2019 Grant Recipients
Ebony Boyce Carter, MD
Washington University, St. Louis, MO
Targeted lifestyle change group prenatal care for obese women at high risk for gestational diabetes: a randomized controlled trial
Medical complications that develop during pregnancy, such as gestational diabetes, can affect the long-term health of mothers and their children. While most women with gestational diabetes return to normal immediately after delivering their babies, they remain at significantly higher risk of developing type 2 diabetes in the years immediately following pregnancy. Dr. Carter has designed an innovative and practical intervention, called Targeted Lifestyle Change Group Prenatal Care (TLC), that can be integrated in routine prenatal care. She will compare this approach to traditional prenatal care in a community of women who are predominantly low-income, African American, have high levels of obesity, and are at high-risk for developing gestational diabetes, to determine whether it improves health outcomes for both women and their children. If successful, this effort has the potential to mitigate the transgenerational risk for type 2 diabetes in high-risk populations.
Matthew J. Webber, PhD
University of Notre Dame, Notre Dame, IN
Hypoglycemic rescue with glucose-responsive glucagon delivery devices
Low blood sugar levels are a serious threat to people with diabetes—especially during sleep, when they are less aware of the condition and less able to safely counteract it by ingesting glucose. This danger leads to sleepless nights for patients and their caregivers. Using his background in materials science, Dr. Webber has outlined an innovative approach to proactively prevent the threat of low blood sugar. His idea centers around the development of materials that can both sense glucose levels and respond to low glucose by automatically releasing the hormone glucagon. This approach will be automated and integrated into patient-friendly delivery devices, offering promise to provide a safe and care-free way to prevent potentially lethal glucose lows while mitigating a serious physical and psychological burden for people with diabetes.
Sarah A. Tishkoff, PhD
University of Pennsylvania, Philadelphia, PA
Genetic risk factors for adult-onset diabetes in populations of African Ancestry
Populations of African descent, including African-Americans, have high rates of type 2 diabetes, but we don’t yet understand exactly why. Dr. Sarah Tishkoff will use her expertise in the genetics of Africans to unravel the mysteries underlying this health disparity. She has identified three separate ethnically diverse African populations living indigenous lifestyles with widely different rates of diabetes. Through analyzing the differences in their DNA, immune systems and metabolism, Dr. Tishkoff seeks to understand why some indigenous populations are protected from diabetes, while others are at high risk. Understanding the risk factors for diabetes in populations of African ancestry is critical for developing better, more precise diagnostics and therapeutics and eliminating disparities in diabetes.
2018 Grant Recipients
John Nelson Campbell, PhD
Beth Israel Deaconess Medical Center, Boston, MA
Molecular and functional taxonomy of vagal motor neurons
We know that the brain relays information about the environment to organs throughout the body to coordinate their functions. A specific set of neurons, known as vagal motor neurons, is known to control digestion, insulin release, and glucose production from the liver, but scientists don't yet understand precisely how they work. Dr. Campbell is profiling gene expression in vagal motor neurons to identify genetically-distinct subtypes, and then matching each subtype to its specific role in organ function. These studies will yield unprecedented insight into how the brain controls digestion and glucose metabolism and identify potential new therapeutic targets for diabetes.
Maureen Monaghan, PhD
Children's Research Institute, Children's National Health System, Washington, DC
Improving Health Communication During the Transition from Pediatric to Adult Diabetes Care
Adolescents and young adults (ages 17-21) with type 1 diabetes are at high risk for negative health outcomes, including poor glycemic control and disengagement from the health care system. The period of transition from pediatric to adult diabetes care represents a particularly risky time. Dr. Monaghan aims to leverage innovative technologies to improve youth communication skills and behaviors related to planning for diabetes visits, disclosing diabetes-related concerns, and optimizing glucose data review in preparation for entrance into adult diabetes care. This intervention has the potential to improve diabetes self-care skills. Equipping adolescents and young adults with skills to enhance health communication may hasten the development of key self-advocacy skills needed for successful engagement in adult diabetes care and, thus, establish a lasting pattern of positive health behaviors.
Alexander R. Nectow, PhD
Princeton University, Princeton, NJ
Investigation of Brainstem Neurons Regulating Energy Balance
Energy balance is tightly regulated by the brain, which detects changes in nutritional state and in turn modulates food intake, energy expenditure, and metabolic function. This sense-and-respond system is comprised of neurons throughout the brain, particularly within the hypothalamus and brainstem. However, the mechanisms through which dysfunction of this system leads to obesity and diabetes are unknown. Dr. Nectow will explore the function of recently characterized inhibitory neurons in the brainstem, and ask whether these neurons are capable of regulating metabolism in healthy and obese mice. The results from this project may lead to a better understanding of the brain's dysregulation in obesity and diabetes, and could thus have direct implications for the prevention and treatment of these debilitating disorders.
Michael L. Stitzel, PhD
The Jackson Laboratory, Farmington, CT
Deciphering Longitudinal Cell Type-Specific Defects in Diabetes Pathogenesis
The pancreas features cell clusters called islets that contain multiple cell types that perform distinct functions, including the insulin-producing beta cells. Understandably, much diabetes research focuses on the beta cell. However, other cell types within the islet are also disrupted in type 2 diabetes and these changes are associated with disease progression. Dr. Stitzel aims to identify cell-type-specific molecular signatures of islet dysfunction and type 2 diabetes using innovative genomic approaches. His project will profile gene expression in single islet cells to define the cell types and determine differences between islets from individuals with normal glucose, prediabetes, and type 2 diabetes. This work will reveal the fundamental molecular features governing the identity and function of each islet cell type and provide a roadmap of the cell-type-specific changes that accompany diabetes. The results may lead to the identification of novel targets to prevent and treat type 2 diabetes.
Samie R. Jaffrey, MD, PhD
Weill Cornell Medicine, New York, NY
Rewiring Cellular Metabolic Networks in Diabetes
Diabetes is associated with highly complex changes in cellular metabolism. Dr. Jaffrey sets out to develop a new type of gene therapy that will change gene expression in diabetes-affected cells and tissues. The approach involves expressing a new class of RNA molecules that function as molecular devices that perform corrective therapeutic actions, including sensing glucose and inducing insulin and GLP-1 production; inhibiting insulin resistance; and suppressing glucose production from the liver. The therapeutic devices will be tested in animal models of diabetes to provide critical proof-of-principle data needed to move toward human gene therapy trials to alleviate the burden of diabetes.
Jonathan V. Sweedler, PhD
University of Illinois, Urbana-Champaign, IL
Unraveling Diabetes Progression a Cell at a Time
Pancreatic islets play critical roles in both type 1 and type 2 diabetes. Subtypes of pancreatic beta cells are known to respond differently to chemical signals, and Dr. Sweedler seeks to understand how these cellular differences influence chemical signaling in diabetes. By understanding changes that occur during disease progression, we will gain insight into the chemical mechanisms surrounding beta cell destruction in type 1 diabetes, and insulin resistance and subsequent loss of beta cells in type 2 diabetes. The project will use advanced technologies to determine the differences between individual human islet cells affected by type 1 diabetes and by type 2 diabetes. The results will elucidate new chemical parameters characteristic of each disease, helping to identify novel therapeutic pathways that can be exploited for the prevention, treatment, and cure of diabetes.
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 sugar levels that are too low. Hypoglycemia is especially dangerous in individuals who lack the normal nervous system response that alerts us to low blood sugar 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 sugar 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 sugar 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 sugar 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.
2016 Grant Recipients
Sui Wang, PhD
Read about Dr. Wang's Accomplishments
Stanford University, Stanford, CA
Dissection of Gene Regulatory Networks Underlying Diabetic Retinopathy
Diabetes affects the retina, the inner layer of the eye responsible for communicating the images we see to the brain. Diabetic retinopathy is one of the most common complications of diabetes and is the leading cause of blindness among working-age adults. Currently, the only therapies for retinopathy are laser treatment and injection of drugs, which are used to slow down the progression of retinopathy, but are not able to reverse vision loss. To instead prevent diabetic retinopathy before it starts, researchers need to better understand how it develops in the first place. Dr. Wang is pursuing an innovative approach to understanding how diabetes impacts gene activity in the retina. She plans to map the gene networks involved in the initial development and progression of retinopathy. With this information, we can better identify early signs of retinopathy to begin treatment before vision loss occurs, and perhaps discover previously unknown molecules that may be candidates for the development of new drugs to preserve vision.
Phillip James White, PhD
Read about Dr. White's Accomplishments
Duke Molecular Physiology Institute, Duke University, Durham, NC
A New Homeostatic Mechanism for Metabolic Control
Very frequently, fatty liver and insulin resistance precede the onset of type 2 diabetes. Compounds called "branched chain amino acids" (BCAAs), which come from certain proteins in our diets, are linked to insulin resistance and risk for developing type 2 diabetes. However, precisely how circulating BCAAs are connected to abnormal glucose and lipid metabolism is unclear. Dr. White has discovered that some of the components of the molecular network that go awry in protein metabolism and prevent BCAAs from breaking down also interact with both glucose and lipid metabolism pathways in the liver. Dr. White's project will examine this network and how it is controlled. He hopes to further define how the molecules interact to control fat and glucose metabolism – and then to identify where new drug development efforts may be focused to treat prediabetes, fatty liver disease and type 2 diabetes.
Daniel J. Ceradini, MD, FACS
Read about Dr. Ceradini's Accomplishments
Wyss Department of Plastic Surgery, New York University Langone Medical Center, New York, NY
Therapeutically Targeting Keap1/Nrf2 Dysfunciton in Diabetes
Diabetes is the leading cause of non-healing wounds and lower extremity amputation in the U.S. Despite efforts to tightly control blood sugar in people with diabetes, poor wound healing persists as a common complication. Dr. Ceradini has discovered that high blood sugar levels associated with diabetes disrupt antioxidant networks important for tissue regeneration. His project seeks to determine whether restoring this critical antioxidant pathway to normal will reverse the impaired tissue regeneration caused by diabetes. Using innovative approaches and technologies, Dr. Ceradini will develop and test a novel therapy to restore the antioxidant protection program and determine whether it can overcome poor wound healing in diabetes.
Zachary A. Knight, PhD
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University of California, San Francisco
Reinvestigation of the Arcuate Feeding Circuit
Because the brain controls food intake, it is likely to be an important target for new therapeutics to reduce obesity. However, little is known about the specific site in the brain where environmental or dietary signals override the system that normally regulates feeding and weight maintenance. Dr. Knight's project will use new technologies to investigate the key neurons in the brain that control food intake. If successful, this project will identify the signals that are responsible for activating the sensation of hunger, determine how the neurons motivate food consumption, and clarify how obesity leads to dysregulation of these neurons. Understanding of these networks in the brain may lead to development of new therapies to treat or prevent obesity by stimulating or inhibiting the neurons responsible for hunger and feeding behavior.
Praveen Sethupathy, PhD
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Systems Approach to Defining Genetic Regulation of Intestinal Physiology and Gut Microbiota in Diet-Induced Obesity
In the human body, microorganisms outnumber human cells ten to one. These microorganisms, mostly bacteria, are influenced by both diet and genetic factors and are linked to metabolic disease. The gastrointestinal tract is home to a significant population of microorganisms and is the primary organ system responsible for absorbing nutrients from food. Obesity and diabetes are associated with changes in the microbial communities of the gut and with impaired intestinal function. Dr. Sethupathy's project seeks to identify the genetic factors that contribute the most to shaping the way our intestines respond to gut microorganisms under normal conditions and in diet-induced obesity and diabetes. These studies could lead to the identification of new therapeutic targets that may be leveraged to prevent or effectively treat obesity and diabetes.
Andrew Scharenberg, MD*
Read about Dr. Scharenberg's Accomplishments
Seattle Children's Hospital and Seattle Children's Research Institute, Seattle, WA
Regulatory T-Cell Stabilization via Gene Editing as Novel Therapy for Type 1 Diabetes
Development of type 1 diabetes is known to involve the immune system inappropriately attacking the body's own insulin-producing beta cells. Several lines of evidence suggest that dysfunction of a type of immune cell, known as a thymic regulatory T-cell (tTreg), leads to a breakdown of normal protection from the immune system in insulin-producing beta cells. When the tTreg cells fail, the immune system begins to attack and destroy the body's own beta cells, leading to type 1 diabetes. Dr. Scharenberg is applying an innovative approach that he developed for "editing" genes to try to tackle type 1 diabetes. Using this technology, his Pathway to Stop Diabetes project aims to edit genes in tTreg cells to preserve their function and protect the beta cells from autoimmune attack, potentially preventing or reversing type 1 diabetes.
* Dr. Scharenberg relinquished his Pathway award in 2017 to accept an opportunity to become Chief Scientific Officer at Casebia Therapeutics. He credits the Pathway Visionary Award with developing the scientific expertise he needed to translate cell and gene therapies to type 1 diabetes. He continues to aim to apply these novel approaches to the treatment of autoimmune diseases, including type 1 diabetes.
2015 Grant Recipients
Celine Emmanuelle Riera, PhD
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Cedars-Sinai Medical Center, Los Angeles, CA
Identification of Sensory Neural Circuits Controlling Metabolic Disorders
In order to adapt quickly to changes in environmental conditions and perception of internal senses (such as digestion, temperature, hunger, pain and blood pressure), mammals rely on a part of the brain called the hypothalamus to integrate a variety of signals into appropriate responses and meet energy demand. However, it is not well understood whether neurons involved in sensory perception have the ability to translate sensory information into metabolic responses through communication with the hypothalamus and other brain regions. By focusing on the critical senses of pain and smell, which play important roles in the perception of harmful conditions and nutrient availability, this project will identify components of the metabolic response that become disrupted in type 2 diabetes.
Through better understanding of these sensory systems, and how they impact metabolic activity, new therapies to treat type 2 diabetes may be identified.
Stephanie Stanford, PhD
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University of California, San Diego
PTPN22: Model Gene to Unravel the Interaction between Genetics and Environment in Type 1 Diabetes
A mutation in a gene called PTPN22 is one of the strongest known genetic risk factors for type 1 diabetes (T1D). Viral infections are important risk factors for development of T1D, and the PTPN22 gene may play a critical role in defense against viruses. This project will study whether the mutated PTPN22 gene predisposes individuals to T1D by decreasing the response to viral infections. The results from this study will elucidate the mechanism by which a genetic T1D risk factor combines with an environmental trigger to confer disease susceptibility. Importantly, if correct, this model suggests that protection from and/or aggressive treatment of viral infections could prevent T1D in people with this genetic risk factor, and will pave the way to preventative treatment strategies for individuals at high risk of developing T1D.
Thomas Delong, PhD
Read about Dr. Delong's Accomplishments
The University of Colorado Denver, Aurora, CO
The Role of Hybrid Insulin Peptides in the Development of Type 1 Diabetes
Type 1 diabetes (T1D) is an autoimmune disease that is mediated by the immune system's own T cells. Normally, T cells fight infection by mounting a response to foreign bodies, called antigens, when they are detected in the circulation. While the immune system has mechanisms to prevent T cells from recognizing self-antigens, in T1D those mechanisms fail and T cells inappropriately attack the body's own insulin-producing beta cells. In order to prevent or reverse the development of T1D it is therefore critical to understand why and how T cells are misguided. This project describes a modification to self-antigens that are recognized by T cells that trigger diabetes in a major animal model for T1D. The researchers hypothesize that the same modification is relevant in the development of human T1D. They will test this hypothesis using T cells that were isolated from the remaining islet tissue of deceased human T1D patients. Additionally, the researchers have identified a potential mechanism that leads to these antigen modifications. They will study the mechanism and test whether the formation of modified antigens can be chemically inhibited, thereby blocking destruction of insulin-producing beta cells and preventing type 1 diabetes.
Zhen Gu, PhD
Read about Dr. Gu's Accomplishments
North Carolina State University, Raleigh, NC and University of North Carolina at Chapel Hill
Bio-Inspired Synthetic Pathway for Closed-Loop Delivery of Insulin and Glucagon
A therapeutic system capable of automatically regulating insulin delivery in proportion to blood sugar levels is highly desirable for people with type 1 and advanced type 2 diabetes. Several synthetic glucose-responsive formulations for self-regulated delivery of insulin have been developed. However, there are numerous remaining challenges to crafting a biocompatible system that would be easy to administer, provide a sufficiently fast insulin response, and prevent hypoglycemia. Inspired by the natural insulin vesicles in pancreatic beta cells, this project will develop artificial "synthetic insulin vesicles". The hypothesis is that the materials will be able to regulate release of insulin at high blood sugar levels and inhibit its release within the normal glucose range. To prevent potential hypoglycemia, the project includes design of "synthetic glucagon vesicles" to counteract unexpected large releases of insulin. If successful, these systems can fundamentally change how type 1 diabetes is managed and reduce the burden of monitoring and treatment.
Marie-France Hivert, MD
Read about Dr. Hivert's Accomplishments
Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, MA
Understanding Pathways of Fetal Metabolic Programming to Stop the Transgenerational Risk of Diabetes
Exposure to maternal hyperglycemia in the womb is associated with significantly higher lifetime risk of type 2 diabetes (T2D). The exact mechanisms explaining this phenomenon are still unknown. This project will apply recent technological advances to examine differences in how epigenetic regulation (one of the mechanisms that controls gene expression) is linked to in utero exposure to diabetes. By following mother-child pairs throughout pregnancy and childhood, the study is expected to identify new information about which epigenetic adaptations across the human genome are implicated in linking maternal blood sugar to the offspring's future T2D risk. Revealing new information about how T2D is triggered in these children could aid development of early life prevention measures to reduce rates of diabetes in future generations.
Mayland Chang, PhD
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University of Notre Dame, South Bend, IN
A Strategy to Accelerate Diabetic Wound Repair
A serious complication of diabetes is the inability of wounds to heal, which contributed to 73,000 lower-limb amputations in the United States in 2010. Currently, no therapeutic agents for the treatment of diabetic wounds are approved and there is a paucity of research to understand why diabetic wounds are difficult to heal. Preliminary work has identified enzymes called "matrix metalloproteinases" (MMPs) that seem to influence wound healing in diabetic mice. In addition, a drug has been identified that selectively blocks the detrimental MMP, is not toxic to mice, and is poised for development as a topical therapy for diabetic wound healing. This project proposes to validate the beneficial and detrimental roles of MMPs in human samples and to understand how MMP inhibitor drugs may improve diabetic wound healing. The combination of studies applying selective MMP inhibitors and using samples from people with diabetes is expected to lead to a new treatment for this serious complication of diabetes.
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.