Local Research

Top 5 things to know about the Association's Research:

  1. We have the most comprehensive diabetes research grants program in the country.
  2. Over the years, the Association has invested more than $550 million in diabetes research and provided funding for more than 4,000 research projects.
  3. 100 percent of all allocated gifts to support diabetes research are used only to support research.
  4. For all donations $50,000 or above, donors can select the specific research project that they would like to fund.
  5. According to the 2002-2007 Research Program Assessment, 97 percent of researchers supported by the Association continued their careers in diabetes research.

To learn about the Association's nationally funded research, visit www.diabetes.org/research-and-practice/. For more information or to make a donation towards our research efforts, please contact Kevin Kelly at kkelly@diabetes.org.   

Meet Our Locally Funded Researchers

Klaus H. Kaestner, PhD (University of Pennsylvania)
Functional analysis of the diabetes gene Hhex in endocrine pancreas development and physiology
General Research Subject: Both type 1 and type 2 diabetes
Focus: Genetics \ Type 2 Diabetes

The goal of this project is to investigate whether Hhex is essential for the differentiation of endocrine islets and glycemic control in adulthood. Multiple genetic mouse models and shRNA will be employed to inactivate Hhex in endocrine progenitor cells and adult endocrine cells in mice and in human primary islets, respectively. Results from this project will position Hhex in the transcriptional network governing pancreas development, and assess its potential as a driver for stem cell differentiation towards fully functional islets for implantation. Furthermore, the studies on adult function of Hhex in glucose homeostasis will determine if and by what mechanism Hhex contributes to the pathogenesis of diabetes.

Diana E. Stanescu, MD (Children's Hospital of Philadelphia)
The maturation of beta cells in human development
General Research Subject: Both type 1 and type 2 diabetes
Focus: Islet Biology \ Beta Cell Growth and Differentiation

This study proposes that, in vitro stem cells do not fully mature. The goal is to look at how fetal beta cell function through the first and second trimester of pregnancy, in order to understand what leads to insulin secretion at different ages. Secondly, the author is going to study the genetic information (mRNA) of individual fetal beta cells, and see what changes from one age to another. These findings will be compared to beta cells generated in vitro and to adult beta cells. Understanding how fetal beta cells mature in the human pancreas will provide a blueprint on how to optimize the growth and maturation of stem cells in vitro, in order to lead to fully functioning beta cells, that could be further used to cure diabetes.

Kathryn Wellen, PhD (University of Pennsylvania)
Title: Metabolic regulation of histone acetylation in adipocytes
General Research Subject: Type 2 diabetes
Focus: Adipocytes

The research will investigate whether histones near genes of interest are specifically regulated in a nutrient-responsive manner.  Additionally, it is known that additional proteins call acetyltransferases are necessary to mediate the effects of ACL on histone acetylation, and the identity of these proteins will be investigated in order to define a clear mechanism through which ACL regulates histone acetylation.  Finally, the proposed work will investigate how insulin-regulated signaling pathways control the activity of ACL and its ability to modulate histone acetylation levels and gene expression in adipocytes.  These studies should provide novel insight into mechanisms underlying metabolic diseases and could potentially suggest novel therapeutic targets.

Jim Song, PhD (The Pennsylvania State University Milton S. Hershey Medical Center)
Stem cell-derived regulatory T cells for theraupeutic use of autoimmune diabetes
General Research Subject: Type 1 diabetes
Focus: Immunology

Pluripotent stem cells (PSC) provide a chance to obtain a renewable source of healthy regulatory T cells (Tregs) to treat a wide array of autoimmune disorders; however, the right circumstance for development of Tregs from PSC (i.e., PSC-Tregs) remains unknown. The project will determine the mechanisms behind immunotherapies of Ag-specific PSC-Tregs, aiming to modulate immune tolerance for autoimmune disorders. The knowledge gained from these studies will provide new insight and strategies into cell-based therapies of autoimmune disorders such as type-1 diabetes, and advance the understanding of fundamental mechanisms underlying Treg cell differentiation.

Rexford Ahima, MD, PhD (University of Pennsylvania)
Role of IPMK in metformin-mediated metabolism
General Research Subject: Type 2 diabetes
Focus: Integrated Physiology \ Insulin Resistance

The studies show that an enzyme, inositol polyphosphate multikinase (IPMK), is involved in glucose sensing in cells. Importantly, IPMK activity in liver is associated with the action of metformin, one of the most popular drugs for treatment of type 2 diabetes. Metformin enhances insulin action in liver and decreases blood glucose; however, the underlying mechanisms are unclear. To elucidate the action of IPMK, it is going to specifically disrupt the enzyme in liver and examine how this affects glucose and lipid metabolism in mice fed a high-fat (Western diet). The study will also investigate whether IPMK plays a critical role in the molecular actions of metformin. These studies will increase the knowledge of cellular metabolism, and lead to the development of new drugs for diabetes.

Michael D. Dennis, PhD (The Pennsylvania State University Milton S. Hershey Medical Center)
Hyperglycemia-induced translational control of gene expression in the retina
General Research Subject: Both type 1 and type 2 diabetes
Focus: Complications \ Ocular

The overall goal of this research is to identify new targets for intervention at the molecular level that will lead to development of innovative, nondestructive therapies that target the etiology of diabetic retinopathy. The pathogenesis of this disease is caused by a combination of hyperglycemia and a reduction in insulin mediated signaling, which results in neurovascular complications through the induction of structural and physiological changes in the retina.

The research is innovative, because it represents an entirely different approach to address the molecular basis of diabetic retinopathy. The central hypothesis is that the covalent addition of O-linked N-Acetylglucosamine (O-GlcNAcylation) to serine or threonine residues of translation initiation factors mediates a shift from cap-dependent to cap-independent mRNA translation, resulting in an altered gene expression pattern that contributes to the pathophysiology of diabetic retinopathy. With respect to specific outcomes, this research is expected to characterize a novel mechanism that links the metabolic abnormalities associated with diabetes to enhanced vascular growth factor expression in the retina. The rationale is that once the mechanisms underlying altered gene expression in the retina are known, the function/assembly of translation initiation factors can be manipulated pharmacologically, resulting in therapies that address the prevention and treatment of neurovascular complications that produce 24,000 new cases of diabetes related vision loss each year.

Shogo Wada, PhD (University of Pennsylvania)
Novel mechanism of adipose tissue browning
General Research Subject: Obesity
Focus: Adipocytes

Obesity is a major risk factor for development of diabetes. White adipose tissue (WAT) stores excess calories as fats. WAT primarily stores fat under basal conditions but is capable of burning fat under conditions of cold exposure. This metabolic conversion is called "browning", which is named after brown adipose tissue (BAT) where fats are more actively catabolized. Adipose tissue browning is known to be beneficial for obesity prevention and therefore elucidation of the underlying mechanism is of great importance. One of most significant difference between WAT and BAT is amount of mitochondria, a powerhouse of cells. BAT is richer in mitochondria than WAT because mitochondria in BAT burn fat as a substrate of oxidative respiration. It is also known mitochondrial content dramatically increases in WAT upon browning. FLCN, a tumor suppressor of kidney cancer, is known to inhibit mitochondrial biogenesis in several tissues other than adipose tissue. Based on this notion it was hypothesized FLCN deficiency in fat makes it brown by increasing mitochondria. As expected having no FLCN leads to adipose tissue browning. Furthermore preliminary data have shown FLCN hierarchically inhibits TFE3 activity, a molecule that directly controls gene expression of mitochondria.

This study aims at analyzing molecular mechanism underlying TFE3 inhibition by FLCN and characterization of glucose metabolism and obesity resistance of FLCN deficient animals. By the completion of this study the molecular targets downstream of FLCN will be elucidated, which may provide putative drug targets for obesity prevention and diabetes treatment.

Patrick Seale, PhD (University of Pennsylvania)
Age-dependent regulation of beige fat precursor activity
General Research Subject: obesity
Focus: Adipocytes

Obesity and type 2 diabetes are leading causes of preventable death in the U.S. A promising approach to treat these diseases is through enhancing the activity of beige fat cells. Beige fat cells develop in white fat tissue where they function to expend chemical energy (from sugar and fats) in the form of heat. This energy burning capacity of beige fat cells promotes weight loss and can reverse metabolic disease. However, we still know very little about how beige fat cells develop which limits our ability to target this cell type for therapies. We recently developed novel genetic approaches that allow us to track and study beige fat cell development in mice. Interestingly, we also found that beige fat development is severely impaired in middle aged and old mice relative to young animals. Moreover, aging leads to pathological fibrosis (the accumulation of fibrous connective tissue) in fat tissue which contributes to dysfunction. We hypothesize that the same cells that develop into beige fat cells in young mice are the source of fibrosis-promoting cells in older animals. We will test this idea by analyzing the fate of beige fat precursor cells in young and old mice. We will also examine the molecular mechanisms that may be responsible for controlling this cell fate switch. By studying the natural mechanisms that control beige and brown fat development we will uncover novel avenues to reduce metabolic disease.

Yajing Wang, MD, PhD (Thomas Jefferson University)
Adiponectin Malfunction and Diabetic Vascular Injury
General Research Subject: Type 2 diabetes
Focus: Complications \ Macrovascular-Cellular Mechanisms of Atherogenesis in Diabetes

The study will test a novel hypothesis that the AdipoR1/Cav1/APPL1 "signalsome" is essential for APN vascular protection, and disassembly of this signalsome causes endothelial APN resistance, which contributes to diabetic vascular injury. The molecular mechanisms responsible for signalsome "assembly" under normal conditions will first be clarified, and then the molecular modifications leading to APN signalsome "disassembly" under disease conditions will be investigated. Completing these experiments will 1) overcome obstacles barring complete understanding of APN signaling; 2) identify molecular mechanisms leading to APN resistance during obesity/diabetes; and 3) identify novel vasculoprotective targets in diabetic patients.

Xin-Liang Ma, MD, PhD (Thomas Jefferson University)
Identification of CTRP9 as a Novel Cardioprotective Cardiokine and its Inhibition by Diabetes
General Research Subject: Type 2 diabetes
Focus: Complications \ Macrovascular-Atherosclerotic CVD and Human Diabetes

The study will identify the specific cell type(s) responsible for producing cardiac CTRP9, altered by diabetes (Specific Aim 1). It will employ unique tools to define the detailed molecular mechanisms responsible for CTRP9 processing (Specific Aim 2). Finally, It will identify and clarify the proteins activated by CTRP9, responsible for its protective effects against heart attack injury. Successful completion of this application will not only reveal how CTRP9 regulates heart function, but also advance the search in discovering the best strategy ultimately reducing heart injury in diabetic patients.

  • Last Reviewed: March 2, 2015
  • Last Edited: November 28, 2016