Laughlin Initiatives in Diabetes

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Diabetes, Obesity & Metabolism Research in the Early 21st Century* (*from the NIH Point of View): 

Diabetes, Obesity andamp; Metabolism Research in the Early 21st Century* (*from the NIH Point of View) December, 2004 Maren R. Laughlin, Ph.D. Senior Advisor for Integrative Metabolism National Institute of Diabetes andamp; Digestive and Kidney Diseases National Institutes of Health

Three Major Areas of Interest: 

Three Major Areas of Interest Diabetes andamp; Metabolic Disease NIDDK, NHLBI, NIA, NICHD, NIAID, NCI, NIBIB, etc. Obesity Trans-NIH http://www.obesityresearch.nih.gov/ http://www.niddk.nih.gov/welcome/org/OD/OOR/OOR.htm NIH Roadmap Trans-NIH www.nihroadmap.nih.gov

Diabetes & Metabolic Disease* (*from the NIH Point of View): 

Diabetes andamp; Metabolic Disease* (*from the NIH Point of View) Type 2 Diabetes Incidence: ~18M Americans Healthcare burden: $132B in 2002 Recently found in children and young people as well as older adults Major focus of NIDDK research efforts Type 1 Diabetes Special Statutory Funding Program for Type 1 Diabetes Research http://www.niddk.nih.gov/fund/diabetesspecialfunds/funding.htm $1.14 billion for FY 1998 - FY 2008 Diabetic Complications Common to type 1 and type 2 diabetes Heart disease/atherosclerosis, microvascular disease / neuropathy, retinopathy, nephropathy

Multi-pronged Approach to Diabetes Research: 

Multi-pronged Approach to Diabetes Research Investigator Initiated Grants Treatment and Prevention Trials Epidemiology Genetics studies Requests for Applications: NIH Initiated Grants Resources, such as Animal models Tissue sources Standards Reagents and technologies Community Organization (consortia, collaberations, workshops, etc) Training

Type 2 Diabetes Resources: 

Type 2 Diabetes Resources Diabetes Centers: DERCs and DTRCs Provides core resources to foster interdisciplinary research in diabetes and related areas International Type 2 Diabetes Linkage Analysis Consortium Mouse Metabolic Phenotyping Centers (MMPC) Mice are shipped to a Center for in-depth phenotyping Nuclear Receptor Signaling Atlas to gather and organize information relating to key aspects of orphan nuclear receptor biology

Type 1 Diabetes Resources cont’d.: 

Type 1 Diabetes Resources cont’d. Islet Cell Resource Centers (ICR) Human Pancreatic Islets Available for Non-Clinical Research ($0.10 / islet) Availability of pancreas-specific microarrays Mouse PancChip 5.0 and Human PancChip 1.0 Beta Cell Biology Consortium Reagents for study of islet development andamp; cell replacement therapies

Type 1 Diabetes Resources: 

Type 1 Diabetes Resources Collaborative Projects on Proteomics andamp; Metabolomics For Type 1 Diabetes andamp; its Complications Clearinghouse for tissue samples for proteomics/metabolomics analysis www.niddk.nih.gov/fund/diabetesspecialfunds/proteomics/ Access to samples from major clinical trials (DCCT, DPP) Type 1 Diabetes-Rapid Access to Intervention Development (T1D-RAID) Resources to aid in pre-clinical development of new drugs Type 1 Diabetes Mouse Repository at the Jax Labs Animal Models of Diabetic Complications Consortium Mice and pig models

Growth in Basic Biology Programs: 

Growth in Basic Biology Programs Beta cell developmental biology: (stem cells and transcription factors, toward cell therapy) Islet transplantation and engineering Imaging the pancreatic beta cell Adipocyte as endocrine organ Immunology of diabetes Mechanisms of insulin resistance Neurobiology of energy balance Proteomics and metabolomics of diabetes: Biomarkers of disease Diabetic Complications Hypoglycemia unawareness Molecular mechanisms

Current & Future Diabetes Initiatives: 

Current andamp; Future Diabetes Initiatives Current: RFA-DK-04-022 receipt: March 17, 2005 Collaborative Studies on Angiogenesis and Diabetic Complications RFA-DK-05-001 receipt: February 24, 2005 Preventing Mitochondrial Oxidative Stress in Diabetes and Obesity Coming Soon: Beta Cell Regeneration for Diabetes Therapy (RFA) Pilot and Feasibility Program in Human Islet Biology (RFA) Mouse Metabolic Phenotyping Centers (RFA)

Special Emphasis Program Announcements: 

Special Emphasis Program Announcements PA-04-092 Long-Term Weight Maintenance: Basic and Clinical Studies PA-04-088 Non-Invasive Methods for Diagnosis and Progression of Diabetes, Kidney, Urological, Hematological , and Digestive Diseases PA-04-081 Proteomics: Diabetes, Obesity, and Endocrine, Digestive, Kidney, Urologic, and Hematologic Diseases PAR-04-078 Ancillary Studies to Major Ongoing NIDDK Clinical Research Studies PA-04-074 Health Disparities in NIDDK Diseases PA-04-068 Development Assays for High Throughput Drug Screening PA 04-033 Diet Composition and Energy Balance

Diabetes Program Announcements: 

Diabetes Program Announcements PA 03-052 Proteomics in Diabetes and Other Endocrine and Metabolic Diseases PA 02-077 Secondary Analyses in Diabetes, Digestive and Kidney Diseases PA03-0156 Insulin Signaling and Receptor Cross-Talk PA-04-033 Diet Composition and Energy Balance PA-04-098 Heterogeneity of Fat Depots: Underlying Basis and Association with Morbidity PA 03-150 Erythroid Lineage Molecular Toolbox PA 03-145 Ubiquitin and Ubiquitin-Like Modification Regulating Disease Processes PA 02-161 Development of the Endocrine Pancreas PA 02-117 Racial andamp; Ethnic Differences in the Etiology of Type 2 Diabetes in United States PA 01-117 Liver and Pancreatic Disease in HIV Infection PA 01-112 The Role of Antioxidants in the Prevention of Diabetic Complications PA 02-100 Complex Formation in Hormonal Regulation of Gene Expression PA 02-094 Ancillary Studies on Control Groups in Clinical Trials

NIDDK Initiative Concepts for 2006: 

NIDDK Initiative Concepts for 2006 Development of Biomarkers for Disease Animal Models of NIDDK-Relevant Diseases Imaging Fibrosis in Kidney, Liver and Bladder Potential Therapeutic Agents for Diseases of Protein Misprocessing or Misfolding Genetic Longitudinal Studies of Obesity-Related Phenotypes Translation of Invertebrate Obesity Genetics to Mammals Planning or Implementation of New Clinical Studies of Interest to NIDDK

Obesity Research (from the NIH Point of View): 

Obesity Research (from the NIH Point of View) NIH Obesity Taskforce established April, 2003 25 ICs and offices, co-chaired by the Directors of NIDDK and NHLBI http://www.obesityresearch.nih.gov/ Strategic Plan: Research toward preventing and treating obesity through lifestyle modification. Research toward preventing and treating obesity through pharmacologic, surgical, or other medical approaches. Research toward breaking the link between obesity and its associated health conditions. Cross-cutting research topics, including health disparities, technology, fostering of interdisciplinary research teams, investigator training, translational research and education/outreach efforts.

NIDDK Office of Obesity Researchhttp://www.niddk.nih.gov/welcome/org/OD/OOR/OOR.htm: 

NIDDK Office of Obesity Research http://www.niddk.nih.gov/welcome/org/OD/OOR/OOR.htm 'Right hand' of NIH Obesity Task Force comprised of NIDDK staff serves to assist the Director, NIDDK in identifying research opportunities, initiatives, and advances identify and plan appropriate workshops and conferences

Clinical Trials in Obesity: 

Clinical Trials in Obesity Action to Control Cardiovascular Disease Risk in Diabetes (ACCORD) test best ways to lower risk of heart disease and stroke in adults with type 2 diabetes BARI 2 Bypass Angioplasty Revascularization Investigation 2 Diabetes Determine the best therapies for people with type 2 diabetes and heart disease Longitudinal Assessment of Bariatric Surgery (LABS) conducting coordinated clinical, epidemiological, and behavioral research in the field of bariatric surgery SEARCH for Diabetes in Youth Study determine the prevalence of diabetes in children in six areas of the U.S. and help clarify trends in the development of diabetes in youth TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) identify the best treatment of type 2 diabetes in children and teens

Clinical Samples for Obesity & Diabetes Researchers: 

Clinical Samples for Obesity andamp; Diabetes Researchers NIDDK Central Repositories: Biosamples, Genetics, Data Established to store biosamples and data collected in designated NIDDK-funded clinical studies. Purpose is to expand the usefulness of these studies by allowing a wider research community to access collected materials RFA-DK-03-022 receipt: July 19, 2005 Ancillary Studies to Obesity-Related Clinical Trials

Current Obesity Research Solicitations : 

Current Obesity Research Solicitations RFA-DK-05-0 receipt: February 24, 2005 Preventing Mitochondrial Oxidative Stress in Diabetes and Obesity RFA-HL-04-022 receipt: February 16, 2005  Bioengineering Approaches to Energy Balance and Obesity (measure energy balance, food intake, activity, etc.) PA-04-156 receipt:Feb 1, June 1, Oct 1 Bioengineering Approaches to Energy Balance and Obesity (SBIR/STTR) RFA-ES-04-003 receipt: Dec. 17, 2004 Obesity and the Built Environment RFA-DK-03-018 receipt: March 17, 2005 Genetic Studies of Obesity-Related Traits in Model Organisms (Drosophila, C elegans, zebrafish)

Obesity Program Announcements: 

Obesity Program Announcements Basic Research PA-04-124: Studies of Energy Balance and Cancer in Humans PA-04-098: Heterogeneity of Fat Depots: Underlying Basis andamp; Association with Morbidity PA-04-081: Proteomics: Diabetes, Obesity, and Endocrine, Digestive, Kidney, Urologic andamp; Hematologic Diseases PA-04-033: Diet Composition and Energy Balance

Obesity Program Announcements: 

Clinical and Behavior Research PA-04-092: Long-Term Weight Maintenance: Basic and Clinical Studies PAR-03-009: Improving Diet and Physical Activity Assessment PAR-04-082: Small Clinical Grants in Digestive Diseases, Nutrition and Obesity PA-04-121: Understanding Mechanisms of Health Risk Behavior Change in Children andamp; Adolescents PAR-03-060: Planning Grants for Translational Research for the Prevention and Control of Diabetes PA-02-153: Translational Research for the Prevention and Control of Diabetes PA-02-159: Enhancing Adolescent Health Promotion Across Multiple High Risk Behaviors PA-05-009: Research on the Economics of Diet, Activity, and Energy Balance PA-04-145: School-Based Interventions To Prevent Obesity Obesity Program Announcements

Recent NIH Obesity Workshops: 

Recent NIH Obesity Workshops Women and Obesity November 4, 2004 1-3 p.m. Obesity and the Built Environment: Improving Public Health Through Community Design May 24-26, 2004 Lipids and the Pathophysiology of Obesity May 10-11, 2004 From clinical trials to community: The science of translating diabetes and obesity research January 12-13, 2004 Adipose Tissue Secretory Function and Its Role in Obesity-Associated Co-Morbidities December 11-13, 2003 Phenotyping Obesity for Human Genetic Studies October 28-30, 2003

NIH Roadmap*(*from the NIH Point of View): 

NIH Roadmap* (*from the NIH Point of View) Theory NIH institutes working together to serve the unique needs of 21st century American biomedical science Practice Research themes, projects and resources that no one institute could support because of limited budgets and defined missions 28 initiatives andamp; 171 awards to date Resources $237M in FY05, projected to ~ $500M by FY09

The NIH Roadmap and Obesity: 

The NIH Roadmap and Obesity PI: JAY D. HORTON Title: Task force for Obesity Research at UT Southwestern RFA: Exploratory Centers for Interdisciplinary Research Goals: Taskforce combines neuroendocrinology, genetics, lipid metabolism, intermediary metabolism, and clinical epidemiology Brain regulation of food intake and energy expenditure Dysregulation of glucose and lipid metabolism in the liver

The NIH Roadmap and Obesity: 

PI: BARRY M. POPKIN Project Title: An Interdisciplinary Strategy for Obesity RFA: Exploratory Centers for Interdisciplinary Research Goals: Inter-Disciplinary Obesity Center (IDOC) Nutrition, epidemiology, health behavior, urban planning, health economics, physiology, psychology, genetics, and clinical medicine Find effective interventions for prevention and treatment of obesity The NIH Roadmap and Obesity

The NIH Roadmap & Metabolic Disease: 

The NIH Roadmap andamp; Metabolic Disease PI: HENRI BRUNENGRABER Title: Dynamic Metabolomics via Isotopomer Analysis RFA: Metabolomics Technologies Development Goals: Identify, measure and interpret the complex time-related concentration, activity and flux of endogenous metabolites instrumentation to increase sensitivity Carbon-labeled substrates and 2H2O to measure fluxes in metabolic networks via mass isotopomer analysis Models and multivariate statistics to provide new avenues for understanding metabolic diseases

NIH Roadmap Themes (& 13 Implementation Committees): 

NIH Roadmap Themes (andamp; 13 Implementation Committees) New Pathways to Discovery Building Blocks, Biological Pathways, and Networks Molecular Libraries andamp; Molecular Imaging Structural Biology Bioinformatics and Computational Biology Nanomedicine Research Teams of the Future High-Risk Research Interdisciplinary Research Public-Private Partnerships Re-engineering the Clinical Research Enterprise Clinical Research Networks/NECTAR Clinical Research Policy Analysis and Coordination Clinical Research Workforce Training Dynamic Assessment of Patient-Reported Chronic Disease Outcomes Translational Research

New Pathways to Discovery Projects: 

New Pathways to Discovery Projects SMALL MOLECULES Metabolomics Technology Development Projects tools to measure metabolites and their dynamic fluctuations within cells Molecular Libraries Screening Center Network (MLSCN) high throughput screening of chemically diverse small molecules (500,000) with the hope of providing new reagents for research (activators / inhibitors / markers) MOLECULAR IMAGING technologies and reagents for imaging of molecules or molecular events within single cells and whole organisms PROTEINS National Technology Centers for Networks and Pathways tools to measure the activity, translocation, and interactions of intracellular protein molecules Innovation in Membrane Protein Production Centers to prepare membrane proteins for structural studies

Research Teams of the Future Projects: 

Research Teams of the Future Projects HIGH RISK RESEARCH: 9 Pioneer Awards $500K/yr for 5 yrs to encourage creative, outside-the-box thinkers to pursue exciting and innovative ideas in biomedical research INTERDISCIPLINARY RESEARCH Exploratory Centers (P20) for Interdisciplinary Research Large series of training initiatives in IR TRANSLATIONAL RESEARCH RAID: Rapid Access to Intervention Development resources for pre-clinical development of drugs (toxicology, dosing, manufacture, etc.)

2005 RM Initiatives (from 16 total) http://nihroadmap.nih.gov/grants/index.asp: 

2005 RM Initiatives (from 16 total) http://nihroadmap.nih.gov/grants/index.asp Building Blocks, Biological Pathways RM-04-019 receipt 2/22/05 National Technology Centers for Networks and Pathways Molecular Libraries RM-04-027   receipt 3/10/05 Cheminformatics Research Centers RM-05-011   receipt 2/14/05 Assay Technology Development RM-05-014 receipt 2/15/05 Pilot-Scale Libraries for High-Throughput Screening   Structural Biology RM-04-026 receipt 1/24/05 Membrane Protein Production and Structure Determination

2005 RM Initiatives (cont’d.) http://nihroadmap.nih.gov/grants/index.asp: 

2005 RM Initiatives (cont’d.) http://nihroadmap.nih.gov/grants/index.asp Interdisciplinary Research RM-04-008 receipt 2/11/05 Short Programs for Interdisciplinary Research Training RM-05-010 receipt 2/11/05   Interdisciplinary Health Research Training: Behavior, Environment and Biology High Risk Research NIH Director's Pioneer Awards

Other Funding Mechanisms for Partnerships: 

Other Funding Mechanisms for Partnerships BRP Bioengineering Research Partnerships http://grants2.nih.gov/grants/guide/pa-files/PAR-04-023.html R24 Interactive Partnerships NIGMS or NIDDK Grantees, Collaboration between funded investigators $300K/yr for 4 yrs, non-renewable For consortium activities http://grants2.nih.gov/grants/guide/pa-files/PA-03-127.html

Contact Information: 

Contact Information Maren R. Laughlin, Ph.D. Senior Advisor for Integrative Metabolism NIDDK, NIH 6707 Democracy Blvd., MSC 5460 Bethesda, MD 20892 301-594-8802 Maren.laughlin@nih.gov www.nih.gov andamp; www.niddk.nih.gov

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