Peter Gillespie, Ph.D.

Background

After undergraduate studies at Reed College in Portland, Oregon, Peter G. Gillespie attended graduate school at the University of Washington, where he received his Ph.D. in Pharmacology in 1988. He spent five years as a postdoc with Jim Hudspeth, first at the University of California, San Francisco, then at the University of Texas Southwestern Medical Center. He joined the Department of Physiology at Johns Hopkins University as an Assistant Professor in 1993 and rose to Associate Professor in 1998. In 1999 he joined the Oregon Hearing Research Center as an Associate Professor and the Vollum Institute as an Affiliated Scientist. He was promoted to Professor in 2004 and granted tenure in 2007.

Summary of Current Research

We study mechanotransduction by hair cells, the sensory cells of the inner ear. Being interested in what molecules make up the transduction apparatus, the collection of channels, linker molecules, and motors that mediate transduction, we take a frank reductionist approach. We start with physiology: when you mechanically stimulate a hair cell, what are the characteristics of the resulting receptor current? Studying transduction currents, we learn how transduction channels open and close in response to mechanical forces, and how the adaptation motor responds to sustained forces and allows channels to close. These experiments have suggested candidate families for the transduction channel and the adaptation motors, for example, and we use these clues to identify, clone, and characterize the responsible molecules. Because the scarcity of hair cells prevent extensive biochemical characterization, we express transduction molecules in vitro and determine properties that can be compared with the physiology of transduction.

This approach has proven highly successful for identification of the adaptation motor, myosin-1c, the tip link, cadherin-23, and the calcium pump, PMCA2a.  We hope to soon identify the transduction channel, then determine how the cell assembles these and other molecules to make a sensory cell that can responds to deflections of one nanometer or less.

Selected Recent Publications

Siemens, J., Lillo, C., Dumont, R.A., Reynolds, A., Williams, D.S., Gillespie, P.G., and Müller, U. (2004). Cadherin 23 is a component of the tip link in hair cell stereocilia. Nature 428, 950-955.

Hirono, M., Denis, C.S., Richardson, G.P., and Gillespie, P.G. (2004). Phosphatidylinositol-4,5-bisphosphate modulates transduction and adaptation in sensory hair cells. Neuron 44, 309-20.

Stauffer, E., Scarborough, J.D., Hirono, M., Miller, E.D., Shah, K., Mercer, J.A., Holt, J.R., and Gillespie, P.G. (2005). Fast adaptation in vestibular hair cells requires myosin-1c activity. Neuron 47, 541-553.

Hill, J.K., Williams, D.E., LeMasurier, M., Dumont, R.A., Strehler, E.E., and Gillespie, P.G. (2006). Splice-site A choice targets plasma-membrane Ca2+-ATPase isoform 2 to hair bundles. J. Neurosci. 26, 6172-6180.

Hill, J. K., Brett, C. L., Chyou, A., Kallay, L. M., Sakaguchi, M., Rao, R., and Gillespie, P. G. (2006). Vestibular hair bundles control pH with (Na+,K+)/H+ exchangers NHE6 and NHE9. J. Neurosci. 26, 9944-9955.

Shin, J.-B., Streijger, F., Beynon, A., Peters, T., Gadzalla, L., McMillen, D., Bystrom, C., Van der Zee, C.E.E.M., Walliman, T., and Gillespie, P.G. (2007). Hair bundles are specialized for ATP delivery via creatine kinase. Neuron 53, 371-386.

Grillet, N., Xiong, W., Reynolds, A., Kazmierczak, P., Sato, T., Lillo, C., Dumont, R.A., Hintermann, E., Sczaniecka, A., Schwander, M., Williams, D., Kachar, B., Gillespie, P.G., Müller, U. (2009). Harmonin mutations cause mechanotransduction defects in cochlear hair cells. Neuron 62, 375-387.

Education

• B.A. (Chemistry), Reed College, 1981
• Ph.D. (Pharmacology), University of Washington, 1988

Previous Positions

• Postdoctoral Fellow (with Jim Hudspeth), University of California, San Francisco, 1988-1989
• Postdoctoral Fellow (with Jim Hudspeth), University of Texas Southwestern Medical Center, Dallas, 1989-1993
• Assistant Professor (Physiology), Johns Hopkins University, 1993-1998
• Associate Professor (Physiology), Johns Hopkins University, 1998-1999

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