Kimberly Raines-Isler, Ph.D.


Pharmaceutical Science, UMB 2006

Area of Doctoral Study: Pharmaceutical Science
Undergraduate Institute: Duke University
Research Advisor: Dr. Gerald Rosen, UMB

Current Position: Senior Pharmacologist, Center for Drug Evaluation and Research, Food and Drug Administration

Description of Research

My research area focuses on the signal transduction pathway initiated by a family of enzymes, nitric oxide synthase (NOS). NOS is a heme-containing enzyme that catalyzes the oxidation of L-arginine to nitric oxide (NOo) and L-citrulline via the intermediate Nw-hydroxyl-L-arginine. There are three distinct isoforms of this enzyme that are regulated by distinct genes: a constitutive neuronal NOS (nNOS or NOS I) and a constitutive endothelial NOS (eNOS) and an endotoxin- or cytokine-inducible NOS (iNOSor NOS II). NOS also has the unique ability to produce another free radical, superoxide (O2o-), in the absence of its substrate, L-arginine. NOS is involved in a diverse array of cellular functions. In the case of iNOS, a high level of NOo for prolonged periods of time is consistent with its role in host defense. In contrast, the production of NOo by eNOS and nNOS is at a much lower level and is believed to be a transient cell signaling agent. For example, NOS production of NOo activates soluble guanylate cyclase (sGC) and cyclic guanosine monophosphate (cGMP), which are important messenger molecules that mediate a wide variety of physiological functions. These functions include, for instance, the regulation of vascular tone, platelet aggregation, inflammation, neurotransmission, learning and memory, penile erection, gastric emptying, and hormone release. Although many roles of NO· have been established, the mechanism of cell activation has not yet been characterized. My research, will examined regulation of the various cell signaling pathways, including the mitogen activated protein (MAP) kinase pathway, by NOS under conditions where this enzyme generates either NO· or O2o-, with the goal of understanding NO· signal transduction pathways.