David R. Harder, PhD

Kohler Co. Professor in Cardiovascular Research and Associate Dean for Research; Professor of Physiology, Medicine and Pediatrics; Director for Mentoring, Clinical and Translational Science Institute

Locations

Physiology

Contact Information

Biography

Education

PhD, Biophysics, Medical College of Wisconsin, 1976
MS, Physiology, Medical College of Wisconsin, 1975

Research Interests

Cardiovascular Physiology | Molecular and Cellular Physiology | Neurophysiology

Electrophysiology of excitable tissues

- Ion channels

- Voltage gated mechanisms

- Receptor operated mechanisms

Cellular mechanisms controlling cerebral blood flow

Mechanisms responsible for myogenic activation of arteries

Endothelial dependent mechanisms in vascular smooth muscle

Biochemistry and molecular biology of membrane lipids in vascular muscle, neurons and their effect on ion channels

Cytochrome P450 metabolites in the control of vascular smooth muscle and endothelium

Control of renal blood flow

Mechanisms controlling autoregulation of blood flow

Role of ionic mechanisms in activating arterial and arteriolar smooth muscle

Tumor angiogenesis in the brain – behavioral study

Work done on current grants:

Autoregulation of Cerebral Blood Flow
The main goal of this project is to define the genetic factor responsible for autoregulation of cerebral blood flow, including the signaling cascades and ionic mechanisms that mediate pressure-induced myogenic tone.

Astrocyte Secretome: Ability to Modify Phenotype and Genotype of Cells within the CNS
The goal of this project is to identify the factors released by astrocytes and the differences in the cellular components in the newly born vs adult rat.

NIH Biosketch (PDF)

Upregulation of 20-HETE Synthetic Cytochrome P450 Isoforms by Oxygen-Glucose Deprivation in Cortical Neurons.

(Zhang H, Falck JR, Roman RJ, Harder DR, Koehler RC, Yang ZJ.) Cell Mol Neurobiol. 2017 Oct;37(7):1279-1286.
Inhibition of soluble epoxide hydrolase augments astrocyte release of vascular endothelial growth factor and neuronal recovery after oxygen-glucose deprivation.

(Zhang Y, Hong G, Lee KS, Hammock BD, Gebremedhin D, Harder DR, Koehler RC, Sapirstein A.) J Neurochem. 2017 03;140(5):814-825.
Detection of TRPV4 channel current-like activity in Fawn Hooded hypertensive (FHH) rat cerebral arterial muscle cells.

(Gebremedhin D, Zhang DX, Weihrauch D, Uche NN, Harder DR.) PLoS One. 2017;12(5):e0176796.
Expression of CYP 4A ω-hydroxylase and formation of 20-hydroxyeicosatetreanoic acid (20-HETE) in cultured rat brain astrocytes.

(Gebremedhin D, Zhang DX, Carver KA, Rau N, Rarick KR, Roman RJ, Harder DR.) Prostaglandins Other Lipid Mediat. 2016 07;124:16-26.
Contribution of epoxyeicosatrienoic acids to the cerebral blood flow response to hypoxemia.

(Liu X, Gebremedhin D, Harder DR, Koehler RC.) J Appl Physiol (1985). 2015 Nov 15;119(10):1202-9.
Elevated Aminopeptidase P Attenuates Cerebral Arterial Responses to Bradykinin in Fawn-Hooded Hypertensive Rats.

(Hye Khan MA, Sharma A, Rarick KR, Roman RJ, Harder DR, Imig JD.) PLoS One. 2015;10(12):e0145335.
Correction: Astrocytes Directly Influence Tumor Cell Invasion and Metastasis In Vivo.

(Wang L, Cossette SM, Rarick KR, Gershan J, Dwinell MB, Harder DR, Ramchandran R.) PLoS One. 2015;10(8):e0137369.
Rhythmic expression of cytochrome P450 epoxygenases CYP4x1 and CYP2c11 in the rat brain and vasculature.

(Carver KA, Lourim D, Tryba AK, Harder DR.) Am J Physiol Cell Physiol. 2014 Dec 01;307(11):C989-98.
Enhanced large conductance K+ channel activity contributes to the impaired myogenic response in the cerebral vasculature of Fawn Hooded Hypertensive rats.

(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.
Zinc-finger nuclease knockout of dual-specificity protein phosphatase-5 enhances the myogenic response and autoregulation of cerebral blood flow in FHH.1BN rats.

(Fan F, Geurts AM, Pabbidi MR, Smith SV, Harder DR, Jacob H, Roman RJ.) PLoS One. 2014;9(11):e112878.
Expression of CYP 4A ω- hydroxylase and formation of 20-hydroxyeicosatetreanoic acid (20-HETE) in cultured rat brain astrocytes

(Gebremedhin D, David Zhang X, Carver K, Rau N, Roman, R, Harder DR.) Elsevier . .
Inhibition of soluble epoxide hydrolase augments astrocyte release of vascular endothelial growth factor and neuronal recovery after oxygen –glucose deprivation

(Zhang Y, Hong G, Lee KS, Hammock B, Gebremedhin D, Koehler R, Harder DR, Sapirstein A.) Journal of Neurochemistry. .

David R. Harder, PhD