Eric E. Kelly, Ph.D., Associate Professor, Department of Physiology and Pharmacology
Graduate program affiliation: Cellular and Integrative Physiology
PhD: University of Iowa, Free Radical Biology
Postdoctoral Training: UAB, Center for Free Radical Biology
Office: 3074 Health Science Center North
- Redox- and ●NO-mediated signaling in vascular dysfunction and cancer.
- Interplay between ROS, ●NO and uric acid in metabolic and cardiovascular dysfunction allied to obesity.
- Manipulating oxidant and ●NO generation in cerebral vessels following ischemic stroke.
- Oxidant signaling in aging.
- Xanthine oxidase in hemolytic disease (e.g. sepsis, sickle cell, malaria, cardiac bypass etc.)
The overarching theme of the Kelley lab orbits around the convergence of inflammation with enhanced rates of oxidant generation; both of which are hallmarks of metabolic syndrome and diabetes yet, are allied to a plethora of disease processes including cancer. A current and specific focus of our efforts involves manipulating the enzymatic activity of xanthine oxidase (XO), a critical source of reactive species and uric acid in obesity/diabetes. Capitalizing on the recent discovery that XO can also catalyze the reduction of nitrate (NO3-) and nitrite (NO2-) to salutary ●NO, we have recently observed that elevation of circulating levels of NO2- /NO3- in obese mice results in beneficial outcomes including reduction in oxidative stress, blood glucose and improved cardiopulmonary function. With obesity/diabetes being epidemic in the U.S. there is a pressing need to intervene by addressing the root causes. This being said, there is an exploding population of obese/diabetic patients presently in need of treatment for related cardiovascular disease. By focusing on XO, our findings are rapidly translatable to the clinic via off-label application of FDA-approved XO inhibitors and/or sources of NO3- /NO2-.
A second recently-funded aim of our lab is to examine XO as a target for ischemic stroke in the context of obesity. By applying the lessons learned with our obesity/metabolic studies, we hope to produce a treatment approach that will augment the current clinical strategy and/or extend the narrow and limited treatment window provided by TPA.
Our third major aim is to identify critical redox-mediated contributors to aging. This project is a collaborative effort with the Scripps Institute where we are exploring the Free Radical Theory of Aging using a murine model of human progeria. Our goal is to define the interplay between diminished antioxidant capacity, elevated mitochondrial ROS generation and enhanced activity of enzymatic sources of oxidants that are correlative with both normal and accelerated aging.
A fourth aim focuses on identifying XO as a drug target for hemolytic disease. Our recent findings demonstrate a robust elevation in plasma XO during hemolytic crisis. We are collaborating with partners at Pitt and LSU, Shreveport to develop a novel small molecule compound that inhibits XO from binding to the vascular endothelium and thus alleviate vascular dysfunction.
While these current aims represent a wide range of techniques, our primary strength is redox biology and thus we actively collaborate with experts in various fields including cardiology and oncology to amplify our research prowess while ensuring success.