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.