Eleftheria Maratos-Flier - US grants
Affiliations: | Harvard Medical School, Boston, MA, United States |
Area:
Hypothalamic regulation of central and systemic function related to energy balanceWe are testing a new system for linking grants to scientists.
The funding information displayed below comes from the NIH Research Portfolio Online Reporting Tools and the NSF Award Database.The grant data on this page is limited to grants awarded in the United States and is thus partial. It can nonetheless be used to understand how funding patterns influence mentorship networks and vice-versa, which has deep implications on how research is done.
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High-probability grants
According to our matching algorithm, Eleftheria Maratos-Flier is the likely recipient of the following grants.| Years | Recipients | Code | Title / Keywords | Matching score |
|---|---|---|---|---|
| 1985 — 1988 | Maratos-Flier, Eleftheria | K08Activity Code Description: To provide the opportunity for promising medical scientists with demonstrated aptitude to develop into independent investigators, or for faculty members to pursue research aspects of categorical areas applicable to the awarding unit, and aid in filling the academic faculty gap in these shortage areas within health profession's institutions of the country. |
Viral Pathogenesis in Endocrine Cells @ Joslin Diabetes Center My primary research interest is the mechanisms by which viruses interact with endocrine cells. My long-term goal is to continue to do research in an academic setting. Diabetes mellitus is a serious illness which produces significant morbidity and mortality in man. To date, no clear etiology has been defined, although autoimmunity plays a role in Type I diabetes. Viruses have also been suggested as etiologic agents, however, interactions between viruses and endocrine cells are poorly understood. We have examined several aspects of the interaction of reovirus with endocrine cells. The effects of viral infection on endocrine cells has been studied. We have also evaluated receptors for viruses on endocrine cells, processing of virus by endocrine cells, and the effect of lysosomotropic agents on viral growth. Finally, we have generated persistently infected cells and shown that these cells demonstrate structural and functional alterations. The experiments represent a continuation of these initial experiments. We hope to further characterize receptors for type 1 and type 3 reovirus. Utilizing our system of in vivo clearance we will evaluate potential regulators of clearance. We will extend our understanding of processing of virus by endocrine cells, by probing processing using lysosomotropic agents. Finally, we propose to persistently infect endocrine cells in order to study the effects of viral persistence on hormone synthesis and secretion. |
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| 1990 — 1994 | Maratos-Flier, Eleftheria | 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. |
Molecular Characterization of the Reovirus Receptor @ Joslin Diabetes Center Reoviridae; virus receptors; protein structure; virus genetics; Reoviridae disease; protein biosynthesis; synthetic peptide; nucleic acid sequence; complementary DNA; ligands; cell differentiation; molecular pathology; molecular genetics; genetic regulatory element; receptor expression; receptor binding; membrane proteins; affinity chromatography; mutant; nucleic acid probes; site directed mutagenesis; laboratory rat; western blottings; transposon /insertion element; |
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| 1998 — 2002 | Maratos-Flier, Eleftheria | 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. |
Anatomic and Physiologic Characterization of McH Action @ Joslin Diabetes Center DESCRIPTION (Adapted from the applicant's abstract): Obesity is a serious illness with a complex etiology and a major risk factor for type II diabetes. Although obesity is common, the causes of obesity are poorly understood. A number of peripheral hormones and central neuropeptides have been implicated in the pathogenesis of obesity. Using PCR-differential display, we recently discovered that the mRNA in the neuropeptide melanin- concentrating hormone (MCH) is increased in the hypothalamus of ob/ob mice. In addition, MCH mRNA levels are regulated by fasting. To confirm that MCH is also increased and functions as an orexigenic factor, rats were injected with MCH-treated analogs through cannulas placed in the lateral ventricle in both normal and ob/ob animals. MCH induces an acute and profound increase in chow consumption. MCH also interacts with the melanocortin system. In fish, MCH induces melanosome aggregation while MSH induces dispersion. In mammals, the two peptides are antagonistic on a number of behaviors, and we have found that MCH and MSH act as mutual antagonists in a feeding paradigm. Unlike agouti, another inhibitor of MSH, MCH does not act on any of the known melanocortin receptors. MCH neurons, which are localized to the lateral hypothalamus project diffusely throughout the brain. Little is known about which specific areas of the brain parenchyma may be important in mediation MCH action. Virtually nothing is known about the MCH receptor, or about MCH-mediated signal transduction. Our preliminary data in scales from the common carp indicate that MCH does not act through cAMP or cGMP, but that it stimulates PI 3- kinase activity. The investigators propose to analyze the neuroanatomical basis of MCH action by performing functional and mapping studies, and we will couple these studies with analysis aimed at understanding the mechanism of its physiological action. Finally, we will analyze the effect of MCH gene ablation in a MCH knockout mouse. |
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| 1999 — 2002 | Maratos-Flier, Eleftheria | P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
McH Action as Defined Through Gene Knockout @ Beth Israel Deaconess Medical Center Obesity is a serious medical condition with complex etiology; it is a significant risk factor for a number of illnesses including type II diabetes, coronary artery disease a number of neoplasms including endometrial and colon cancer. Although very common, the causes of obesity are poorly understood and available treatments are not particularly effective. A number of peripheral hormones and neuropeptides have been implicated in the pathogenesis of the impaired energy balance which results in obesity. We discovered that the hypothalamic peptide, melanin concentrating hormone is important in the regulation of energy balance. In addition to a number of physiologic studies we generated a mouse in which the MCH gene was ablated. Homozygous MCH-/- mice have a lean phenotype, with a 25% reduction in total body weight and 50% reduction in total body fat and reduced levels of leptin. Decreased eating during the dark cycle contributes t least in part to the phenotype, however, the reduction in eating is only 15%. Preliminary data indicates that ablation of the MCH gene may also lead to increased oxygen consumption. This study proposes to examine the causes of the lean phenotype in detail and to ascertain the relative contributions of MCH and the two other peptides derived from the MCH gene, N-EI and N- GE. To determine the role of MCH in mediating the orexigenic or appetite inhibiting actions of other neuropeptides (NPY, alphaMSH, GLP-1) the effect of a number of appetite regulating peptides in MCH-/- mice will be assessed. In addition to examine the importance of MCH in mediating obesity in single gene models of rodent obesity MCH-/- mice will be crossbred to leptin deficient (ob/ob) mice and leptin resistance A/gamma (agouti) mice. MCH-/- mice will also be crossbred to mice with ablations in NPY or orexin, other neuropeptides implicated in energy, balance, to determine the effect of multiple gene ablation on energy balance. |
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| 1999 — 2003 | Maratos-Flier, Eleftheria | 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. |
Gene Targeting Approaches to McH and Energy Balance @ Joslin Diabetes Center DESCRIPTION: (Adapted from the applicant's abstract) This study proposes to characterize the lean phenotype in MCH knockout mice, and to ascertain the relative contributions of MCH and the two other peptides derived from the MCH gene, N-EI and N-GE. To determine the role of MCH in mediating the orexigenic or appetite inhibiting action of other neuropeptides the effect of appetite regulating peptides in MCH-/-will be assessed. In addition to examining the importance of mediating obesity in single gene models of rodent obesity, MCH-/-mice will be crossbred to leptin deficient (ob/ob) mice and leptin resistant A (agouti) mice. MCH-/- mice will be crossbred to mice with ablations NPY or orexin, other neuropeptides implicated in energy balance. Finally to determine the importance of MCH in mediating obesity in response to environmental agents, the ability of a high fat diet, MSG and GTG to cause obesity will be compared in wild type and MCH-/- animals. |
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| 2001 | Maratos-Flier, Eleftheria | 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. |
Defining the Molecular Components of Glut4 Translocation @ Joslin Diabetes Center In adipose tissue and skeletal muscle insulin induces the translocation o f GLUT4-containing vesicles to the ell surface resulting in an increase in glucose uptake. The mechanism of GLUT4 translocation is poorly understood. Recently several proteins involved in regulated exocytosis in neural and neuroendocrine tissues have been shown to be expressed in insulin-sensitive tissues. These proteins are components of the SNARE complex. In addition, members of the RAB family of small GTP-binding proteins that are involved in regulated endocytosis/exocytosis are also present in adipocytes and skeletal muscle. While these proteins have been implicated in insulin-regulated GLUT4 translocation no functional role has been determined. However, we have recently established that SNARE- complex proteins and specific members of the Rab family are necessary components in the GLUT4 translocation machinery. We have also identified a potentially novel protein that interacts with Rabs in adipocytes in an insulin-regulated manner. It is the purpose of this proposal to extend our preliminary observations to include a more detailed biochemical and cell biological analysis of these molecules. These studies will include experiments designed to investigate the specificity of protein-protein interactions between the SNARE proteins and their regulation by insulin, identification of other novel Rab-interacting proteins and pursuit of their molecular cloning. Data from these studies will allow us to define a more contemporary model of insulin-regulated glucose uptake. |
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| 2002 | Maratos-Flier, Eleftheria | G20Activity Code Description: To provide funds for major repair, renovation, and modernization of existing research facilities. These facilities may be the clinical research facilities, animal research facilities, and other related research facilities. |
Development of a Mouse Monitoring System @ Joslin Diabetes Center DESCRIPTION (Provided by applicant): The use of genetically altered mice has become a standard biological technique aimed at addressing both the physiologic role and molecular mechanism of action of various peptides. Typically studies of transgenic or knockout mice involve specific studies of the peptide of interest. However, it is increasingly apparent that alterations of peptide expression through transgenic or knockout animals may have unexpected effects. In the case of obesity and Type II diabetes, alterations in molecules regulating body weight and glucose homeostasis may lead to changes in overall energy homeostasis that may result from changes in feeding, changes in energy expenditure or altered hormone sensitivity. These results may be expected or unpredictable, as the targeted peptide may be involved in unknown interactions with other molecules. Hence, in evaluating transgenic or knockout models it is essential that in addition to examining parameters such as body weight and insulin sensitivity it is important to examine energy expenditure and oxygen consumption through calorimetry as well as to properly evaluate patterns of feeding behavior. There are nine investigators involved in research on obesity and diabetes who are actively using close to 50 different genetically engineered mouse models. Many of these models have an obese or lean phenotype, which must involve either changes in feeding or energy expenditure or both. This applications for the CLAMS, if funded, will allow analysis of energy expenditure in these animals and general behavior as well as allow precise monitoring of feeding and drinking. This analysis is essential for understanding the perturbations that lead to obesity and diabetes. Use of this instrument will be integrated with the Animal Core funded by the JDC National Institutes of Health (NIH)-funded Diabetes and Endocrinology Research Center (DERC) (DK 36836) which will be increasingly focused on physiologic and behavioral evaluation of mice. |
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| 2005 — 2009 | Maratos-Flier, Eleftheria | P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
@ Beth Israel Deaconess Medical Center Evaluation of energy expenditure has become an indispensable tool for studies involving lean and obese mice. Systems capable of such evaluation are commercially available and can monitor activity, oxygen consumption, CO2 production, feeding and drinking. From this data respiratory quotient, RER and heat produced can be calculated. However the systems are expensive and sophisticated. The Endocrine Division at BIDMC has a sixteen animal monitoring system purchased by outside funds. To make the technology available to PPG investigators, monitoring is offered as a core service. Following monitoring data is provided to the requesting investigator as Excel spreadsheets and graphs plotting the variable of interest in real time. The core assists in experimental design and data analysis. An additional service of the core is assistance with DEXA monitoring for PPG projects. |
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| 2005 — 2009 | Maratos-Flier, Eleftheria | P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
McH and the Integration of Energy Balance @ Beth Israel Deaconess Medical Center Obesity has become a serious health problem in the United States. Once obesity is established there is little effective treatment. It is increasingly apparent that in addition to excess food intake, energy expenditure is an important contributor to the development of obesity, both in rodents and humans. Energy expenditure has several components including resting energy expenditure and the energy spent during locomotor activity (motivated behavior). It is now recognized that peptides that play are role in feeding also regulate energy expenditure. Thus peptides that increase appetite then to decrease energy expenditure while those that inhibit appetite tend to increase energy expenditure. Melanin-concentrating hormone (MCH) was initially identified as a neuropeptide that stimulates appetite. It has also emerged as a key regulator of energy expenditure and has effects both on resting energy expenditure, probably through modulation of sympathetic activity, as well as energy expenditure associated with locomotor activity, most likely through influences on dopaminergic signaling. We have developed a mouse model lacking the gene for MCH (MCH-KO or MCH-/-) and backcrossed the animals for 10 generations onto a homogeneous genetic background, C57BL/6. Mice lacking MCH are lean. On a mixed background leanness resulted from a combination of decreased feeding and increased energy expenditure. On the BL/6 background the lean phenotype is secondary to increased energy expenditure. On a chow diet, resting energy expenditure is increased and there is no change in locomotor activity. Mice lacking MCH resist diet induced obesity; when placed on a HF diet MCH-KO demonstrate and additional increase in resting energy expenditure as well as increased locomotor activity. The aims of this grant are to use this mouse model which lacks MCH to examine the role of MCH in modulate sympathetic activity and dopaminergic signaling. |
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| 2006 — 2010 | Maratos-Flier, Eleftheria | 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. |
Actions of Melanin Concentrating Hormone in the Brain @ Beth Israel Deaconess Medical Center DESCRIPTION (provided by applicant): Obesity is a serious illness, with a complex etiology, which is associated with increased risk in the development of multiple other morbidities including Type II diabetes, cardiovascular disease, hypertension and some neoplasias. In the United States, rates of obesity have been increasing and at present more than 50% of the population are either overweight or obese. The causes of obesity are poorly understood, however it is clear that molecular signaling pathways in the brain are important as rare cases of human obesity are caused by defective signals in these pathways. We have found that one neuropeptide, melanin-concentrating hormone (MCH), is an important regulator of energy balance and have reported that genetic ablation of MCH leads to a lean phenotype. Furthermore mice lacking MCH (MCH-/-) are resistant to diet induced obesity. Similarly, others reported that ablation of the rodent MCH receptor, MCHR-1, also leads to leanness. We have also found that MCH overexpression is associated with increased adiposity. We generated a model lacking both the MCH gene and leptin, MCH-/- ob/ob, which provided significant insights into the mechanisms by which MCH regulates body weight. In addition to effects on feeding MCH appears to have effects on energy expenditure and locomotor activity. In this proposal we will complete our characterization of the abnormalities of the MCH-/- ob/ob compared to ob/ob animals. Furthermore we will explore the hypothesis that we developed that MCH acts to suppress autonomic activity by evaluating nor-epinephrine turnover in mice lacking MCH as well as mice lacking both MCH and leptin. We will directly test the hypothesis that MCH mediates effects of leptin on sympathetic activity by examining NE turnover in normal and MCH-/- MCH-/- ob/ob and amice. We will also examine the hypothesis that we have developed that MCH acts to regulate dopaminergic signaling. To do this we will assess Dl and D2 dopamine receptors, dopamine transporters and dopamine levels in MCH-/-, MCH -/- ob/ob mice and compare these to wild type mice. We will evaluate behavioral responses to pharmacologic agents mediated through dopaminergic pathways. We will also perform microdialysis experiments to evaluate dopamine activity in freely moving mice in real time. Understanding these pathways will help understand mechanisms by which humans gain excess weight and are important in developing treatments for the prevention and treatment of obesity. |
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| 2007 | Maratos-Flier, Eleftheria | S10Activity Code Description: To make available to institutions with a high concentration of NIH extramural research awards, research instruments which will be used on a shared basis. |
@ Beth Israel Deaconess Medical Center [unreadable] DESCRIPTION (provided by applicant): Echo MRI-100(tm) 3-in-1 Obesity is a problem with increasing impact on human health and at present more than 60% of the population in the U.S. is either frankly obese or overweight. Despite the prevalence of this problem there are few effective treatments. Mouse models have provided valuable insights into understanding pathways important in the development of human obesity. This includes understanding both molecular pathways and the effects of dietary induced obesity. Analysis of mouse models requires technical capacity to evaluate body composition, particularly adiposity. The technology currently available to the group of obesity researchers at the BIDMC division of Endocrinology has significant limitations. Acquisition of the requested EchoMRI 3-in-1 will bypass this limitation and enhance ability to perform studies and also decrease the size of cohorts required. In addition this equipment will provide a heretofore unavailable capacity to evaluate composition of tissue samples, either from rodents or from human biopsy samples. Because of the capacity of the equipment, in addition to projected significant use by BIDMC Endocrine faculty and their collaborators the service can be offered to other BIDMC investigators. [unreadable] [unreadable] [unreadable] |
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| 2008 | Maratos-Flier, Eleftheria | 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. |
Clinical Trial: Exenatide and Body Weight in Obese Non-Diabetic Women @ Beth Israel Deaconess Medical Center Body Weight; CRISP; Clinical Trials; Clinical Trials, Unspecified; Computer Retrieval of Information on Scientific Projects Database; Cross-Over Studies; Cross-Over Trials; Crossover Studies; Crossover Trials; Diabetes Mellitus; Double-Blind Method; Double-Blind Study; Double-Blinded; Double-Masked Method; Double-Masked Study; Energy Expenditure; Energy Metabolism; Ex4 peptide; Exendin 4; Funding; Grant; Institution; Investigators; Metabolic; NIH; National Institutes of Health; National Institutes of Health (U.S.); Obesity; PBO; Placebos; Randomized; Research; Research Personnel; Research Resources; Researchers; Resources; Satiation; Satiations; Sham Treatment; Sleep; Source; Treatment Period; United States National Institutes of Health; Week; Weight; Woman; adiposity; blood glucose regulation; clinical investigation; corpulence; corpulency; corpulentia; diabetes; exenatide; glucose control; glucose homeostasis; glucose regulation; non-diabetic; nondiabetic; obese; obese people; obese person; obese population; randomisation; randomization; randomly assigned; satiety; sham therapy; treatment days; treatment duration |
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| 2008 | Maratos-Flier, Eleftheria | 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. |
Potential Regulation of Fgf-21 by Fasting and Diet-Induced Ketosis @ Beth Israel Deaconess Medical Center 21+ years old; Adult; Beta Cell; Blood; CRISP; Computer Retrieval of Information on Scientific Projects Database; D-Glucose; Dextrose; Diabetes Mellitus; Diet; Exposure to; FGF-21; FGF21; Fasting; Funding; Gastrointestinal Tract, Pancreas; Glucose; Grant; Human; Human, Adult; Human, General; In Vitro; Institution; Insulin Cell; Insulin Secreting Cell; Intermediary Metabolism; Investigators; Keto Sugars; Ketoses; Ketosis; Lipids; METBL; Mammals, Mice; Man (Taxonomy); Man, Modern; Metabolic; Metabolic Processes; Metabolism; Mice; Modeling; Monkeys; Murine; Mus; NIH; National Institutes of Health; National Institutes of Health (U.S.); Pancreas; Pancreatic; Physiologic; Physiological; Play; Regulation; Research; Research Personnel; Research Resources; Researchers; Resources; Reticuloendothelial System, Blood; Role; Source; United States National Institutes of Health; adult human (21+); diabetes; fasted; fasts; fibroblast growth factor 21; improved; improved functioning; response; social role |
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| 2011 — 2017 | Flier, Jeffrey S Maratos-Flier, Eleftheria |
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. |
@ Beth Israel Deaconess Medical Center DESCRIPTION (provided by applicant): PROJECT SUMMARY/ABSTRACT: Over the past two decades there has been a worldwide increase in the prevalence of obesity. In the United States 60% of the population is either overweight or obese. As a result, rates of obesity related co-morbities, particularly type II diabetes are increasing. Furthermore due to rising rates of obesity in the young, type II diabetes is now seen even in adolescence patients. This creates a demand for more and better therapeutic agents, potentially focused on novel pathways. Recently, FGF21 has emerged as a hepatic regulatory factor that acts on multiple remote targets including white adipose tissue but importantly also mediates effects on the liver itself in an autocrine fashion. We have found that FGF21 is an essential mediator of fatty acid oxidation in the liver, during ketosis, both in animals consuming a very low carbohydrate ketogenic diet and during fasting; others have reported improvements in glucose homeostasis in obese animals treated with FGF21 infusions. However, much remains to be elucidated regarding the biology of FGF21. The aims of this grant are to investigate the physiology and action of FGF21 both to improve our understanding of this hormone and to better assess the therapeutic potential of FGF21 as a future treatment of obesity and diabetes. To achieve this goal, we propose several lines of experimentation. In specific aim 1 we will evaluate the role FGF21 to regulate both glucose homeostasis and fatty acid oxidation during fasting. In addition we will generate two mouse models to determine the role of FGF21 in different tissues. In the second aim we will expand our work on obesity as FGF21 resistant state by exploring potential mechanisms that contribute to resistance which we have documented in both fat and liver. In this aim we will also evaluate the role of dual specificity phosphatases (DUSPs) in modulating FGF21 action. In the third specific aim we will focus on our recent finding that FGF21 acts on both brown adipose tissue and white adipose tissue in a manner suggesting a role to promote energy expenditure. In the fourth aim we will examine central effects of FGF21 and map target areas of the CNS that mediate these effects. |
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