Current Funding Awardees
Pilot and Feasibility Awardees
Mauricio Dorfman, Ph.D.
Research Assistant Professor
Department of Medicine
Obesity is a global epidemic that is the leading risk factor for the development of adverse metabolic comorbidities including type 2 diabetes. Reduction of testosterone levels in men increases the risk of obesity and type 2 diabetes, which is reversed by testosterone administration. Despite increasing evidence in both clinical and epidemiological studies in humans, the mechanism by which a decline of testosterone contributes to increased adiposity remains largely unclear. Obesity is associated with activation of inflammatory cells called microglia in the hypothalamus, a brain region that controls appetite and metabolism. Since recent studies have demonstrated that reducing hypothalamic microglial inflammation prevents diet-induced obesity, and testosterone supports metabolic and immunological health in males, we hypothesized that the mechanism by which testosterone protects from metabolic disease involve a reduction of hypothalamic microglial inflammation induced by high-fat diet.
Oleg Zaslavsky, Ph.D., M.H.A., R.N.
Department of Biobehavioral Nursing
and Health Informatics
In the U.S. persons over the age of 80 years, or octogenarians, are now the fastest growing portion of the total population. Along with this continuous rise, there is a significant burden of diabetes in this population. We propose to examine the relationship between glucose levels and rates of physical and cognitive decline in the octogenarians with diabetes participating in a large cohort of the NIA-funded Adult Changes in Thought (ACT) study, a community-based long-term prospective study of aging. The proposed study provides an extraordinary opportunity to develop new insights into the longitudinal association between glucose levels and functional health in the very old with diabetes. Findings from the proposed study will advance our understanding of the role of glycemic control on cognitive and functional ability in an understudied aged population and will provide preliminary data for developing strategies to mitigate the adverse effects of over or under treatment.
Dick and Julia McAbee Fellowship Awardee
Meghan F. Hogan, Ph.D.
(Mentor: Steven E. Kahn, M.B., Ch.B.)
Postdoctoral Research Fellow
Department of Medicine
Islet amyloid occurs in the majority of patients with type 2 diabetes, contributing to decreased β-cell mass and impaired insulin release. However, mechanisms underlying islet amyloid’s cytotoxicity remain poorly understood. Under conditions of amyloid deposition in the islet, we have found that Steroidogenic Acute Regulatory protein (StAR) is highly upregulated. In a number of tissues StAR transports cholesterol across the mitochondrial membrane, where it is classically processed by CYP family members. The resultant molecules include some that protect against tissue damage. However, StAR’s role in the islet is unknown. We have also shown that (a) StAR is present in β cells, (b) its levels increase with amyloid formation and this is accompanied by an increase in cellular cholesterol, and (c) islets lack many of the CYPs that typically metabolize cholesterol, preventing its diversion into protective roles in the islet. Exploring StAR and related cholesterol metabolism in the amyloid-laden islet should provide promising strategies for preventing β-cell loss, which may lead to additional therapeutic approaches for type 2 diabetes.
Samuel and Althea Stroum Fellowship Awardee
(Mentor: Judit Villen, Ph.D.)
MCB Graduate Student
Department of Genome Sciences
Activated brown fat rapidly burns calories to generate heat. Individuals with type-2 diabetes, and other metabolic disorders, would likely benefit from therapies that increase brown fat activity. Cold stress, high-fat feeding, and tissue-specific knockout of the kinase mTORC2 all activate brown fat, yet themselves are not practical therapies. To gain a detailed molecular understanding of brown fat activation, I will compare proteomic signatures associated with different modes of activation by measuring global levels of proteins and their post-translational modifications. I ultimately aim to discover molecular determinants of brown fat activity that could be exploited for therapeutic benefit.