Peter Barr-Gillespie, Ph.D.
After undergraduate studies at Reed College, Peter G. Barr-Gillespie attended graduate school at the University of Washington, working with Joe Beavo; he received his PhD in Pharmacology in 1988. From 1988 to 1993, he worked as a postdoc with Jim Hudspeth, first at the UCSF, then at the UT 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 of Otolaryngology, as well as the Vollum Institute; he was promoted to Professor of Otolaryngology in 2004 and granted tenure in 2007. In 2012, Barr-Gillespie was named Director of the Hearing Health Foundation's Hearing Restoration Project (HRP), a consortium of scientists who are developing a strategy for regeneration of sensory hair cells of the inner ear. In 2014, Barr-Gillespie was appointed Associate Vice President for Basic Research at OHSU.
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 bundle, the mechanically sensitive organelle of the hair cell, what are the characteristics of the resulting receptor current? By studying these transduction currents, we learn how transduction channels open and close in response to mechanical forces, how the adaptation motor responds to sustained forces and allows channels to close, and how the cell responds to the high levels of calcium ion that enter. These experiments have led us to identify, for example, the tip link proteins, cadherin 23 and protocadherin 15; the adaptation motors, myosins IC and VIIA; and the calcium pump, plasma-membrane Ca2+-ATPase isoform 2w/a.
We also take a systems-level approach to studying hair cell function, as the hair bundle assembles and transduces due to the coordinated activity of hundreds of proteins. To carry out this analysis, we exploit modern technological advances in proteomics and genomics, which are remarkably powerful in their ability to comprehensively identify and accurately quantify molecules and which have the sensitivity to detect scarce hair-cell proteins and transcripts.
We have applied proteomics techniques to every aspect of the lab's research program, determining with increasing accuracy the hair bundle's proteome and investigating how it changes in response to genetic and pharmacological manipulations. Now that we know the several hundred most abundant proteins of the hair bundle, we have begun to dissect how the hair bundle is assembled during development and regeneration of hair cells following damage. Finally, 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
Powers, R.J., Roy, S., Atilgan, E., Brownell, W.E., Sun, S.X., Gillespie, P.G., and Spector, A.A. (2012). Stereocilia membrane deformation: implications for the gating spring and mechanotransduction channel. Biophys. J. 102, 201-210. PMCID: PMC3260783
Spinelli, K.J., Klimek, J.E., Wilmarth, P.A., Shin, J.-B., Choi, D., David, L.L., and Gillespie, P.G. (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. PMCID: PMC3277109
Zhao, H., Williams, D.E., Shin, J.-B., Brügger, B., and Gillespie, P.G. (2012). Large membrane domains in hair bundles specify spatially constricted radixin activation. J. Neurosci. 32, 4600-4609. PMCID: PMC3277109
Zheng, Q.Y., Scarborough, J.D., Zheng, Y., Yu, H., Choi, D., and Gillespie, P.G. (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. PMCID: PMC3349429
Shin, J.B., Krey, J.K., Hassan, A., Metlagel, Z., Tauscher, A.N., Pagana, J.M., Sherman, N.E., Jeffrey, E.D., Spinelli, K.J., Zhao, H., Wilmarth, P.A., Choi, D., David, L.L., Auer, M., and Barr-Gillespie, P.G. (2013). Molecular architecture of the chick vestibular hair bundle. Nature Neurosci. 16, 365-74. PMCID: PMC3581746
Indzhykulian, A.A., Stepanyan, R., Nelina, A., Spinelli, K.J., Ahmed, Z.M., Belyantseva, I.A., Friedman, T.B., Barr-Gillespie, P.G., and Frolenkov, G.I. (2013). Molecular remodeling of tip links underlies mechanosensory regeneration in auditory hair cells. PLoS Biology 11, e1001583. PMCID: PMC3679001
Avenarius, M.R., Saylor, K.W., Lundeberg, M.R., Wilmarth, P.A., Shin, J.B., Spinelli, K.J., Pagana, J.M., Andrade, L., Kachar, B., Choi, D., David, L.L., and Barr-Gillespie, P.G. (2013). Correlation of actin crosslinker and capper expression levels with stereocilia growth phases. Mol. Cell. Proteomics 13, 606-620. PMCID: PMC3916657
Krey, J.F., Wilmarth, P.A., Shin, J.B., Klimek, J., Sherman, N.E., Jeffery, E.D., Choi, D., David, L.L., and Barr-Gillespie, P.G. (2013). Accurate label-free protein quantitation with high- and low-resolution mass spectrometers. J. Proteome. Res. 13, 1034-1044. PMCID: PMC3946283
Powers, R.J., Kualson, S., Atilgan, E., Brownell, W.E., Sun, S.X., Barr-Gillespie, P.G., and Spector, A.A. (2014). The local forces acting on the mechanotransduction channel in hair cell stereocilia. Biophys. J. 106, 2519-2528. PMCID: PMC4052279
Mo, W., Kindt, K., Maeda, R., Erickson, T., Morgan, C.P., Therneau, A., Clemens-Grisham, R., Barr-Gillespie, P.G., and Nicolson, T. (2014). The tip-link protein protocadherin 15 interacts with transmembrane channel-like proteins. Submitted.
- 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; 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