David Harder Lab
David R. Harder, PhD
Kohler Co. Professor in Cardiovascular Research and Associate Dean for Research
Professor, Department of Physiology
The major focus of our laboratory is to understand mechanisms regulating the cerebral circulation under physiologic and pathophysiologic conditions. Studies in the laboratory are focused around the astrocyte as both a homeostatic sensor and an active regulator that can affect and protect both the cerebral vasculature and neurons. Our research involves identification and characterization of different ion channel types and second messenger systems in glial cells, neurons, cerebral vascular smooth muscle cells, and endothelial cells. Our goal is to increase our knowledge concerning interactions between lipid mediators and ion channels, second messengers, free radicals, and different enzymatic pathways that mediate both physiologic CNS processes and the pathologic changes in cerebral blood flow and in neural cells.
Debebe Gebremedhin, PhD
Associate Professor, Physiology
Our research interests focus in part on investigating the influence of pathophysiological states such as ischemia reperfusion, insulin-dependent diabetes mellitus and Alzheimer's disease on cerebrovascular function. The research areas include physiology of adenosine receptors; patch clamp electrophysiological screening of functions of different ion channel current types including L-type Ca2+ channels, different types of K+ channels, chloride channels, and a variety of TRP channel currents in isolated cerebral vascular smooth muscle cells, endothelial cells, neurons and astrocytes. We also conduct biochemical assay of CYP-derived lipid metabolites, reactive oxygen species, protein kinases and protein phosphatases to elucidate their functional role in different brain cell types.
Kevin R. Rarick, PhD
Research Scientist I
My education and research background is in exercise and cardiovascular physiology on a systems level, including human endocrine system responses to physical stressors. Since joining David Harder’s lab in 2012, I have been fortunate to be able to merge integrative approaches using whole animal models and cellular and molecular techniques with the goal of increasing our fundamental understanding of the complex physiologic processes that occur between the cells of the brain and the vascular system. My research interests include how the cellular components of the neurovascular unit communicate to maintain adequate cerebral blood flow, uncoupling of the neurovascular unit in response to hyperglycemia or oxidative stress, and how alterations in blood flow hemodynamics impact the structure and function of cerebral vessels. To complete these studies we have been developing techniques such as Laser Doppler flowmetry in conscious rats, intravital microscopy of the brain, and neural and vascular cell culture models from adult rats.
Research Associate I
I’m currently in my 31st year at the Medical College of Wisconsin, and have worked with some of the most distinguished principle investigators the research departments have seen. At this time I’ve been very fortunate to work for Dr. Dave Harder in our studies investigating cerebral blood flow autoregulation in conscious animals which has eliminated the confounding effects of anesthesia on blood flow to the brain. I’m responsible for assisting with the day to day operations of the lab and for the surgical preparation of animals and data collection during our experiments. Some of the current techniques we are using include whisker barrel stimulation, imaging brain cells and measuring cerebral blood flow using two-photon microscopy through a cranial window, as well as measuring H2O2/ATP changes in the brain in real time in response to different antagonist and agonists using biosensor probes.
(Zhang H, Falck JR, Roman RJ, Harder DR, Koehler RC, Yang ZJ.) Cell Mol Neurobiol. 2017 Oct;37(7):1279-1286.
(Zhang Y, Hong G, Lee KS, Hammock BD, Gebremedhin D, Harder DR, Koehler RC, Sapirstein A.) J Neurochem. 2017 03;140(5):814-825.
(Gebremedhin D, Zhang DX, Weihrauch D, Uche NN, Harder DR.) PLoS One. 2017;12(5):e0176796.
(Gebremedhin D, Zhang DX, Carver KA, Rau N, Rarick KR, Roman RJ, Harder DR.) Prostaglandins Other Lipid Mediat. 2016 07;124:16-26.
(Liu X, Gebremedhin D, Harder DR, Koehler RC.) J Appl Physiol (1985). 2015 Nov 15;119(10):1202-9.
(Hye Khan MA, Sharma A, Rarick KR, Roman RJ, Harder DR, Imig JD.) PLoS One. 2015;10(12):e0145335.
(Wang L, Cossette SM, Rarick KR, Gershan J, Dwinell MB, Harder DR, Ramchandran R.) PLoS One. 2015;10(8):e0137369.
(Carver KA, Lourim D, Tryba AK, Harder DR.) Am J Physiol Cell Physiol. 2014 Dec 01;307(11):C989-98.
(Pabbidi MR, Mazur O, Fan F, Farley JM, Gebremedhin D, Harder DR, Roman RJ.) Am J Physiol Heart Circ Physiol. 2014 Apr 01;306(7):H989-H1000.
(Fan F, Geurts AM, Pabbidi MR, Smith SV, Harder DR, Jacob H, Roman RJ.) PLoS One. 2014;9(11):e112878.
(Gebremedhin D, David Zhang X, Carver K, Rau N, Roman, R, Harder DR.) Elsevier . .
(Zhang Y, Hong G, Lee KS, Hammock B, Gebremedhin D, Koehler R, Harder DR, Sapirstein A.) Journal of Neurochemistry. .