Project Grant K23DK140643
- This Project Grant award from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), provides $882,180 to support a study on genetic risk assessment for monogenic and common forms of diabetes. The Broad Institute, Inc. will lead this 5-year research project to analyze the largest-ever dataset of over 1.1 million participants (33% non-European) to assess the penetrance of rare...
- This federal Project Grant award of $583,732, provided by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), supports research on molecular prediction, disease progression, and type 2 diabetes (T2D) phenotypes in South Asian populations. The research aims to: (1) investigate genetic associations with T2D and prediabetes phenotypes, develop polygenic risk scores, and explore the...
- This federal Cooperative Agreement award, with a total funding amount of $1,207,770.00 and an award date of January 1, 2025, was granted by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847). The award will support research to investigate the role of genetically-controlled thymic epithelial cell (TEC) and hematopoietic stem cell (HSC) abnormalities in driving the development...
- This $801,662 Project Grant award from the National Institute of Diabetes and Digestive and Kidney Diseases (CFDA 93.847 - Diabetes, Digestive, and Kidney Diseases Extramural Research) to the Scripps Research Institute supports research to characterize antigen-presenting cells (APCs) associated with pancreatic islets and their role in the initiation of type 1 diabetes (T1D) autoimmunity. The research aims to define the landscape of CD45+ and CD45- APCs in normal pancreatic islets and those...
- This Project Grant award of $455,491 from the National Institute of Diabetes and Digestive and Kidney Diseases (CFDA 93.847 - Diabetes, Digestive, and Kidney Diseases Extramural Research) supports research by the University of North Carolina at Chapel Hill (UNC-CH) to investigate the role of T follicular helper cells (Tfh) in regulating T cell-mediated autoimmunity in type 1 diabetes. The research aims to: 1) characterize changes in islet Tfh cells as type 1 diabetes progresses, 2) define the...
- This Project Grant award from the National Institute of Allergy and Infectious Diseases (CFDA 93.855 - Allergy and Infectious Diseases Research) is providing $287,000 to The Regents of the University of California, San Francisco (UCSF) to conduct research on whether genetic mutations that alter IL-17 signaling contribute to the development of autoimmune diabetes. The objective is to determine if rare genetic variants in the IL17RC and IL17C genes, which were identified in families with a history...
- This $156,982 Project Grant award from the National Institute of Diabetes and Digestive and Kidney Diseases (CFDA 93.847 Diabetes, Digestive, and Kidney Diseases Extramural Research) supports a 5-year research project led by Dr. Mary Rooney at the Johns Hopkins Bloomberg School of Public Health. The project aims to refine prediabetes definitions and improve prediction of diabetes and its complications using clinical factors, novel proteomic biomarkers, and polygenic risk scores. Key activities...
- This Cooperative Agreement award of $1,786,925 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), supports research to investigate the role of inefficient RNA editing in triggering an innate immune response that leads to beta cell death and the onset of type 1 diabetes (T1D). The project aims to evaluate three potential pathways by which insufficient adenine to inosine...
- This Project Grant award from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), aims to provide resources to interpret genetic signals and multi-tissue mechanisms for type 2 diabetes and related traits. The $1,620,238 award to the University of North Carolina at Chapel Hill (UNC-CH) will support the detection of regulatory variants and elements at type 2 diabetes...
- This Cooperative Agreement award from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), provides $843,179 to Weill Medical College of Cornell University to conduct research aimed at "Decoding the Cell-Specific Impact of Epigenomic and Alternative Splicing Regulation During T1D Progression". The project aims to use single-cell multi-omic profiling, human...
MULTI-ANCESTRY GENETIC ANALYSIS OF TYPE 1 DIABETES AND RELATED CONDITIONS - PROJECT SUMMARY/ABSTRACT TYPE 1 DIABETES (T1D) IS A HIGHLY PREVALENT DISORDER AFFECTING OVER 8 MILLION INDIVIDUALS WORLDWIDE. T1D CAUSES SIGNIFICANT MORBIDITY AND MORTALITY, INCLUDING ACUTE COMPLICATIONS SUCH AS DIABETIC KETOACIDOSIS AS WELL AS CHRONIC COMPLICATIONS SUCH AS NEPHROPATHY, NEUROPATHY, RETINOPATHY, AND CARDIOVASCULAR DISEASE. DEVELOPING A DEEPER UNDERSTANDING OF T1D RISK FACTORS IS CRITICAL TO REDUCE DIABETES-RELATED COMPLICATIONS, TO IDENTIFY INDIVIDUALS AT HIGH RISK FOR T1D, AND POTENTIALLY TO DELAY OR TO PREVENT THE ONSET OF T1D. BECAUSE T1D IS CHARACTERIZED BY AUTOIMMUNE DESTRUCTION OF INSULIN-PRODUCING BETA CELLS, T1D RISK IS STRONGLY INFLUENCED BY GENETIC VARIANTS RELATED TO IMMUNE FUNCTION. GENETIC RISK FOR T1D CAN BE QUANTIFIED WITH A POLYGENIC SCORE, WHICH INTEGRATES THE DISEASE RISK OF CAUSAL VARIANTS FROM ACROSS THE GENOME. CURRENT POLYGENIC SCORES HAVE DEMONSTRATED EXCELLENT PREDICTIVE POWER TO IDENTIFY THOSE INDIVIDUALS MOST LIKELY TO DEVELOP T1D. HOWEVER, MOST EXISTING SCORES WERE DEVELOPED AND VALIDATED IN INDIVIDUALS WITH EUROPEAN GENETIC ANCESTRY, AND THEIR PREDICTIVE POWER DECLINES WHEN APPLIED TO OTHER POPULATIONS. IN THIS PROPOSAL, WE WILL DEVELOP A MULTI-ANCESTRY T1D POLYGENIC SCORE THAT INTEGRATES GENETIC VARIANTS FROM DIVERSE ANCESTRAL POPULATIONS. WE WILL APPLY THIS SCORE TO PREDICT RISK FOR T1D AS WELL AS FOR CERTAIN ATYPICAL IMMUNE-MEDIATED FORMS OF DIABETES, WHICH MAY SHARE GENETIC RISK FACTORS WITH T1D. ADDITIONALLY, WE WILL APPLY COMPUTATIONAL METHODS THAT ANALYZE T1D GENETIC RISK FACTORS TO IDENTIFY GENETIC SUBTYPES OF T1D. THE PROPOSED PROJECT WILL PROVIDE ADVANCED TRAINING IN COMPUTATIONAL BIOLOGY AND STATISTICAL GENETICS. THE RESEARCH SETTING REPRESENTS AN IDEAL ENVIRONMENT FOR JUNIOR INVESTIGATORS, COMBINING THE WORLD-CLASS CLINICAL EXPERTISE OF MASSACHUSETTS GENERAL HOSPITAL WITH THE INNOVATIVE COMPUTATIONAL RESOURCES OF THE BROAD INSTITUTE. THIS PROJECT WILL PROVIDE A FOUNDATION FOR THE CANDIDATE TO APPLY FOR INDEPENDENT RESEARCH FUNDING AND ULTIMATELY TO ESTABLISH A CAREER AS A PHYSICIAN SCIENTIST.
Mod # | Description | ReasonForModification | Federal Obligation | Date |
|---|---|---|---|---|
| Not listed | $191.9k | 4/29/25 | ||
| Not listed | $191.8k | 7/24/24 | ||
| Not listed | $191.8k | 7/24/24 |