2014 Grant Recipients
Michael Dennis, PhD
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The Pennsylvania State University, Hershey, PA
Hyperglycemia-induced translational control of gene expression in the retina
Nearly all people with type 1 diabetes, and the majority with type 2, experience some degree of retinopathy in their lifetime. Unfortunately, treatments that fully address the molecular pathogenesis of this complication are presently lacking. The overall goal of this research project is to identify mechanisms that regulate hyperglycemia-induced expression of factors that control blood vessel growth and proliferation in the retina. This research strategy represents a new and fundamentally different approach to investigate the molecular players responsible for retinal neurovascular complications, and will allow validation of novel targets for intervention at the level of gene expression. This study may ultimately lead to the development of innovative, non-destructive therapies that address the cause of diabetic retinopathy.
Stephen Parker, PhD
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University of Michigan, Ann Arbor, MI
Deconstructing type 2 diabetes using genome-wide high-density multi-tissue 'omics' profiling
Susceptibility to type 2 diabetes is partly encoded in the genetic code, or DNA. Exactly how changes in DNA lead to diabetes susceptibility and progression, however, currently remains unclear. Recent studies suggest that most disease-associated genetic variations reside not within the coding regions of genes, but instead outside the genes—in regions generally referred to as regulatory elements. These elements control when, where, and how much a gene is turned on. This project is geared to identify these hidden regulatory elements and link them to the genes they control. Such information can lead to quantitative disease surveillance over time, and will help identify the next generation of type 2 diabetes drug targets. Integration of these results with a personal DNA code can help guide "custom" treatment strategies based on the specific combination of risk changes an individual may have.
Kathleen Page, MD
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University of Southern California, Los Angeles, CA
Neural mechanisms in maternal-fetal programming for obesity and diabetes
Exposure to environmental stressors early in life, such as prenatal exposure to diabetes, appears to contribute to the development of type 2 diabetes later in life. Animal studies suggest that fetal exposure to maternal diabetes may cause changes in brain pathways that help control body weight and blood sugar. The goal of our research is to use cutting edge neuroimaging techniques to characterize brain pathways involved in body weight and blood sugar control in children who were either exposed or unexposed to diabetes in utero. This project will identify early life markers in brain appetite pathways that may contribute to the development of obesity and type 2 diabetes. These newly identified markers can then be used to develop interventions to prevent obesity and diabetes in high-risk children. These studies could help find new ways to prevent diabetes in those at highest risk and to develop new ways to treat patients with diabetes.
Joshua Thaler, MD, PhD
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University of Washington, Seattle, WA
Modulating glial-neuronal interactions to treat obesity and diabetes
Therapies for diabetes have largely involved insulin: providing insulin, making the body produce more of its own insulin, or making the body more sensitive to the effects of insulin. All of these approaches work directly on the insulin target tissues (liver, muscle, fat) and are critical parts of diabetes treatment. However, because the brain also helps control blood sugar, medications that target brain systems as opposed to insulin target tissues could be a useful new approach to managing diabetes. We have found that the brain becomes impaired in obesity in a way that may affect body weight and blood sugar balance. This project explores the possibility that glial cells (the brain's damage response cells) in the hypothalamus area of the brain play an important part in the process of becoming obese and developing diabetes. We are using a wide variety of techniques to study and manipulate glial cells in order to determine the extent of their contribution to weight and blood sugar regulation and whether they can be engineered to help reverse obesity and diabetes.
Wolfgang Peti, PhD
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University of Arizona College of Medicine, Tucson, AZ
Novel, innovative insights into insulin signaling and regulation using NMR spectroscopy
The prevalence of diabetes in the US is now at epidemic levels. In order to develop new drugs that not only improve treatment, but eventually provide a cure, requires a full understanding of the signaling pathways in the body that drive this disease. The aim of this project is to apply state-of-the-art molecular approaches to study the protein enzymes that regulate insulin signaling and glycogen metabolism. This project uses nuclear magnetic resonance (NMR) spectroscopy, the high-resolution cousin of magnetic resonance imaging (MRI), to study these proteins. This cutting edge technique will provide insight into how these enzymes function—down to the atomic level. More importantly, it will enable the investigation of how the intrinsic functions of these enzymes can be used to design novel, more potent drugs to fight diabetes.