2017 Grant Recipients
Jonathan N. Flak, PhD
University of Michigan, Ann Arbor, Mich.
Targeting the VMN to Understand Hypoglycemia Pathogenesis
Diabetes therapies often lead to the risk of hypoglycemia—blood glucose levels that are too low. Hypoglycemia is especially dangerous in individuals who lack the normal nervous system response that alerts them to low blood glucose levels. This condition, which is called “hypoglycemia-associated autonomic failure” (HAAF), causes more frequent and more severe hypoglycemic episodes. This study will explore the role of the brain in development of HAAF. The results will identify potential treatment or prevention targets for HAAF and may also reveal previously unknown mechanisms that regulate glycemic control in diabetes.
Aleksandar David Kostic, PhD
Joslin Diabetes Center, Boston
Generation of an in vivo System for Dissection of the Human Type 1 Diabetes-associated Microbiome
The bacteria that inhabit the intestinal tract may contribute to development of T1D. This project will explore whether gut microbes produce a stimulus that causes islet autoimmunity. The study aims to identify particular microbe species, genes, and metabolites that impact the immune system and metabolism in such a way that either promotes or prevents T1D. Specific species associated withT1D will be identified and introduced into animal models to induce autoimmune diabetes. Then the investigators will directly target the microbiota therapeutically in a way that could be translatable to human disease. Targeting the mechanisms by which these microbes impact disease offers a potential new, widely accessible public health approach to preventing T1D.
Paul Cohen, MD, PhD
The Rockefeller University, New York
Dissecting the Role of Beige Fat in Metabolic Homeostasis
Not all fat cells are the same. Most of the fat tissue in the body is composed of white fat cells that are primarily used for storage of excess energy. In the obese state, white fat cells become inflamed and contribute to diabetes. In contrast, brown fat cells dissipate energy as heat and protect against obesity and diabetes. Beige fat cells are present within white fat. They share many properties with brown fat, and, as a result, are an interesting target for modulating metabolism. This study will test whether factors present in beige fat can reduce glucose production by the liver, thereby lowering blood glucose levels. The results could facilitate the development of novel mechanism-based therapies to treat diabetes and other obesity-associated diseases.
Sarah A. Stanley, MD, PhD
Icahn School of Medicine at Mount Sinai, New York
Central Nervous System Regulation of Glucose Metabolism
The brain is a crucial part of the complex system that regulates blood glucose levels. Defects in these responses limit therapy in T1D and may contribute to T2D. This study examines regions of the brain that may link hormone responses and emotion. These areas may contribute to glucose regulation through circuits linked to the pancreas. The investigators will use novel techniques to determine the contribution of a specific population of glucose-sensing neurons to glucose metabolism and diabetes. With this foundation, future studies will explore whether restoring glucose responses in these neurons can prevent or reverse diabetes and its complications.
Sumita Pennathur, PhD
University of California, Santa Barbara
Untethering Diabetes through Innovative Engineering
Achievement of good glucose control in people with diabetes depends on frequent self-monitoring of blood glucose values and appropriate adjustment and administration of therapeutics. Current developments in continuous glucose monitoring (CGM) strive to provide more precise readings with convenient and pain free devices. This project aims to apply novel engineering approaches to develop a painless, minimally invasive, accurate and disposable CGM patch. Advances like these will be critical for bringing the benefits of CGM to more people with diabetes.
David A. Spiegel, MD, PhD
Yale University School of Medicine, New Haven, Conn.
Targeting Glucosepane Crosslinks in Diabetes
Glucosepane is a product in cells that results from interactions between proteins and glucose. It occurs naturally in many cellular proteins. Because glucose levels are high in people with diabetes, glucosepane levels are 20 times higher in people with diabetes than those without. High glucosepane is an independent risk factor for the onset of complications of diabetes, including nephropathy, retinopathy, and neuropathy. This project aims to determine the extent of glucosepane modifications in tissues throughout the body, the effects of these modifications, and mechanisms by which glucosepane formation can be altered. The idea is that preventing or reversing glucosepane formation may have the potential to undo diabetes-associated tissue damage.