Research Description
Type 2 diabetes (T2D) associates with a decrease in important brain matrix structures that surround and protect neurons involved in energy and glucose regulation. In addition to the loss of the abundance of these important matrix structures in the hypothalamus of T2D rodents, patients with obesity also exhibit changes in the chemical composition of these brain matrices that are predicted to decrease hormones and nutrient interactions with neurons the brain. This ADA Innovative Basic Science proposal aligns with the goals of Precision Medicine to better understand the pathophysiology of brain matrix changes in states of obesity and diabetes, spanning both rodents and humans. As such, studies described within this proposal will provide critical knowledge on how hypothalamic matrices surrounding key metabolite-sensing neurons change throughout the progression of metabolic diseases and across species. Although it is predicted that obesity may influence metabolic signaling by altering the integrity of these brain matrices, these changes may be exacerbated in T2D. By understanding how PNN abundance and composition changes over the course of obesity and T2D, and how these changes relate to functional signaling of hormones and nutrients in the hypothalamus, new knowledge will be gained for future clinical drug development targeting matrix stabilization for the prevention and reversal these metabolic disorders at specific clinical bench marks in the disease progression.Research Profile
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?My obesity and diabetes precision medicine research project proposes to investigate novel mechanisms mediating the brain’s control of energy homeostasis and blood glucose in pre-clinical rodent models of energy dysregulation, and moreover, translate these findings to humans. The focus of my project aims to understand how the extracellular matrix surrounding energy-sensing neurons in the mediobasal hypothalamus can influence the activity and/or signal transduction of the underlying neurocircuits. I foresee this project providing critical insights into how changes in extracellular matrix pathology influence activity of neurons in the brain, and thus influence their function in regulating body fat mass and glycemia, which will provide novel targets for both the prevention and the treatment of obesity and diabetes.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?Brain cells in the hypothalamus sense fat abundance and blood glucose and communicate with other metabolic organs to regulate energy homeostasis. However, little is known regarding the function of the extracellular matrices that enmesh these critical neurocircuits. My research has identified defects in the extracellular matrices surrounding energy-sensing neurons in the hypothalamus of pre-clinical rodent models of obesity and diabetes, and furthermore, my preliminary evidence suggests that these defects are translatable to patients with obesity and diabetes. Therefore, by continuing to investigate such innovative and relevant precision medician-focused research, I will help those with obesity and diabetes by targeting their extracellular matrices surrounding energy-sensing neurons to better improve the regulation of body fat mass and blood glucose homeostasis in obesity and diabetes.
Why important for you, personally, to become involved in diabetes research? What role will this award play?My immediate family has an extensive history of obesity, pre-diabetes and diabetes that provides a personal perspective to my obesity and diabetes research. I am honored that my research will help identify novel targets and develop new obesity and diabetic therapies for such a complex and multifaceted disease. I find fulfillment in my research knowing that my findings might directly benefit the health of my family and many others around the world.
In what direction do you see the future of diabetes research going?As more sophisticated technologies emerge, I foresee the future of patient care shifting to focus on precision medicine research that elucidates the role of the brain in the control of energy and blood glucose homeostasis. There is an unmet need to further understand how both energy- and glucose-sensing neurons are impacted by changes in their surrounding matrix extracellular environment in the control of peripheral body fat storage and blood glucose. Furthermore, the potential for neurocircuit remodeling as a therapy to treat metabolic disorders is an innovative and cutting-edge area of neuroscience research in all biomedical fields, and the application to diabetes therapy has breakthrough translational potential on present-day treatments.