2017 Grant Recipients
Jonathan N. Flak, PhD
University of Michigan, Ann Arbor, MI
Targeting the VMN to Understand Hypoglycemia Pathogenesis
Diabetes therapies often lead to 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 us to low blood glucose levels. This condition is called “hypoglycemia-associated autonomic failure” (HAAF), and it 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 reveal previously unknown mechanisms that contribute to hyperglycemia in diabetes.
Aleksander David Kostic, PhD
Joslin Diabetes Center, Boston, MA
Generation of an in vivo system for dissection of the human type 1 diabetes-associated microbiome
The bacteria that inhabit the human intestinal tract may be a critical contributor to the rise in T1D incidence. This study will explore whether gut microbes produce a stimulus that causes islet autoimmunity. The study aims to identify particular microbiome species, genes, and metabolites that impact the immune system and metabolism in such a way that either promotes or prevents T1D. Targeting the mechanisms by which the microbiome impacts disease therapeutically represents a new pathway to prevent type 1 diabetes..
Paul Cohen, MD, PhD
The Rockefeller University, New York, NY
Dissecting the role of beige fat in metabolic homeostasis
Not all fat cells are the same. White fat stores excess energy. In the obese state, white fat cells become inflamed and contribute to diabetes. Brown fat dissipates energy and protects against obesity and diabetes. Beige fat cells are brown-like cells present within white fat. This study will test whether a factor 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, NY
Central nervous system regulation of glucose metabolism
The brain is a crucial part of the complex system that responds to and regulates blood glucose levels. Defects in these responses limit therapy in type 1 diabetes and may contribute to type 2 diabetes. This study examines a region of the brain called the amygdala, which may contribute to glucose regulation. This proposal will use novel techniques to investigate the contribution of a specific population of glucose-sensing neurons in the amygdala to glucose metabolism and diabetes. With this foundation, future studies may explore whether restoring glucose responses in these neurons or manipulating downstream pathways 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. Despite enormous effort, few continuous glucose monitors have achieved FDA approval to date. This project aims to apply novel engineering approaches to develop a minimally invasive, disposable continuous glucose monitoring patch that uses microneedles to directly sample the blood at five-minute intervals. A key asset to the planned approach is that it will employ FDA approved materials, reducing the regulatory hurdle to move the patch to market, if successful.
David A. Spiegel, PhD
Yale University School of Medicine, New Haven, CT
Targeting Glucosepane Crosslinks in Diabetes
Glucosepane is a molecule derived from glucose. Because glucose levels are high in people with diabetes, glucosepane levels are 20 times higher in people with diabetes than those without. Evidence suggests that glucosepane contributes to the development of diabetes. High glucosepane is also an independent risk factor for the onset of 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. Insights from these studies will guide our approach towards developing a therapeutic agent that may ultimately reverse diabetes-associated tissue damage.