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    Douglas A Cotanche PhD

    TitleAssociate Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentCell and Developmental Biology
    AddressUniversity of Massachusetts Medical School
    55 Lake Avenue North, S7-212
    Worcester MA
    Phone508-856-2261
        Overview 
        Narrative
        Cell and Developmental Biology Website

        Academic Background

        BA, University of New Hampshire, 1977
        PhD, University of North Carolina, 1983
        Postdoctoral Fellow, University of Pennsylvania, 1985
        Assistant Professor, Medical University of South Carolina, 1985-87
        Assistant/Associate Professor, Boston University School of Medicine, 1987-1997
        Associate Professor, Children’s Hospital Boston/Harvard Medical School, 1998-2008
        Affiliated Faculty Harvard/MIT Division of Health Sciences & Technology, 2002-2013
        Associate Professor, Boston University School of Medicine, 2008-2010
        Visiting Scientist, Harvard School of Public Health, 2010-2013

        Cochlear Hair Cell Development and Regeneration

        Research Interests

        Research in my laboratory over the last twenty-five years has focused on the development, apoptotic death, and regeneration of sensory hair cells in the avian and mammalian cochlea. In 1986 I discovered that the chicken cochlea is capable of regenerating functional hair cells following noise exposure to replace those that have been lost or damaged due to acoustic trauma. This was quite a surprising finding at the time because previous research had indicated that lost hair cells were irreplaceable and resulted in permanent hearing deficits. Since my initial findings, hair cell regeneration has become the focus of a number of major laboratories throughout the world and has rapidly developed into a clinically relevant and competitive research area. It is believed that an understanding of avian hair cell regeneration will lead directly to clinical applications that can treat genetic, trauma-induced, or age-related hearing loss in humans.

        Recent research projects in my laboratory addressed the mechanisms that regulate hair cell regeneration, i.e., the control of hair cell death, the subsequent proliferation of the supporting cells and the eventual differentiation of new hair cells in the avian cochlea. Normally, the sensory epithelium is composed of a postmitotic population of hair cells and supporting cells. Sound damage and aminoglycoside treatment were utilized experimentally to induce the loss of hair cells through apoptosis, or programmed cell death. The loss of hair cells from the sensory epithelium acts as a signal to re-initiate the cell cycle in the quiescent supporting cells.
        Our research also explored the transplantation of neural stem cells into the damaged mammalian cochlea. We have transplanted mouse neural stem cells into the noise-damaged cochleae of mice and guinea pigs and have shown that the mouse stem cells integrate primarily into the cochlear ganglion where they differentiate into nerves and glial cells, but that they also reach the cochlea where they differentiate into hair cells and supporting cells.

        From 2010 to 2013 I worked in the NIHL Research Group at the Harvard School of Public Health focusing on the impact of noise-induced hearing loss on the performance of Navy Sailors and Marines in military environments. We were exploring the bioavailability of systemically-administered antioxidants and their ability to attenuate hearing threshold shifts. We were also utilizing a genome-wide association research approach (GWAS) to investigate the role of small nucleotide polymorphisms (SNPs) in genes related to hearing protection and determining whether these gene mutations lead to an increased sensitivity to hearing loss. In addition, I have been working on a project on the interactions between cancer cells and host stroma cells in melanoma tumor growth and development in a mouse model.

        My teaching responsibilities for the last 12 years were in HST 010 Functional Human Anatomy where I was the Acting Director of the course in 2011 and the Co-Director in 2012. I am now the Co-Director of the DSF course at UMass and teach in the Gross Anatomy lab.



        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Uribe PM, Mueller MA, Gleichman JS, Kramer MD, Wang Q, Sibrian-Vazquez M, Strongin RM, Steyger PS, Cotanche DA, Matsui JI. Dimethyl Sulfoxide (DMSO) Exacerbates Cisplatin-induced Sensory Hair Cell Death in Zebrafish (Danio rerio). PLoS One. 2013; 8(2):e55359.
          View in: PubMed
        2. Grondin Y, Cotanche DA, Manneberg O, Molina R, Treviño-Villarreal JH, Sepulveda R, Clifford R, Bortoni ME, Forsberg S, Labrecque B, Altshul L, Brain JD, Jackson RL, Rogers RA. Pulmonary delivery of d-methionine is associated with an increase in ALCAR and glutathione in cochlear fluids. Hear Res. 2013 Jan 4.
          View in: PubMed
        3. Treviño-Villarreal JH, Cotanche DA, Sepúlveda R, Bortoni ME, Manneberg O, Udagawa T, Rogers RA. Host-derived pericytes and Sca-1+ cells predominate in the MART-1- stroma fraction of experimentally induced melanoma. J Histochem Cytochem. 2011 Dec; 59(12):1060-75.
          View in: PubMed
        4. Cotanche DA, Kaiser CL. Hair cell fate decisions in cochlear development and regeneration. Hear Res. 2010 Jul; 266(1-2):18-25.
          View in: PubMed
        5. Kaiser CL, Kamien AJ, Shah PA, Chapman BJ, Cotanche DA. 5-Ethynyl-2'-deoxyuridine labeling detects proliferating cells in the regenerating avian cochlea. Laryngoscope. 2009 Sep; 119(9):1770-5.
          View in: PubMed
        6. Kaiser CL, Chapman BJ, Guidi JL, Terry CE, Mangiardi DA, Cotanche DA. Comparison of activated caspase detection methods in the gentamicin-treated chick cochlea. Hear Res. 2008 Jun; 240(1-2):1-11.
          View in: PubMed
        7. Cotanche DA. Genetic and pharmacological intervention for treatment/prevention of hearing loss. J Commun Disord. 2008 Sep-Oct; 41(5):421-43.
          View in: PubMed
        8. Spencer NJ, Cotanche DA, Klapperich CM. Peptide- and collagen-based hydrogel substrates for in vitro culture of chick cochleae. Biomaterials. 2008 Mar; 29(8):1028-42.
          View in: PubMed
        9. Parker MA, Corliss DA, Gray B, Anderson JK, Bobbin RP, Snyder EY, Cotanche DA. Neural stem cells injected into the sound-damaged cochlea migrate throughout the cochlea and express markers of hair cells, supporting cells, and spiral ganglion cells. Hear Res. 2007 Oct; 232(1-2):29-43.
          View in: PubMed
        10. Stone JS, Cotanche DA. Hair cell regeneration in the avian auditory epithelium. Int J Dev Biol. 2007; 51(6-7):633-47.
          View in: PubMed
        11. Duncan LJ, Mangiardi DA, Matsui JI, Anderson JK, McLaughlin-Williamson K, Cotanche DA. Differential expression of unconventional myosins in apoptotic and regenerating chick hair cells confirms two regeneration mechanisms. J Comp Neurol. 2006 Dec 10; 499(5):691-701.
          View in: PubMed
        12. Matsui JI, Parker MA, Ryals BM, Cotanche DA. Regeneration and replacement in the vertebrate inner ear. Drug Discov Today. 2005 Oct 1; 10(19):1307-12.
          View in: PubMed
        13. Parker MA, Anderson JK, Corliss DA, Abraria VE, Sidman RL, Park KI, Teng YD, Cotanche DA, Snyder EY. Expression profile of an operationally-defined neural stem cell clone. Exp Neurol. 2005 Aug; 194(2):320-32.
          View in: PubMed
        14. Roberson DW, Alosi JA, Cotanche DA. Direct transdifferentiation gives rise to the earliest new hair cells in regenerating avian auditory epithelium. J Neurosci Res. 2004 Nov 15; 78(4):461-71.
          View in: PubMed
        15. Morest DK, Cotanche DA. Regeneration of the inner ear as a model of neural plasticity. J Neurosci Res. 2004 Nov 15; 78(4):455-60.
          View in: PubMed
        16. Matsui JI, Cotanche DA. Sensory hair cell death and regeneration: two halves of the same equation. Curr Opin Otolaryngol Head Neck Surg. 2004 Oct; 12(5):418-25.
          View in: PubMed
        17. Wang H, Li J, Follett PL, Zhang Y, Cotanche DA, Jensen FE, Volpe JJ, Rosenberg PA. 12-Lipoxygenase plays a key role in cell death caused by glutathione depletion and arachidonic acid in rat oligodendrocytes. Eur J Neurosci. 2004 Oct; 20(8):2049-58.
          View in: PubMed
        18. Mangiardi DA, McLaughlin-Williamson K, May KE, Messana EP, Mountain DC, Cotanche DA. Progression of hair cell ejection and molecular markers of apoptosis in the avian cochlea following gentamicin treatment. J Comp Neurol. 2004 Jul 12; 475(1):1-18.
          View in: PubMed
        19. Parker MA, Cotanche DA. The potential use of stem cells for cochlear repair. Audiol Neurootol. 2004 Mar-Apr; 9(2):72-80.
          View in: PubMed
        20. Matsui JI, Haque A, Huss D, Messana EP, Alosi JA, Roberson DW, Cotanche DA, Dickman JD, Warchol ME. Caspase inhibitors promote vestibular hair cell survival and function after aminoglycoside treatment in vivo. J Neurosci. 2003 Jul 9; 23(14):6111-22.
          View in: PubMed
        21. Roberson DW, Alosi JA, Mercola M, Cotanche DA. REST mRNA expression in normal and regenerating avian auditory epithelium. Hear Res. 2002 Oct; 172(1-2):62-72.
          View in: PubMed
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