Medicinal Chemistry

Marsha P Cole

Marsha P Cole
Dept of Biochemistry and Molecular Biology
University of Louisville, USA

Biography

Marsha Cole obtained her Bachelor’s and Master’s in Chemistry and PhD in Nutritional Sciences at the University of Kentucky in Lexington. Dr. Cole completed a postdoctoral fellowship at the University of Alabama Birmingham and was a Hartwell Fellow supported by The Hartwell Foundation at the University of Pittsburgh. In January 2009 she joined the Department of Pharmacology Chemical Biology at the University of Pittsburgh as an instructor and was promoted to Research Assistant Professor in 2010. Dr Cole’s research is funded by the National Institute of Health and her findings have become important scientific contributions leading to more than 25 publications in high impact journals such as Circulation Research and Journal of Biological Chemistry.

 

Research Interest

Dr. Coles research focuses on the endogenous generation of nitrated fatty acids (NO2-FA) in metabolic diseases, such as diabetes. Hyperglycemic and hyperlipidemic conditions support the presence of a pro-oxidative milieu in type II diabetes which can lead to increased mitochondrial production of reactive oxygen species and nitric oxide synthase activity. In particular, NO2-FA are generated in heart mitochondria through •NO-dependent oxidation and nitration and can mediate reactions that may beneficially modify mitochondrial function. NO2-FA derivatives are present endogenously and mediate anti-inflammatory effects through predominately cGMP–independent mechanisms that include electrophilic posttranslational protein modification and potent peroxisome proliferator-activated receptor (PPARg) ligand activity. As a result of robust thiol reactivity, NO2-FA also activate phase II enzyme expression in vitro and in vivo (e.g., heme oxygenase 1, HO-1), through nuclear factor E2-related factor 2 (Nrf2) activation of antioxidant response element (ARE) dependent gene expression. To summarize, generation of NO2-FA can impact mitochondrial respiratory function, myocardial efficiency, and cardiac contractility in diabetes. And although NO2-FA are endogenously generated as adaptive cell signaling mediators, therapeutic administration (in higher doses than endogenous concentrations) is of interest as to potentially attenuate hyperglycemia and hyperglycemic-induced myocardial injury.