Shuldiner, Alan R., MD
Genomics of Type 2 Diabetes: Moving beyond GWAS to Mechanisms and Genome-informed Personalized Medicine
General Research Subject: Type 2 Diabetes
Focus: Clinical Therapeutics/New Technology, Clinical Therapeutics/New Technology\Pharmacologic Treatment of Diabetes or its Complications, Genetics, Genetics\Type 2 Diabetes, Integrated Physiology, Integrated Physiology\Insulin Resistance
Type of Grant: Mentor Based Postdoctoral Fellowship
Project Start Date: July 1, 2012
Project End Date: June 30, 2016
Recently genome-wide approaches have unveiled common variations in a number of genes that increase susceptibility to T2D. Dr. Shuldiner and his group at the University of Maryland School of Medicine have made important contributions to this field studying the Old Order Amish, a genetically homogeneous population ideal for genetic studies. Now that these genetic variations have been discovered, the goal of our research is to understand the mechanism(s) by which they increase susceptibility to T2D and to use this new knowledge to design more targeted and effective interventions to prevent or treat it. This proposal is to support the mentoring and training of post-doctoral fellows in clinical and translational diabetes genomics research.
Since 1990, Dr. Shuldiner has mentored 21 predoctoral students, 30 postdoctoral trainees and 14 junior faculty. His multidisciplinary research program offers trainees an outstanding research environment to acquire the intellectual and technical skills necessary for a successful career in diabetes research. Ijeoma Muo, MD, MPH, the first postdoctoral fellow proposed for this award, is a well-trained African American physician with interest in the treatment and prevention of diabetes and obesity. This ADA Mentored Postdoctoral Fellowship award will allow Dr. Muo to immerse in full-time clinical and translational research, which will equip her with the knowledge, experience and technical skills to become a successful independent investigator. In addition to the training of future generations of diabetes researchers, these studies promise to uncover novel mechanisms of disease and potentially new approaches for treatment and prevention of diabetes and its complications.
Mentor: Alan Shuldiner, MD
Postdoctoral Fellow: Stephanie Stein, MD
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
Working with the Old Order Amish, a genetically homogeneous founder population, we have published genome-wide linkage scans for type 2 diabetes (T2D) and metabolic syndrome traits, and were among the first to apply genome-wide association studies (GWAS) to discover novel genes and loci for T2D, coronary calcification, blood pressure, serum lipid, and uric acid levels, and response to the anti-platelet agent clopidogrel (Plavix). We now seek to understand the underlying mechanisms whereby these loci/genes confer increased risk, and the development of innovative genome-informed approaches to treatment and prevention. Post-doctoral fellows will have the opportunity to perform clinical and translational research, studying subjects with specific genotypes of interest, and performing hypothesis-driven phenotyping to elucidate underlying mechanisms whereby gene variants exert their pathophysiological effects. Projects include studies to elucidate the mechanisms whereby genetic variants in growth receptor bound 10 (GRB10) increase risk for T2D; the effect of zinc supplementation on insulin secretion and diabetes treatment and prevention in subjects with SLC30A8 T2D susceptibility variants; how a mutation in hormone sensitive lipase gene (LIPE) causes diabetes; and pharmacogenomics of anti-platelet agents in cardiovascular disease. These studies may lead to new insights into the genetic underpinnings of T2D and its cardiovascular complications, which may result in new diagnostic and prognostic markers and novel targets for therapy and prevention.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
T2D runs in families and thus has a genetic component. Using genetic approaches, we aim to learn more about the underlying cause of T2D and its cardiovascular complications. These understandings may lead to new tests to better classify diabetes and to develop more effective individualized approaches to prevent or treat the disease and its cardiovascular complications.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
My interest is in the genetics of common adult-onset diseases such as diabetes and its cardiovascular complications. This grant will provide the opportunity for me to continue to mentor the most promising post-doctoral fellows and to train the next generations of independent academic clinical and translational scientists.
In what direction do you see the future of diabetes research going?
As we understand more about what causes diabetes and its complications, we will learn that diabetes is a heterogeneous disorder caused by multiple factors. Based upon new understandings from gene discoveries, we will be able to subclassify different underlying biological causes of diabetes which will allow physicians to individualize therapy and prevention. Individualized therapy based upon a patient’s genetic makeup and other factors will include personalized lifestyle and medication recommendations which will be much more effective in treating or preventing diabetes and its complications.
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