To serve patients, health care providers, research scientists, scholars, and society by providing excellence and innovation in diagnostic services and educational resources in a respectful, professional and culturally diverse atmosphere.
To become a preeminent leader in academic anatomic and clinical pathology while translating basic science discovery to improved clinical care.
Su-Hua Sha, M.D.
Assistant Professor, Department of Pathology & Laboratory Medicine
Office: Walton Research Building Room 403-E
Phone: (843) 792-8324
Fax: (843) 792-0368
B.A., Medicine and Medical License, Tongji Medical University, Wuhan, China, 1983
M.D., Medicine, University of Essen Medical School, Essen, Germany, 1994
Residency, Otolaryngology, Tongji Medical University, Wuhan, China, 1983-1989
Fellowship, Otolaryngology, Tongji Medical University, Wuhan, China, 1989-1991
Visiting Fellow, Otolaryngology, University of Essen, Essen, Germany, 1992-1994
PostDoctoral Fellow, Kresge Hearing Research Institute, University of Michigan, 1994-1997
Assistant Professor, Otolaryngology, Tongji Medical University, Wuhan, China, 1994-1997
Research Associate, Kresge Hearing Research Institute, University of Michigan, 1998-2001
Research Investigator, Kresge Hearing Research Institute, University of Michigan, 2001-2010
Assistant Professor, Department of Pathology and Laboratory Medicine, The Medical University of South Carolina, 2010-present
Regulation of cell survival and cell death signalling in the inner ear
Molecular mechanisms of acquired hearing loss with a focus on noise trauma
Prevention of acquired hearing loss
Our research is focused on redox-regulated signal transduction pathways in noise-induced hearing loss. It is one of our goals to elucidate molecular mechanisms that determine cell death and survival of inner ear sensory cells. The other goal is to translate our basic research findings into clinical therapies to prevent or ameliorate the adverse effects of noise-exposure on the auditory system. In addition, my laboratory is interested in other forms of acquired hearing loss such as aminoglycoside-induced and age-related hearing loss.
NOISE-INDUCED HEARING LOSS:
It may be surprising that the auditory system - designed to process acoustic information - is sensitive to intense sound. Today noise-induced hearing loss is a major and increasing problem in industrialized countries stemming both from the work place and from leisure activities. While most of the public is aware of the dangers of factory and machinery noises, gun shots and airplanes, many seem to disregard the dangers to their hearing of techno and disco music and "walkmen" at high volume. Tinnitus (ringing in the ears), temporary elevation in hearing threshold and permanent hearing loss are possible consequences.
Our current work focuses on two topics. One concerns the initial events following noise exposure which may involve the enhanced formation of reactive oxygen species and therefore upset the redox balance of the cell. The second focus is on the resulting signaling pathways, their transcription factors, and the eventual effects on gene expression.
Interestingly, several inner ear pathologies appear to share oxidative stress as a common feature. We therefore are extending our studies to drug-induced and age-related hearing loss. Both in vivo and in vitro studies from our laboratories have convincingly shown that oxidative stress is a causative factor in aminoglycoside-induced hearing loss and that this “ototoxicity” can be attenuated by the administration of antioxidants. We have been collaborating with Dr. Jochen Schacht at the University of Michigan on the basic mechanisms and with colleagues at the Department of Otolaryngology at Xijing Hospital in Xi'an, China, on a clinical study to protect against gentamicin-induced hearing loss. The successful results were published in the New England Journal of Medicine (354:1856-1857, 2006). We are now trying to improve on this protective therapy.
We have also collaborated in program project grant studying the mechanism of presbycusis (age-related hearing loss) together with other groups at the Kresge Hearing Research Institute and the Geriatrics Center at the University of Michigan. Our studies involve the determination of free radical formation and cochlear antioxidant defenses as well as redox-sensitive homeostatic signaling pathways which engage protein kinases and phosphatases. Cell death pathways are also part of our effort to understand hair cell death in the aging ear.
Sha, S-H. Schacht, J. Are aminoglycoside antibiotics excitotoxic? NeuroReport 9:3893-3895, 1998.
Sha, S-H. Schacht, J. Formation of reactive oxygen species following bioactivation of gentamicin. Free Radical Biol. Med. 26:341-347, 1999.
Sha, S-H. Schacht, J. Stimulation of free radical formation by aminoglycoside antibiotics. Hear. Res. 128:112-118, 1999.
Sha, S.H. Schacht, J. Antioxidants attenuate gentamicin-induced free-radical formation in vitro and ototoxicity in vivo: D-methionine is a potential protectant. Hear. Res. 142:34-40, 2000.
Sinswat, P., Wu, W-J., Sha, S-H. and Schacht, J. Protection from ototoxicity of intraperitoneal gentamicin in guinea pig. Kidney Int. 58:2525-2532, 2000.
Sha, S-H., Taylor, R., Forge, A., Schacht, J. Differential vulnerability of basal and apical hair cells is based on intrinsic susceptibility to free radicals. Hear. Res. 155:1-8, 2001.
Sha, S-H., Zajic, G., Epstein CJ., Schacht, J. Overexpression of SOD protects from kanamycin-induced hearing loss. Audiol. Neuro-Otol. 6:117-123, 2001.
Wu, W-J., Sha, S-H., McLaren, J.D., Kawamoto, K., Raphael, Y., Schacht, J. Aminoglycoside ototoxicity in adult CBA, C57BL and BALB mice and the Sprague-Dawley rat. Hear. Res. 158:165-178, 2001.
Li, G., Sha, S-H., Zotova, E., Arezzo, J., Van De Water, T., Schacht, J. Salicylate protects hearing and kidney function from cisplatin (CDDP) toxicity without compromising its oncolytic action. Lab. Invest. 82:585-596, 2002.
Wu, W-J., Sha, S-H., Schacht, J. Recent advances in understanding aminoglycoside ototoxicity and its prevention. Audiol. Neuro-Otol. 7:171-174, 2002.
Wang, A-M., Sha, S-H., Lesniak, W., Schacht, J. Tanshinone (Salviae miltiorrhizae extract) preparations attenuate aminoglycoside-induced free radical formation in vitro and ototoxicity in vivo. Antimicrob. Agents Chemother. 47:1836-1841, 2003.
Kawamoto, K, Sha, S-H, Minoda, R, Izumikawa, M, Kuriyama, H, Schacht, J., Raphael, Y. Antioxidant gene therapy can protect hearing and hair cells from ototoxicity. Molec. Ther. 9:173-181, 2004.
Minami, S.B., Sha, S-H., Schacht, J. Antioxidant protection in a new animal model of cisplatin-induced ototoxicity. Hear. Res. 198:137-143, 2004.
Endo, T., Nakagawa, T., Iguchi, F., Kita, T., Okano, T., Sha S-H., Schacht, J., Shiga, A., Kim, T-S. Ito, J. Elevation of superoxide dismutase increases acoustic trauma from noise exposure. Free Rad. Biol. Med. 38:492-498, 2005.
Jiang, H*., Sha, S-H*., Schacht, J. The NF-kB pathway protects cochlear hair cells from aminoglycoside-induced ototoxicity. J. Neurosci. Res. 79:644-651, 2005.
Jiang, H*., Sha, S-H*., Forge A., Schacht, J. Caspase-independent pathways on hair cell death induced by kanamycin in vivo. Cell Death Diff. 13:20-30, 2006.
Jiang, H*., Sha, S-H*., Schacht, J. Rac/Rho pathway regulates actin depolymerization induced by aminoglycoside antibiotics. J. Neurosci. Res. 83:1544-1551, 2006.
Sha, S-H., Qiu, J-H. Schacht, J. Aspirin to prevent gentamicin-induced hearing loss. New Engl. J. Med. 354:1856-1857, 2006.
Jiang, H*., Sha, S-H*., Schacht, J. Kanamycin alters cytoplasmic and nuclear phosphoinositide signaling in the organ of Corti in vivo. J. Neurochem. 99:269-276, 2006.
Jiang, H., Talaska, A.E., Schacht, J. Sha S-H. Oxidative imbalance in the aging inner ear. Neurobiol. Aging, 28: 1605-1612, 2007.
Samson, J. D,. Wiktorek-Smagur, A., Politanski, P., Rajkowska, E., Pawlaczyk-Luszczynska, M, Dudarewicz, A., Sha, S-H., Schacht, J. and Sliwinska-Kowalska, M. Noise-induced time-dependent changes in oxidative stress in the mouse cochlea and attenuation by d-methionine. Neuroscience 152:146-150, 2008.
Sha, S-H., Kanicki, A., Dootz, G., Talaska, A.E., Halsey, K., Doolan, D., Altschuler, R. and Schacht, J. Age-related auditory pathology in the CBA/J mouse. Hear. Res. 243:87-94, 2008.
Chen, F-Q., Schacht, J., Sha, S-H. Aminoglycoside-induced histone deacetylation and hair cell death in the mouse cochlea, J. Neurochem. 108:1226-1236, 2009.
Sha, S-H., Chen, F-Q., Schacht, J. Activation of cell death pathways in the inner ear of the aging CBA/J mouse. Hear. Res. 254:92-99, 2009.
Sha, S-H., Chen, F-Q., Schacht, J. PTEN attenuates PIP3/Akt signaling in the cochlea of the aging CBA/J mouse. Hear Res. 264(1-2):86-92, 2010.
Beyer LA, Galano MM, Nair TS, Kommareddi PK, Sha S-H, Raphael Y, Carey TE. Age-related changes in expression of CTL2/SLC44A2 and its isoforms in the mouse inner ear. Hear Res. 282(1-2):63-8, 2011.
Chen, F-Q., Hill, Kayla., Guan,Y-J. Schacht, J. Sha, S-H. Activation of apoptotic pathways in the absence of cell death in an inner-ear immortomouse cell line. Hear Res. 248:33-41, 2012.
Sha, S-H, Kanicki A, Halsey K, Wearne KA, Schacht J. Antioxidant-enriched diet does not delay the progression of age-related hearing loss. Neurobiol Aging. 33:1010.e15-1010.e16, 2012
Matt T*, Ng CL*, Lang K*, Sha S-H*, Akbergenov R*, Shcherbakov D*, Meyer M, Duscha S, Xie J, Dubbaka SR, Perez-Fernandez D, Vasella A, Ramakrishnan V, Schacht J, Böttger EC. Dissociation of Antibacterial Activity and Aminoglycoside Ototoxicity in the 4-Monosubstituted 2-Deoxystreptamine Apramycin. PNAS. 109:10984-9, 2012.
Chen, F-Q., Zheng, H-W., Hill, K., Sha, S-H. Traumatic noise activates Rho-family GTPases through transient energy depletion. J Neurosci. 32(36):12421-30, 2012.
Oishi, N., Chen, F-Q. , Zheng, H-W., Sha, S-H. Intra-tympanic delivery of short interfering RNA into the adult mouse cochlea. Hear Res. 296:36-41, 2013.