David R. Harder, PhD
Associate Dean for Research Mentoring
Professor, Physiology, Medicine, and Pediatrics
Kohler Co. Professor in Cardiovascular Research
Phone: (414) 955-2203 or (414) 955-8200
Molecular and Cellular Physiology
Dr. David R. Harder's research interests are centered on characterization of the cellular and molecular mechanisms of muscle cell contraction, particularly arteriole muscle, and the modification of these mechanisms by endothelial factors, neurotransmitters, and endogenous vaso-active agents. We use intracellular electrophysiological recording from muscle cells within intact arterial segments utilizing standard glass microelectrodes to study these phenomena. Cultured vascular muscle and endothelial cells are studied by voltage and patch-clamp techniques for analysis of ionic events.
"Vascular Signaling by Free Radicals" is one of our group's initiatives. Free radicals are highly reactive agents produced in normal biological processes through the body's use of oxygen. This vascular biology initiative is analyzing how free radicals induce cell death within vessels, and how they modify normal vascular function. Another initiative focuses on the mechanisms controlling cerebral circulation and disease states such as stroke and neuronal damage found in Alzheimer's disease. Two clinical trials underway in the Cardiovascular Center involve the study of gliomas, tumors that originate in the brain or spinal cord. Center investigators are testing specific drugs that may lead to therapies that will reduce or eliminate the tumors.
Selected Recent Publications
Koehler RD, Roman RJ, Harder, DR. Astrocytes and the regulation of cerebral blood flow. Trends in Neurosciences. 2009, 32:160-169
Marija Renic, Judith A. Klaus, Tomohiro Omura, Naoya Kawashima, Michihito Onishi, Noriyuki Miyata, Raymond C. Koehler, David R Harder, and Richard J Roman. Effect of 20-HETE inhibition on infarct volume and cerebral blood flow after transient middle cerebral artery occlusion. J Cereb Blood Flow Metab. 2009, 29:629-639
Kathryn M. Dunn, Marija Renic, Averia K. Flasch, David R Harder, John Flack. Elevated production of 20-HETE in the cerebral vasculature contributes to severity of ischemic stroke and oxidative stress in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol 295: H2455-H2465, 2008.
Stowe DF, Camara AK, Heisner, JS, Aldakkak, M, Harder, D.R. Low-flow Perfusion of Guinea Pig Isolated Hearts with 26°C Air-saturated Lifor® Solution for 20 House Preserves Function and Metabolism. J Heart and Lung Transplantation. 2008, 27(9):1008-15.
Athirakul K, Bradbury Dagger JA, Graves JP, Degraff LM, Ma J, Zhao Y, Couse JF, Quigley R, Harder DR, Zhao X, Imig JD, Pederson TL, Newman JW, Hammock BD, Conley AJ, Korach KS, Coffman TM, Zeldin DC. Increased blood pressure in mice lacking cytochrome P450 2J5. FASEB J. 2008,22:4096-4108
Publications as listed in PubMed