Image of Horwitz, Joel

Joel Horwitz, PhD

Professor

  • Department:Pharmacology & Physiology
  • Education: PhD, University of Chicago, Chicago, Ill.
Research Overview

Research interests: Dr. Joel Horwitz conducts research in the field of nitric oxide signaling.

Research

One of Dr. Horwitz's research goals is to understand the effects of long-term ethanol exposure on signal transduction in neuronal systems. Long-term ethanol down regulates phospholipase D activity but does not appear to affect the phospholipase C specific for inositol-containing phospholipids. The differential effects of ethanol are due to the uniqueness of each signal transduction pathway. For example, the activation of phospholipase D is mediated by tyrosine kinases, whereas the activation of phospholipase C is mediated by G-proteins. Current research is focused on the role of phosphorylation in mediating the inhibitory effects of ethanol.

Another research goal is to understand the role of free radicals in the etiology of Parkinson’s disease and other neurodegenerative diseases. Dr. Horwitz is particularly interested in peroxynitrite-mediated toxicity to catecholamine containing cells. Peroxynitrite is an oxygen reactive molecule that is formed by the near diffusion-limited reaction of superoxide with nitric oxide. These metabolites are found at high concentrations in the substantia nigra, the area that degenerates in Parkinson’s. Initial studies suggest that peroxynitrite inhibits tyrosine hydroxylase by nitration of a single tyrosine residue near the active site of the enzyme. Dr. Horwitz's lab has also shown that tyrosine hydroxylase is nitrated in an animal model for Parkinson’s. The inactivation of tyrosine hydroxylase represents the initial insult in the progression of this neurodegenerative disease.

Publications

Selected Publications

"Differential effects of long-term ethanol on signal transduction in PC12 cells"
Levine G, Magliano J, and Horwitz J
Alcoholism: Clinical and Experimental Research 24, 93-101 (2000).

"Nitration of a single tyrosine residue accelerates proteolytic degradation of proteins"
Souza JM, Choi I, Chen Q, Daikhin E, Yudkoff M, Obin M, Ara J, Horwitz J, and Ischiropoulos H
Archives Biochem. Biophys. 380, 360-366 (2000).

"Phospholipase D hydrolyzes short-chain analogs of phosphatidylcholine in the absence of detergent"
Horwitz J, Magliano J, and Davis LL
Lipids, 33 223-227 (1998).

"Increased levels of methylated intermediates of phosphatidylcholine lead to enhanced phospholipase D activity"
Jacobs TQ, Passarello B, and Horwitz J
Neurochem Res. 23 1101-1107 (1998).

"Nitration and inactivation of tyrosine hydroxylase at early stages of 1-methyl-4-pheny-1,2,3,6-tetrahydropyridine neurotoxicity: A novel biochemical mechanism for Parkinson’s disease"
Ara J, Horwitz J, Jackson-Lewis V, Naini AB, Przedborski S, Gole M, Malcolm S, Faust R, Gow A, Ischiropoulos H
Proc. Natl. Acad. Sci. USA 95 7659-7663 (1998).

"Peroxynitrite-mediated inhibition of DOPA synthesis in PC12 cells"
Ischiropoulos H, Duran D, and Horwitz J
J. Neurochem. 65 2366-2372 (1995).

Teaching

Dr. Horwitz is a professor in the Department of Pharmacology & Physiology at Drexel University College of Medicine.

Research Location

Department of Pharmacology & Physiology
2900 W. Queen Lane
Room C-9E
Philadelphia, PA 19129
Phone: 215-991-8468

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