Peter Barr-Gillespie, Ph.D.
Professor of Otolaryngology
Lab Phone: 503-494-2950
Office: MRB 920A
After undergraduate studies at Reed College in Portland, Oregon, Peter G. Barr-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 a Scientist. He was promoted to Professor in 2004 and granted tenure in 2007.
Peter Barr-Gillespie is a member of Hearing Health Foundation’s Hearing Restoration Project (HRP), a consortium of experienced researchers working together to develop a strategy for regeneration of sensory hair cells of the inner ear. Through collaboration, the HRP aims to accelerate the path to a cure for hearing loss by eliminating duplicative work and fostering cooperation rather than competition.
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.
Recently, we have applied proteomics techniques to every aspect of the lab's research program. Modern mass spectrometry is remarkably comprehensive in its ability to identify and quantify molecules and has the sensitivity to detect scarce hair-bundle proteins.
Now that we know the several hundred most abundant proteins of the hair bundle, we can begin to dissect how the hair bundle is assembled during development. Moreover, our knowledge of several proteins of the transduction complex, together with the sensitivity of mass spectrometry, allows us to take a biochemical approach to identification of the transduction channel, one of the central mysteries of the auditory system.
Selected Recent Publications
Shin J-B, Streijger F, Beynon A, Peters T, Gadzalla L, McMillen D, Bystrom C, Van der Zee CEEM, Walliman T, Gillespie PG. (2007) Hair bundles are specialized for ATP delivery via creatine kinase. Neuron 53, 371-386.
Gillespie PG, Müller U. (2009) Mechanotransduction by hair cells: models, molecules, and mechanisms. Cell 139, 33-44.
Shin JB, Longo-Guess CM, Gagnon LH, Saylor KW, Dumont RA, Spinelli KJ, Pagana JM, Wilmarth PA, David LL, Gillespie PG, Johnson KR. (2010) The R109H variant of fascin-2, a developmentally regulated actin crosslinker in hair-cell stereocilia, underlies early-onset hearing loss of DBA/2J mice. J. Neurosci. 30, 9683-9694.
Ren T, He W, Gillespie PG. (2011) Measurement of cochlear power gain in the sensitive gerbil ear. Nature Commun. 2, 216.
Spinelli KJ, Klimek JE, Wilmarth PA, Shin J-B, Choi D, David LL, Gillespie PG. (2012). Distinct energy metabolism of auditory and vestibular sensory epithelia revealed by quantitative mass spectrometry using MS2 intensity. Proc. Natl. Acad. Sci. USA 109, E268-E277.
Zhao H, Williams DE, Shin J-B, Brügger B, Gillespie PG. (2012). Large membrane domains in hair bundles specify spatially constricted radixin activation. J. Neurosci. 32, 4600-4609.
Zheng QY, Scarborough JD, Zheng Y, Yu H, Choi D, Gillespie PG. (2012). Digenic inheritance of deafness caused by 8J allele of myosin-VIIA and mutations in other Usher I genes. Hum. Mol. Genet. 21, 2588-2598.
- B.A. (Chemistry), Reed College, 1981
- Ph.D. (Pharmacology), University of Washington, 1988
- 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