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William  Courchesne , Ph.D.
Associate Professor

William Courchesne

Contact Information

Degrees

  • Postdoctoral Fellow, University of California, Berkeley, 1985-1989
  • Ph.D., Microbiology, Massachusetts Institute of Technology, 1985
  • B.A., Genetics, University of California, Berkeley, 1976

Biography

  • Postdoctoral Fellow, University of California, Berkeley, 1985-1989

Research Interests

The principal research effort in my lab is the characterization of the molecular mechanisms of the antifungal drug amiodarone. We were the first to publish work showing amiodarone has potent antifungal activity against a broad spectrum of fungi and we were the first to publish work showing that amiodarone causes a rise in cytoplasmic calcium in response to alteration of the yeast cell wall. Our work is the first showing effects of this drug, caffeine, and cell wall on calcium ion channels in yeast. UNR holds a patent for use of amiodarone as an antifungal based on my research. Published work now shows amiodarone has antiparasitic activity, including an apparent amiodarone cure of a patient with Chagas disease.

In collaboration with Dr. Elizabeth Hejchman, Department of Medical Chemistry, at The Medical University of Warsaw, Poland, we have synthesized compounds related to amiodarone and tested them for antifungal activity and identified novel antifungal compounds.

Perhaps the most famous and industrially important characteristic of the yeast Saccharomyces cerevisiae is its ability to produce ethanol as a metabolic product and to survive high concentrations of this toxic compound. We hypothesized that ethanol should induce a Ca2+ influx analogous to other stresses. We now have data demonstrating a new signaling response elicited by exposure of yeast cells to ethanol, a dramatic rise in the cytoplasmic Ca2+ concentration ([Ca2+]cyt). The ethanol-induced increase in [Ca2+]cyt is largely dependent on the Cch1/Mid1 Ca2+ channel, and affected by cell wall integrity. Our objective is to reveal the functions of the molecular players and physiological conditions involved in this novel signaling process.

Recent research shows that the mainstay antifungal in clinical use for decades, amphotericin B, also causes calcium flux in yeast cells. We have demonstrated synergistic antifungal activity between amiodarone and amphotericin B.

Selected Publications

  • Copley, K.S., S.M. Alm, D.A. Schooley, and W.E. Courchesne. 1998. Expression, processing, proteolysis and secretion of Manduca sexta diuretic hormone by Saccharomyces cerevisiae. Biochemical J. 330:1333-1340.
  • Dong, H. and W.E. Courchesne. 1998. Use of a novel quantitative mating assay on the fungal pathogen Cryptococcus neoformans provides insight into signalling pathways responding to nutrients and temperature. Microbiology 144:1691-1697.
  • Courchesne, W.E. 2002. Characterization of a novel, broad-based fungicidal activity for the antiarrhythmic drug amiodarone. J.Pharm.Exp.Therap. 300:195-199.
  • Cao, H., W.E. Courchesne, and C.C. Mastick. 2002. A phosphotyrosine-dependent (PY) dihybrid yeast protein interaction screen reveals a role for phosphorylation of caveolin-1 on tyrosine 14: recruitment of CSK to caveolae, J. Biol. Chem. 277:8771-8774.
  • Courchesne, W.E. and S. Ozturk. 2003. Amiodarone induces a caffeine-inhibited, MID1-dependent rise in free cytoplasmic calcium in S. cerevisiae. Mol. Micro., 47:223-234.
  • Courchesne, W.E., M. Tunc, S. Liao. 2009. Amiodarone induces stress responses and calcium flux mediated by the cell wall in S. cerevisiae. Ca. J. Microbiology, 55:288-303.
  • Courchesne, W.E., C. Vlasek, R. Klukovich, and S. Coffee. 2011. Ethanol induces calcium influx via the Cch1-Mid1 transporter in Saccharomyces cerevisiae. Arch. Microbiol. 193:323-334.
  • Hejchman, E., K. Ostrowska, D. Maciejewska, J. Kossakowski, and W.E. Courchesne. 2012. Synthesis and antifungal activity of derivatives of 2- and 3-benzofurancarboxylic acids. J. Pharm. Exp. Therap. 343:380-388.

Courses Taught

  • Medical Microbiology for medical students (MICR 601)
  • Medical Microbiology for undergraduates (MICR 300)
  • Microbial Genomics and Genetics (MICR 350)
  • Microbial Pathogenesis (MICR 470/670)
  • Infectious Diseases (MICR 483)
  • Biotechnology Today and Tomorrow (MICR 700)

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