- BS, University of Tubingen
- PhD, Free University of Berlin
- Postdoc, Oregon Health Sciences University
- Assistant Professor, Neuroscience
Hearing loss is America’s leading disability, affecting millions of people of all ages. To develop preventative and restorative clinical approaches, it is crucial to understand how the hearing process works on the cellular and molecular level. Hearing is mediated by sensory hair cells, part of a highly specialized neuroepithelium in the inner ear. The goal of our lab is to unravel the mechanisms that mediate the development, function, and degeneration of hair cells.
Research focus I: Discovery of novel proteins involved in hearing and deafness
The process of hair cell mechanotransduction converts mechanical energy, caused by sound or head acceleration, into electrical signals that can be interpreted by the brain. This process takes place in the sensory hair cell, in a specialized organelle called hair bundle. Roughly a third of all gene mutations causing hearing loss encode proteins that reside in the sensory hair bundle (Raviv et al., 2010 and hereditaryhearingloss.org). Identification and characterization of hair bundle proteins is thus expected to facilitate the discovery of novel deafness genes. Our lab uses Proteomics methods to identify novel proteins that are located in the hair bundle, and we follow up the initial discovery by an in depth characterization of protein function, using cell biology, molecular biology, protein biochemistry and mouse genetics. Using this multifaceted approach, we have already identified several genes that are involved in hearing loss (e.g. FSCN2), and we are currently working on several novel proteins with possible roles in hearing and deafness.
Research focus II: Neurodegeneration and protection of sensory hair cells
The mechanosensitive hair cells in the inner ear do not regenerate, meaning they cannot be replaced once irreparably damaged and lost. It is therefore crucial to identify measures to protect and repair damaged hair cells. Sensory hair cells are sensitive to many different stress factors, both environmental and endogenous to the cell. Hair cell damage can occur due to age, genetic predispositions, noise and drugs such as certain antibiotics and anti-cancer drugs. A major goal of our lab is to understand the molecular mechanisms and pathways that underlie hair cell damage and death, with special emphasis on drug-induced hair cell damage. Using a combination of cell biology, molecular biology, proteomics and transgenic mouse models, we are probing cellular signaling networks for their involvement in the healthy and pathological state of the sensory hair cell, with the goal of identifying novel pathways and therapeutic targets to prevent hearing loss.
- Francis S, Katz J, Fanning K, Harris K, Nicholas B, Lacy M, Pagana J, Agris P, Shin J. A novel role of cytosolic protein synthesis inhibition in aminoglycoside ototoxicity. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2013;33(7): 3079-93. PMID: 23407963
- Shin J, Krey J, Hassan A, Metlagel Z, Tauscher A, Pagana J, Sherman N, Jeffery E, Spinelli K, Zhao H, Wilmarth P, Choi D, David L, Auer M, Barr-Gillespie P. Molecular architecture of the chick vestibular hair bundle. Nature neuroscience. 2013;16(3): 365-74. PMID: 23334578 | PMCID: PMC3581746
- Grati M, Shin J, Weston M, Green J, Bhat M, Gillespie P, Kachar B. Localization of PDZD7 to the stereocilia ankle-link associates this scaffolding protein with the Usher syndrome protein network. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2012;32(41): 14288-93. PMID: 23055499 | PMCID: PMC3518401
- Spinelli K, Klimek J, Wilmarth P, Shin J, Choi D, David L, Gillespie P. Distinct energy metabolism of auditory and vestibular sensory epithelia revealed by quantitative mass spectrometry using MS2 intensity. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(5): E268-77. PMID: 22307652 | PMCID: PMC3277109
- Zhao H, Williams D, Shin J, Brügger B, Gillespie P. Large membrane domains in hair bundles specify spatially constricted radixin activation. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2012;32(13): 4600-9. PMID: 22457506 | PMCID: PMC3324267
- Shin J, Longo-Guess C, Gagnon L, Saylor K, Dumont R, Spinelli K, Pagana J, Wilmarth P, David L, Gillespie P, Johnson K. The R109H variant of fascin-2, a developmentally regulated actin crosslinker in hair-cell stereocilia, underlies early-onset hearing loss of DBA/2J mice. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2010;30(29): 9683-94. PMID: 20660251 | PMCID: PMC2922854
- Shin J, Streijger F, Beynon A, Peters T, Gadzala L, McMillen D, Bystrom C, Van der Zee C, Wallimann T, Gillespie P. Hair bundles are specialized for ATP delivery via creatine kinase. Neuron. 2007;53(3): 371-86. PMID: 17270734 | PMCID: PMC1839076
- Gagnon L, Longo-Guess C, Berryman M, Shin J, Saylor K, Yu H, Gillespie P, Johnson K. The chloride intracellular channel protein CLIC5 is expressed at high levels in hair cell stereocilia and is essential for normal inner ear function. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2006;26(40): 10188-98. PMID: 17021174
- Senften M, Schwander M, Kazmierczak P, Lillo C, Shin J, Hasson T, Géléoc G, Gillespie P, Williams D, Holt J, Müller U. Physical and functional interaction between protocadherin 15 and myosin VIIa in mechanosensory hair cells. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2006;26(7): 2060-71. PMID: 16481439 | PMCID: PMC2712835
- Shin J, Adams D, Paukert M, Siba M, Sidi S, Levin M, Gillespie P, Gründer S. Xenopus TRPN1 (NOMPC) localizes to microtubule-based cilia in epithelial cells, including inner-ear hair cells. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(35): 12572-7. PMID: 16116094 | PMCID: PMC1194908