• Problems Viewing This Page?
• |
• KHRI Home
• |
• Otorhinolaryngology Home
• |
• UMHS Home
• |
• UMich Home
• |
• Site Map

Search WWW KHRI only

Kresge Hearing Research Institute

Department of Otolaryngology

Faculty List

• Altschuler, Richard A.
• Carey, Thomas E.
• Dolan, David F.
• Downs, Catherine
• Duncan, R. Keith
• Gong, Tzy-Wen L.
• Green, Glenn E.
• King, W. Michael
• Kohrman, David C.
• Le Prell, Colleen
• Lesperance, Marci M.
• Lomax, Margaret I.
• Macpherson, Ewan A.
• Middlebrooks, John C.
• Miller, Josef M.
• Pfingst, Bryan E.
• Raphael, Yehoash
• Schacht, Jochen
• Sha, Su-Hua
• Shore, Susan

Retired and Emeritus

• Anderson, David
• Bledsoe, Sanford
• Hawkins, Joseph
• Lawrence, Merle
• Moody, David
• Stebbins, William

Faculty

Dr. Tzy-Wen L. Gong

Research Investigator, Molecular Biology Laboratory
E-mail:
Phone: (734) 763-7755

Accomplishments

• B.A. in Nutrition, Taipei Medical College, Taipei, Taiwan, 1983
• M.S. in Human Nutrition, The University of Michigan, Ann Arbor, MI, 1985
• Ph.D. in Nutrition, University of California-Davis, CA, 1990
• Post-Doc in Physiology, The University of Michigan, Ann Arbor, MI, 1990-1994
• Post-Doc in Otolaryngology, Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI, 1994-1999
• Research Investigator in Otolaryngology, Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI, 1999-present

Research Interests

1. Role of ubiquitin ligase UBE3B in response to noise trauma in the chick inner ear

The avian auditory system has an ability to regain its function after noise or drug insult. This ability is achieved by repair of damaged cells, re-population of lost hair cells, and reconnection of the auditory nerve to new hair cells. In mammals, lost hair cells are not replaced and hearing loss is permanent. In an effort to understand molecular events following noise trauma, we identified a novel molecule UBE3B whose expression increases dramatically in the damaged region of the chick cochlea. UBE3B gene encodes a novel ubiquitin ligase involved in a process that targets proteins for degradation. Involvement of ubiquitin-mediated protein degradation in response to insults has never been implicated previously and represents a new area in the auditory research. We hypothesize that noise-induced UBE3B-mediated ubiquitination occurs in certain cell types that are susceptible to noise insult. We propose to take molecular and biochemical approaches to identify the cell types with increased expression of UBE3B after noise trauma and to identify the proteins targeted for ubiquitination. This will lead to discovery of molecular events affected by noise trauma in the avian auditory system and may provide invaluable information in the underlying mechanisms of repair and regeneration.

2. Molecular mechanism in age-related hearing loss

Presbycusis (age-related hearing loss) and dis-equilibrium are common problems among the elderly. Audiological assessments have greatly facilitated our understanding of presbycusis. I am interested in the molecular mechanism underlying age-related hearing loss using mouse models exhibiting hearing loss with age. Comparisons of gene expression levels among different age groups will provide clues to possible pathways/molecular mechanisms involved in deterioration of auditory function with age. Changes in global gene expression profiling are determined using Affymetrix GeneChip microarrays and verified by RT-qPCR. Further studies of some of these pathways are under way.

Vestibular defects in aging

In contrast to the well-defined biological problems of presbycusis, there is very limited understanding of age-related vestibular dysfunction. With many structural and cellular similarities between the auditory and vestibular systems, I hypothesize that the auditory and vestibular systems undergo similar molecular deterioration over time. The first step in exploring molecular changes in the vestibular system will be to identify proper mouse models. In a pilot study funded by The Claude Pepper Older Americans Independence Center, University of Michigan, I propose to perform a battery of vestibular and auditory functional tests in a 9-month study in 3 strains of mice with hearing loss ranging from early to late onset that represent the whole spectrum of presbycusis in humans. This study will evaluate proper and sensitive functional tests for vestibular integrity; it may also uncover the first animal model(s) of vestibular disorders in aging.

Recent Research Funding

• Agency: The Claude Pepper Older Americans Independence Center, University of Michigan
  Principal Investigator: Tzy-Wen Gong
  7/01/02-6/30/03
  "Auditory and vestibular defects in aging" We propose to explore functional correlations between the vestibular and auditory systems by performing a battery of functional tests in a 9-month longitudinal study in 3 strains of mice with hearing loss ranging from early to late onset that represent the whole spectrum of presbycusis in humans.
  
• Agency: Deafness Research Foundation (DRF)
  Principal Investigator: Tzy-Wen Gong
  7/1/04-6/30/06
  "Role of ubiquitin ligase UBE3B in response to noise trauma in the chick inner ear". We propose to determine the role of UBE3B a novel protein in the ubiqutination pathway in the auditory sensory epithelium effects by determining cell types with increased expression in response to noise trauma and by identifying protein targets of UBE3B-mediated ubiquitination.
  

Publications

• Tsai A.C. and T.-W. Gong (1987) Modulation of the Exercise and Retirement Effects by Dietary Fat Intake in Hamsters. J Nutr 117: 149-1153.
• Gong T.-W.L., B.A. Horwitz, and J.S. Stern (1990) The Effects of 2-Deoxyglucose and Sympathetic Denervation on Brown Fat GDP Binding in Sprague?Dawley Rats. Life Sci. 46: 1037-1044.
• Gong T, B.A Horwitz, and J.S. Stern. (1990) High Fat Feeding Increases Brown Fat GDP Binding in Lean But Not Obese Zucker Rats. J Nutr 120: 786-792.
• Bilir B.M., T.-W.L. Gong, V. Kwasiborski, C.S. Shen, C.S. Fillmore, C.M. Berkowitz, and J.J. Gumucio. (1993) Novel control of the position-dependent expression of genes in hepatocytes: the Glut-1 transporter. J Biol Chem 268: 19776-19784.
• Gong, T.-W.L., A.D. Hegeman, J.J. Shin, H.J. Adler, Y. Raphael. and M.I. Lomax (1996) Identification of genes expressed after noise exposure in the chick basilar papilla. Hear. Res. 96, 20-32.
• Gong, T.-W.L, M. Burmeister, and M.I. Lomax (1996) The novel gene D4Mil1e maps to mouse Chromosome 4 and human Chromosome 1p36. Mammalian Genome 7, 790-791.
• Besirli, C., T.-W.L. Gong, and M.I .Lomax (1997) Novel ß3 isoform of the Na,K-ATPase ß subunit from mouse retina. Biochim. Biophys. Acta, 1350, 21-26.
• Gong, T.-W.L, J.J. Shin, M. Burmeister, and M.I. Lomax (1997) Complete nucleotide sequence of chicken cochlea and mouse liver CDC42 cDNAs. Biochim. Biophys. Acta, 1352, 282-292.
• Gong, T.-W.L., A.D. Hegeman, J.J. Shin, K.H. Lindberg, K.F. Barald, and M.I. Lomax (1997) Novel genes expressed in the chick otocyst and in the basilar papilla after noise: Identification by differential display of mRNA. Invited paper for special issue of Internat. J. Devel. Neurobiol. 15, 585-594.
• Drozdowski, B., T.-W.L. Gong, and M.I. Lomax (1998) The chicken cDNA for ornithine decarboxylase antizyme. Biochim. Biophys. Acta, 1396, 21-26.
• Besirli, C.G., T.-W.L. Gong, and M.I. Lomax (1998) The Atp1b3 gene for the Na,K- ATPase ß3 isoform maps to mouse Chromosome 9 and a related gene, Atp1b3-rs, maps to mouse Chromosome 3. Mammal Genome, 9, 171-172.
• Lomax, M.I., S.J. Warner, C.G. Besirli, and T.-W.L. Gong (1998) The gene for a RING zinc finger prtoein is expressed in the chick inner ear after noise exposure. Primary Sensory Neuron, Highlights in Hair Cell Biology, 2, 229-316.
• Gong T-W.L., D.J. Meyer, J. Liao, C.L. Hodge, G.S. Campbell, X. Wang, N. Billestrup, C. Carter-Su, J. Schwartz. (1998) Regulation of glucose transport and c-fos and egr-1 expression in cells with mutated or endogenous growth hormone receptors. Endocrinology 139:1863-1871.
• Adler, H.J., R.S. Winnicki, T.-W.L. Gong, and M.I. Lomax. (1999) A gene upregulated in the acoustically damaged chick basilar papilla encodes a protein with WD40 repeats.   Genomics, 56:59-69.
• Gong, T.-W.L, R.S. Winnicki, D.C. Kohrman, and M.I. Lomax (1999) A novel mouse kinesin of the Unc-104/KIF1 subfamily encoded by the Kif1b gene. Gene, 239:117-127.
• Stover, T., T.-W.L. Gong, Y. Cho, R.A. Altschuler, and M.I. Lomax (2000) Expression of the GDNF family members ad their receptors in the mature rat cochlea. Mol Brain Res 76, 25-35.
• Lomax, M.I., L. Huang, Y. Cho, T.-W.L. Gong, and R.A. Altschuler. (2000) Differential Display and Gene Arrays to Examine Auditory Plasticity. Hearing Res 147, 293-302.
• Lomax, M.I., T.-W.L. Gong, Y. Cho, L. Huang, S.H. Oh, H.J. Adler, Y Raphael, and RA Altschuler (2001) Differential gene Expression Following Noise Trauma in Birds and Mammals. Noise & Health, 11:19-35.
• Stover, T, TW-L Gong, Y Cho, RA Altschuler, and MI Lomax. (2001) Glial cell line-derived neurotrophic factor (GDNF) and its receptor complex are expressed in mature rat cochlea. Hearing Research, 155:143-151.
• Gong, T.-W.L., C.G. Besirli, R.S. Winnicki, and M. I. Lomax (2001) MACF1 gene structure: a hybrid of plectin and dystrophin. Mammalian Genome, 12, 852-861.
• Cho, Y, T-W L Gong, T Stover, MI Lomax, and RA Altschuler (2002) Gene expression profiles in the rat auditory system. JARO 3 (1), 54-67
• Gong, T.-W. L., L. Huang, S.J. Warner, and M. I. Lomax (2003) Characterization of the human UBE3B gene: Structure, expression, evolution and alternative splicing. Genomics 82 (2),143-52.
• Nair, TS, Kozma, KE, Hoefling, NL, Kommareddi PK, Ueda, Y, Gong, T-W., Lomax, MI, Lansford, CD, Telian, S, Satar, B, Arts, HA, El-Kashlan, H, Berryhill, W, Raphael, , Y, Carey, TE. (2004) Identification and characterization of choline transporter-like protein 2, an inner ear glycoprotein of 68 and 72 kDa that is the target of antibody-induced hearing loss. J Neurosci. 24 (7), 1772-9.
• Cho, Y, T-W Gong, A. Kanicki, RA Altschuler, MI Lomax. (2004) Noise Overstimulation Induces Immediate Early Genes in the Rat Cochlea. Molecular Brain Research 130, 134-148.
• Gong S-G, T-W Gong, L. Shum. Identification of Markers of the Midface. (2005) J Dental Res. 84, 69-72.
• Behnan SM, G Chiao, T-W Gong, L Shum, S-G Gong, (2005) Gene and protein expression of Transforming growth factor ß2 gene during murine primary palatogenesis. Differentiation 73, 233-9.
• Abrashkin KA, M Izumikawa, T Miyazawa, C-H Wang, M Crumling, DL Swiderski, LA Beyer, T-W L Gong, Y Raphael. (2006) The fate of outer hair cells after acoustic or ototoxic insults. Hear Res (in press)
• Gong T-W L, IJ Karolyi, J MacDonald, L Beyer, Y Raphael, DC Kohrman, SA Camper, MI Lomax. (2006) Age-related Changes in Cochlear Gene Expression in Normal and shaker 2 Mice. J Assoc Res Otolaryngol (in press)

Recent Abstracts and Presentations

• Gong, T-W, Y Cho, A Kanicki, G Dootz, D Dolan, RA Altschuler, MI Lomax molecular analysis of noise-induced hearing loss. Presented at 41st Inner Eear Biology Meeting. (Debrecen, Hungary, September 5-7 2004).
• Lomax, CA, T-W Gong, D Fairfield, RA Altschuler, MI Lomax. Role of hsf1 and heat shock proteins in the rodent cochlea. Presented at Inner Ear Biology Meeting. 41st Inner Eear Biology Meeting. (Debrecen, Hungary, September 5-7 2004).
• Gong, T-W L, IJ Karolyi, J MacDonald, DC Kohrman, SA Camper, MI Lomax. Age-dependent changes in cochlear gene expression. Presented at: the 5th Molecular Biology of Hearing and Deafness (Bethesda, MD, September 30-October 3, 2004)
• Lomax, CA, T-W Gong, DA Fairfield, RA Altschuler, MI Lomax. Role of hsf1 and heat shock proteins in the normal and aging rodent cochlea Presented at: the 5th Molecular Biology of Hearing and Deafness (Bethesda, MD, September 30-October 3, 2004)
• Gong, T-W, Y Cho, A Kanicki, G Dootz, D Dolan, RA Altschuler, MI Lomax.. Molecular analysis of noise-induced hearing loss. Presented at: the 5th Molecular Biology of Hearing and Deafness (Bethesda, MD, September 30-October 3, 2004)
• Lomax MI, T-W Gong, G Dootz, L Fullarton, L Kabara, D Fairfield, K Mitchem, CA Lomax, DF Dolan, DC Kohrman, RA Altschuler. Induction of Heat Shock Proteins by Heat And Noise Stress In the Normal and Aging Mouse Cochlea. Presented at the 2005 Midwinter Meeting of Association for Research in Otolaryngology (New Orleans, Louisiana, February, 2005).
• Gong T-W, G Dootz, L Fullarton, K Hunker, CA Lomax, DF Dolan, DC Kohrman, RA Altschuler, MI Lomax. Induction of heat shock proteins by heat and noise stress in the normal, aged, and Hsf1 knockout mouse cochlea. Presented at: Gordon Conference (Newport, Rhode Island, July16-22, 2005).
• Gong T-W, L Fullarton, A Kanicki, G Dootx, D Dolan, R Altschuler, MI Lomax. Induction of heat shock proteins by noise stresses in normal and Hsf1 knockout mice. Presented at the 2006 Midwinter Meeting of Association for Research in Otolaryngology (Baltimore, Maryland, February 5-9, 2006).
• Mileski A, C Guo, S-G Gong, MI Lomax, T-W Gong. Expression of ubiquitin ligase Ube3b in early postnatal mouse teeth, eyes, and cochleae. Presented at the 2006 Midwinter Meeting of Association for Research in Otolaryngology (Baltimore, Maryland, February 5-9, 2006).
• Mustapha-Chail M, Q Fang, LA Beyer, J Karolyi, M Izumikawa, G Dootz, T-W Gong, MI Lomax, D Dolan, Y Raphael, S Camper. Effects of thyroid hormone deficiency on cochlear development and function. Presented at the 2006 Midwinter Meeting of Association for Research in Otolaryngology (Baltimore, Maryland, February 5-9, 2006).
• Crumling M, K Abrashkin, M Izumikawa, T-W Gong, DL Swiderski, Y Raphael. The Fate of degenerated outer hair cells: prestin in supporting cells. Presented at the 2006 Midwinter Meeting of Association for Research in Otolaryngology (Baltimore, Maryland, February 5-9, 2006).
• Gong T-W, S-G Gong, A Mileski, C Guo, K Duncan, MI Lomax,. Expression of ubiquitin ligase Ube3b in the mouse and the chick. To be presented at the 65th Annual Meeting of Society of Developmental Biology, Ann Arbor, Michigan, June 16-21, 2006.