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David R. Harder, Ph.D.
Professor of Physiology, Medicine and Pediatrics

Associate Dean for Research

Kohler Co. Endowed Chair

Director for Mentoring CTSI
Phone: (414) 955-8200  
Email: dharder@mcw.edu
M.S. Physiology, Medical College of Wisconsin, 1975
Ph.D. Biophysics, Medical College of Wisconsin, 1976

Research areas: Cardiovascular Physiology
  Neurophysiology
  Molecular & Cellular Physiology


Research Interests:

  • 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.

 

 

Recent Publications:

  • Gebremedhin D, Wickramasekera NT, and  Harder DR (2012). Reactive oxygen species modulate astrocyte and capillary cell functions in the regulation of cerebral blood flow. In: Hand Book of Systems Biology of Oxidative Stress.  In Press.
  • Gebremedhin D, Terashvili M, Wickramasekera N, Zhang DX, Rau N, Miura H, Harder DR (2013). Redox Signaling via Oxidative Inactivation of PTEN Modulates Pressure-Dependent Myogenic Tone in Rat Middle Cerebral Arteries. PLoS One 8(7):e68498. doi: 10.1371/journal.pone.0068498, PMCID: PMC3702596.

 

  • Gebremedhin D, Gopalakrishnan S, Harder DR (2013). Endogenous events modulating myogenic regulation of cerebrovascular function.  Current Vascular Pharmacology 2013 Sep 25, PMID: 24066934.

 

  • Sarkar P,  Zaja I,  Bienengraeber M, Rarick K, Terashvili M, Cornfeild S, Falck JR. Harder DR (2013).  EpoxyeicosaTrienoic acids (EETs) pre-treatment improves amyloid β-induced mitochondrial dysfunction in cultured rat hippocampal astrocytes.  Am J Physiol Heart Circ Physiol. 2013 Nov 27, PMCID: PMC3920242.

 

  • Pabbidi MR, Farley JM, Gebremedhin D, Harder DR, and Roman RJ.  Enhanced large conductance Ca+2 -sensitive K+ channels (BK) activity contributes to the impaired myogenic response in the cerebral vasculature of Fawn Hooded Hypertensive (FHH) rats. Am J Physiol Heart Circ Physiol 2014 Jan 24, PMCID: PMC3962634.

 

  • Wang L, Cossette SM, Rarick KR, Gershan J, Dwinell MB, Harder DR, Ramchandran R. (2013) Astrocytes directly influence tumor cell invasion and metastasis in vivo. PLoS One Dec 4;8(12):e80933. doi: 10.1371/journal.pone.0080933, PMCID: PMC3851470.

 

  • Carver KA, Lourim D, Tryba AK, Harder DR.(2014) Rhythmic expression of cytochrome P450 epoxygenases CYP4X1 and CYP2C11 in the rat brain and vasculature. Am J Physiol Heart Circ Physiol 2014 July 23, PMID: 25055826.

 

 

 

NIH Biosketch

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