1987 — 1989 |
Baskin, Denis G. |
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. |
Brain Insulin-Like Growth Factor Somatomedin Receptors @ University of Washington
The long range goal of this research is to understand the role of the brain in the regulation of growth. A variety of common metablic disorders, such as diabetes mellitus, malnutrition, and obesity, are accompanied by growth deficiencies thought to be associated with abnormal secretion of insulin-like growth factor-I (IGF-I) by the liver. An unsolved problem is how IGF-I inhibits the secretion of GH by a feedback mechanism operating in the brain. IGF-I inhibits GH secretion by acting directly on the pituitary gland, but evidence indicates that this negative feedback operates also at the level of the hypothalamus, where it is thought to stimulate the release of the GH inhibitory hormone, somatostatin (or somatotropin release inhibitory factor, SRIF). The mechanism involved in the regulation of GH secretion by IGF-I at the level of the brain is unknown, however. Recent data indicating that IGF-I receptors are present in the median eminence (ME) raises the hypothesis: IGF-I receptors inthe ME regulate SRIF secretion into the hypophyseal portal blood in the ME. The proposed experiments are designed to investigate three specific aims that address this hypothesis: (1) To determine if IGF-I receptors are located on the terminals of axons containing SRIF in the ME; (2) To determine if IGF-I receptors in the ME become more numerous (upregulate) in association with metabolic conditions accompanied by low plasma IGF-I levels; (3) To determine if regulation of IGF-I receptors in the ME changes the senitivity of SRIF release to IGF- I. The method used to measure binding of labeled IGF-I in the ME will be quantitative autoradiography (QAR): (a) microscopic quantitation of autoradiographic grain density in the ME after in vivo injection of labeled IGF-I into plasma; (b) computer image analysis of autoradiographic images of rat brain images on LKB film, produced by in vitro labeling of brain slices with labeled IGF-I. Binding sites for IGF-I (and the related peptide, IGF-II) in the ME and brain will be measured and characterized by QAR to determine specficity for IGF's analogues and verify receptor status, and to determine if ME IGF-I receptors undergo homeostatic changes in binding. Blood from the ME will be collected in experiments designed to test whether changes in ME IGF-I receptors are associated with increased sensitivity of ME SRIF release to plasma IGF-I levels. These results will support the hypothesis that IGF-I interacts with IGF-I receptors in the ME to control the release of SRIF into hypophyseal portal blood.
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1989 |
Baskin, Denis G. |
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. |
Insulin-Like Growth Factor Receptors in Human Retina @ University of Washington
The goals of the proposed research are to identify specific cell types which possess receptors for insulin-like growth factors (IGF's) in the human retina and to determine if binding of IGF-I and IGF-H to these cells is abnormal in diabetic retinopathy. The overall hypothesis is that vascular IGF receptors are abnormally regulated in diabetetic retinopathy (DR). The present proposal is part of a plan to change the direction of my research program to a major emphasis on vision research, particularly in relation to diabetes and metabolism. 1(GF-I and -II receptors are present in the brain but the distribution of IGF receptors among the different cell types in the intact retina is unknown. Our preliminary results on bovine and rat retinas show that IGF-II receptors are concentrated in the retinal pigment epithelium, choroid, and sclera whereas IGF-I receptors are found mainly in the neural retina aid choroid. The proposed research is a high risk pilot study aimed at determining if IGF binding to specific vascular or neural cells is altered in DR. Specific Aim No.1 addresses the question: "Which cells in the retina possess receptors for IGF's?" The methods will involve: (a) autoradiography of 125I-IGF-I and -II binding sites; (b) immunostaining with IGF receptor antibodies, esp. the widely used a-IR3 monoclonal antibody against the human IGF-I receptor for IGF-I receptors and the R- II-PAB1 polyclonal antiserum against the rat IGF-11 receptor (binds to human IGF-II receptor); (c) electron microscopic (EM) studies with biotinylated IGF'S, and EM immunostaining with the anti-receptor antibodies. Specific Aim No. 2 addresses the question, "Are there changes in numbers, location, or binding properties of IGF receptors associated with specific cell types of the retina in diabetic retinopathy?" We will use retinas from DR donors (both sexes, ages 45-70) obtained from the Lions Eye Bank, U.W. The vascular changes associated with DR eventually affect most individuals with diabetes and lead to blindness or visual impairment in a high proportion of diabetics with DR.The primary causes of basement membrane thickening in retinal microvessels, retinal capillary proliferation and the breakdown of the endothelial cell barrier and pericyte function in DR are unknown. The proposed research on retinal growth factor receptors will improve our understanding of the cellular abnormalities in the retina of patients with diabetic retinopathy.
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1996 — 2002 |
Baskin, Denis G. |
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. |
Core--Cytohistochemistry Facility @ University of Washington
histochemistry /cytochemistry; diabetes mellitus; biomedical facility; clinical research; tissue /cell preparation; autoradiography; photomicrography; electron microscopy; image processing; in situ hybridization; immunocytochemistry; human tissue;
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1996 — 2002 |
Baskin, Denis G. |
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 and Feasibility Studies @ University of Washington
health science research; diabetes education; diabetes mellitus;
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2003 — 2007 |
Baskin, Denis G. |
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. |
Cytohistochemistry Core @ University of Washington
Description (Provided by applicant) The Cytohistochemistry Core provides state-of-the-art technical support, facilities, and collaborative expertise for histochemical and morphological methods needed by DERC Affiliate Investigators. Cytohistochemistry Core services and facilities include tissue fixation, paraffin and cryostat tissue processing, histological and histochemical staining, immunocytochemistry, in situ hybridization, autoradiography, photomicrography and computer imaging, electron microscopy, and quantitative morphometric analysis. The Cytohistochemistry Core Director, Dr. Denis G. Baskin, is an established scientist in the fields of histochemistry and diabetes/endocrinology research. He is Research Professor of Medicine at the University of Washington and is also Senior Research Career Scientist in the VA Medical Research Service. The Core Director collaborates with DERC Affiliate Investigators and oversees the operations of the Core. In response to DERC Affiliate requests for electron microscopy Core support, the Cytohistochemistry Core recruited Dr. Thomas Wight to the position of Associate Core Director. Dr. Wight, a prominent cell biologist in the area of vascular biology and extracellular matrix, oversees the electron microscopy services of the Core, including a part-time technician. Charge backs are assessed to Core users to offset the cost of Core services. The Cytohistochemistry Core is a cost-efficient resource for a large group of DERC investigators and has been successful over the years in contributing to numerous publications by Affiliate Investigators. Going into the new funding period, the Cytohistochemistry Core has requests for service by 37 Affiliate Investigators for 40 projects, all with peer-reviewed grant support. The DERC also proposes to add a laser capture microdissection system to the Cytohistochemistry Core to provide Affiliates with the capability of obtaining microscopic samples of tissues and cells for molecular and biochemical analysis related to diabetes.
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2003 — 2007 |
Baskin, Denis G. |
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 and Feasibiliy Program @ University of Washington
Description (adapted from the application) Eligibility: The research supported by the Pilot and Feasibility Studies Program is primarily intended to be a first grant for junior faculty at the U Washington who have not yet obtained a major peer-reviewed grant (such as an R01 or K21) in the areas of diabetes or endocrinology. Senior faculty members are also eligible to apply if their projects represent first entry into the field of diabetes research. Established investigators in diabetes are also eligible if their purpose is to test innovative ideas that truly represent a clear departure from previous research activity. Any single investigator is eligible to receive a P and F award only once, unless the second P and F is a clear departure from the research area of the original award. Funding level: Since NIH funding to our DERC P and F Studies Program has been $50,000 per year for all P and F projects combined, up to now there has been limited support for each project to a maximum of $25,000 yearly. Awards are made initially for one year, but a second year?s funding is provided if satisfactory progress is made during the first year. Despite these limited funds, there has been a large response to calls for applications and numerous meritorious research projects have been supported. As a result of increased funding to the Diabetes Center for P and F studies, an increase in the funding level and the number of awards in the P and F program is proposed. It is intended that $200,000 of the new DERC budget be allocated to P and F research awards. Recipients must be members of the U. Washington faculty (postdoctoral fellows and research scientists are not eligible) and meet established criteria. The awards will be limited to $50,000 per year for 2 years but some may be smaller. The awards are made on the basis of scientific merit, following rigorous scientific review procedures that have been used in for past applications. New Investigator Awards: The DERC Studies Program also administers the Diabetes Investigator Award Program of $25,000 per year to members of the faculty who are making their first entry into diabetes research. These awards are supported to the private DRTP, an endowed fund of the UW to foster diabetes research. The eligibility and evaluation criteria are the same as the P and F program. Fellowships: The P and F program also administers the McAbee Fellowship Program that is also privately funded by the DRTP.
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2004 — 2008 |
Baskin, Denis G. |
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. |
Core--Histochemistry @ University of Washington
The Histochemistry Core provides state-of-the-art technical support, facilities, and collaborative expertise for histochemical and morphological methods needed by the principal investigators of this Program Project. Histochemistry Core services and facilities include tissue fixation and processing (including cryostat sectioning), histological and histochemical staining (e.g., lacZ), immunocytochemistry, fluorescence microscopy, image analysis, and laser capture microdissection. If necessary, the Histochemistry Core can provide in situ hybridization and confocal microscopy. The proposed Director of the Histochemistry Core is Dr. Denis G. Baskin, an established scientist in the fields of histochemistry and diabetes/endocrinology research. He is Research Professor of Medicine at the University of Washington and is also Senior Research Career Scientist in the Seattle VA Medical Center. Dr. Baskin will oversee the administrative and scientific activities of the Histochemistry Core and act as a collaborator on Program Project studies that utilize the core.
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2013 — 2015 |
Baskin, Denis G. |
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 and Feasibility Program @ University of Washington
The Pilot and Feasibility (P&F) Program of the Diabetes Research Center at the University of Washington promotes the development of new and innovative research directed at basic, clinical and translational aspects of diabetes. The specific objectives of the Program are to: (1) Provide initial research support for junior faculty who have not yet had independent peer-reviewed NIH funding; (2) Provide pilot funding for established faculty entering the field of diabetes research for the first time; (3) Support pilot projects by established diabetes investigators proposing to pursue a novel direction in their diabetes related research; and (4) Foster mentorqd training in research related to diabetes by offering postdoctoral and graduate fellowships. The P&F Program annually awards $200,000 ofthe Center's NIDDK direct funds (a minimum of 20%) for P&F research projects. In addition, funds provided by the University are used to support new investigator research, training of postdoctoral fellows and graduate students, and service grants for junior investigators to use the Center's resources. Applications are peer-reviewed by external and internal reviewers and the Center's Executive Committee, with awards being made based on scientific merit and qualifications ofthe applicant, including the potential for subsequent external peer-reiviewed funding. During the last decade (two funding cycles), NIDDK funds to the Diabetes Research Center at the University of Washington supported 33 P&F awards, the majority of which were awarded to junior faculty. Of these P&Ffunded investigators, 27 remain active in research related to diabetes, obesity and related disorders (82% success). Ofthe six that are no longer doing diabetes-related research, four are still in academic medicine doing research. Thus, the P&F Program continues to be a highly successful component of the Diabetes Research Center that utilizes funds provided by NIDDK and the University of Washington to support new and innovative research in the area of diabetes, obesity and related disorders, and in this manner also fosters the career development of junior investigators. RELEVANCE
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