their former practices of cigarette smoking or eating. While behavior change interventions may address the habitual nature of these behaviors, they do not tackle the disruptive brain processes that undermine sustainable behavior change. Tobacco use and obesity are associated with cognitive impairments and altered brain functions that can interfere with the maintenance of goal-directed behaviors. More specifically, work in my laboratory points to the central role of alterations in working memory-related activation in the dorsolateral prefrontal cortices (DLPFC). DLPFC is at the core of the brain's cognitive control network, which supports planning, decision- making, and cognitive (self) control. Importantly, our pilot data show that DLPFC function can be safely restored using a novel and low-cost neuroscience-based intervention. Thus, the bold premise of this application is that it is possible to enhance th brain's capacity to over-ride behavioral habits that contribute to obesity and cigarette smoking, and ultimately to cancer. Broad Plan: Extending our pilot work, the proposed 7-year research plan begins with a Proof of Mechanism experiment to validate the effects of DLPFC-targeted transcranial direct current brain stimulation (tDCS) with cognitive training. Progressing to the Proof of Principle stage, experiments will identify the optimal type of cognitive training to complement tDCS and the optimal number of treatment sessions, with a focus on intermediate endpoints (e.g., cognitive function, risky decision-making, self-reported behaviors). In the final stage of the research plan, Phase II randomized controlled clinical trials will evaluate the efficacy of the optimized neuroscience-based interventions for individuals seeking treatment for smoking cessation (Study 1) and weight loss (Study 2). The deliverables are efficacious neuroscience-based interventions to be validated in Phase III clinical trials and translated to practice for behavioral cancer prevention. Qualifications: As the Mary W. Calkins Professor of Psychiatry and Deputy Director of the Abramson Cancer Center at UPenn, I have decades of experience conducting innovative behavioral science research that bridges the fields of neuroscience, pharmacology, and genetics. I have been continuously funded by NCI since 1989, with grants totaling ~$67 million in total costs (including an NCI Provocative Question Award). With >345 peer-reviewed publications, my Google Scholar H-INDEX is 90. My service includes membership on the NCI Board of Scientific Advisors, National Human Genome Research Advisory Council, and the National Institutes on Drug Abuse Advisory Council. I am a past President of the Society for Research on Nicotine and Tobacco, and an Elected Member of the Institute of Medicine of the National Academies.
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1 |
2016 — 2019 |
Lerman, Caryn E. Loughead, James W (co-PI) [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Neural Basis of Smoking Relapse @ University of Pennsylvania
? DESCRIPTION (provided by applicant): Smoking is the greatest preventable cause of mortality and a significant economic burden. Even with the best available treatments, most smokers relapse within days or weeks after a quit attempt. To improve quit rates significantly, we need a more refined mechanistic understanding of why so many smokers who attempt to quit will relapse quickly. The proposed functional magnetic resonance imaging (fMRI) study integrates concepts and tools from the fields of cognitive neuroscience and behavioral science to determine how brain states in early abstinence influence clinical outcomes among treatment-seeking smokers. The primary aims of this hypothesis-driven study are: (1) to identify brain mechanisms that increase vulnerability to smoking relapse, and (2) to test an integrated brain-behavior model of smoking relapse. Using our validated fMRI-based abstinence challenge paradigm, 200 treatment-seeking smokers will complete two 1-hour pre- treatment fMRI scans: after smoking satiety and after 24 hours of confirmed abstinence. We will examine neural and behavioral responses during performance of validated tasks probing working memory, cue reactivity, and stress response as well as resting state functional connectivity. Participants will then set a target quit date, receive smoking cessation counseling, and be monitored for 6-months to assess time (days) to relapse, using a validated smoking relapse protocol. The primary outcome is time to relapse. Secondary outcomes include abstinence symptoms and smoking status at 30 days. For human subjects reasons, relapsing smokers will be offered an opportunity to receive 8 weeks of nicotine patch treatment and counseling free of charge following study completion. Although neuroimaging is not likely to become a standard pre- cessation assessment the near future, this study will elucidate pathological neurobehavioral processes and specific neurocognitive domains that can be targeted in new treatments to aid smoking cessation.
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1 |
2019 — 2021 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Pilot Research Project Core @ University of Pennsylvania
PILOT PROJECT CORE As the ?implementation? arm of the PACE, the Pilot Project Core will drive novel discoveries in OUD that are uniquely enabled by PET imaging. Pilot projects will leverage the Radiochemistry Core, Imaging Core, and Clinical Core, and the Administrative Core will support training and career development. The Specific Aims are: (1) to accelerate the science of OUD through a set of inter-related and rigorous pilot projects that leverage the PACE infrastructure. An initial set of vetted pilot projects will elucidate the role of mu- and delta- opioid receptor availability in OUD and its treatment, the influence of genetic variation on receptor availability and therapeutic dosing in OUD, (c) the role of the kappa-opioid receptor in suicidal ideation in OUD, and the mechanistic role of neuroinflammation in OUD with or without HIV; (2) to oversee a fair and transparent process to solicit, review, support, and evaluate innovative and rigorous future pilot projects. Working with the Administrative Core, the Pilot Core will solicit applications on an annual basis beginning in year 2 through direct outreach to Departments and Centers at Penn and Yale, and through campus-wide emails; conduct a scientifically rigorous internal NIH-style review process with transparent merit criteria, provide interdisciplinary mentoring and support, including scientific planning and methodological and technical assistance, and evaluate the success of these efforts; and (3) to train the next generation of addiction PET imaging scientists. These activities include didactic and experiential training in PET imaging, data analysis, and OUD neurobiology, and interdisciplinary co-mentorship and career development opportunities. Training initiatives will attract and support both early-stage investigators and established investigators who wish to incorporate PET imaging into addiction research. Finally, an annual PACE Research Day will convene Penn's active PET researchers, the PACE's Internal and External Advisory Boards, and new investigators to share the latest research findings and to encourage collaborations with the new P30 PET tools.
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1 |
2019 — 2020 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Usc Norris Comprehensive Cancer Center (Core) Grant @ University of Southern California
? DESCRIPTION (provided by applicant): The Molecular Genetics Program has been continuously approved through the NCI CCSG since the USC Norris first received NCI designation over 35 years ago. This Program has always been distinguished nationally for its strength in DNA replication and DNA repair, with an emphasis on applying discoveries toward cancer chemotherapy. During the project period, Preet Chaudhary joined Michael Lieber as Co-Leader to add depth in translation and oversee a new theme on the molecular genetics of cancers associated with infection by HHV8, including the development of targeted therapies for the treatment of these cancers. The Program has three integrated aims: 1) DNA replication, cell cycle, and cell proliferation in genetic instability; 2) DNA repair and recombination in genetic instability; and 3) viral oncogenesis with an emphasis on HHV8. Lymphoid malignancies are used as a disease model used by Program members for all three aims. Members continue to be highly interactive within and across themes and across program boundaries. The 39 Program members, who come from three schools and 13 departments, have $11.4M in peer-reviewed funding (direct costs), of which 18% is from NCI, 61% from other NIH sources, and 8% from other peer-reviewed funding sources. The Program is highly productive with 439 publications of which 21% are inter-programmatic, 15% intra-programmatic and 25% inter-institutional. Program Leaders organize retreats and mini-symposia several times per year to cross-fertilize research within and across Programs while remaining watchful to ensure a high level of member crosstalk. This has led to high success in securing new P01s that are intra- and inter-programmatic, while also cross-cutting thematically. Examples include renewal of an NCI P01 on understanding human DNA polymerase active sites and development of new chemotherapeutics (Goodman, McKenna, Warshel), and a new NCI P01 on viral oncogenesis by KSHV (HHV8) (Jung, Feng, Gao). Members have been particularly successful in seeking new cancer drug therapies, which has been achieved with the Translational and Clinical Sciences Program.
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0.951 |
2020 |
Lerman, Caryn |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Administration (Admin Core) @ University of Southern California
Project Summary/Abstract Administration is responsible for providing expert administrative support to Cancer Center leadership and services to members in order to foster highly interactive scientific environment that encourages interdisciplinary cancer research across programs, departments and the cancer continuum, and fosters new interactions, collaborations, and engagement. Led by the Associate Director for Administration and Education, the administrative team has been instrumental in developing new Research Programs and Shared Resources; coordinating and managing planning and evaluation activities to assure continued excellence in meeting USC Norris and member needs; advocating, prioritizing and managing resources for the benefit of USC Norris and its members; and ensuring that our researchers have the infrastructure, systems, and assistance needed to conduct important research in an interdisciplinary collaborative manner. Senior Leadership is comprised of the Director and five Associate Directors (basic research, adult oncology, cancer prevention and control, pediatric oncology, and administration and education). Senior Leaders set the strategic research directions of USC Norris through an integrated strategic planning, evaluation and process improvement approach. This highly effective process includes Program Leaders, members, Shared Resource Directors, and the External Advisory Board. This complements the role of Associate Directors who share direct responsibility for scientific oversight of Research Programs and Shared Resources. The shared oversight model encourages a high degree of interaction and joint development of interdisciplinary and collaborative research. As an example, the Senior Leaders worked together to define and clarify the goals for the new Program in Translational and Clinical Sciences. Together, they also ensure that the educational and training activities of the Center are appropriate and aligned with our scientific goals and that the cancer problems of the catchment area are addressed through both programmatic research and outreach activities. Oversight of clinical protocol development and resources to support innovative clinical research is provided by the Associate Director for Adult Oncology. The Associate Director for Pediatric Oncology helps assure the integration of pediatric populations and facilitates translation of research from basic science laboratories. The Associate Director for Administration and Education provides strategic oversight of the business and financial operations of USC Norris. Her administrative team provides the administrative, fiscal, information technology, facilities management, communication, and planning support required to effectively and efficiently enable Senior Leaders to realize the vision of USC Norris and meet the needs of investigators conducting leading- edge cancer research.
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0.951 |