Douglas A Cotanche PhD
Title Associate Professor
Institution University of Massachusetts Medical School
Department Cell and Developmental Biology
Address University of Massachusetts Medicial School
55 Lake Avenue North, S7-212
Worcester MA
Telephone 508/856-2261
Email
Narrative

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.

Publications
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. Dai CF, Mangiardi D, Cotanche DA, Steyger PS. Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo. Hear Res. 2006 Mar; 213(1-2):64-78.
  View in: PubMed
 
13. 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
 
14. 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
 
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. 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
 
17. 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
 
18. 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
 
19. 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
 
20. 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
 
21. 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
 
22. 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
 
23. Kenna MA, Wu BL, Cotanche DA, Korf BR, Rehm HL. Connexin 26 studies in patients with sensorineural hearing loss. Arch Otolaryngol Head Neck Surg. 2001 Sep; 127(9):1037-42.
  View in: PubMed
 
24. Roberson DW, Alosi JA, Messana EP, Cotanche DA. Effect of violation of the labyrinth on the sensory epithelium in the chick cochlea. Hear Res. 2000 Mar; 141(1-2):155-64.
  View in: PubMed
 
25. Roberson DW, Alosi JA, Messana EP, Nedder AP, Cotanche DA. Endotracheal isoflurane anesthesia for chick auditory surgery. Hear Res. 2000 Mar; 141(1-2):165-8.
  View in: PubMed
 
26. Cotanche DA. Structural recovery from sound and aminoglycoside damage in the avian cochlea. Audiol Neurootol. 1999 Nov-Dec; 4(6):271-85.
  View in: PubMed
 
27. Torchinsky C, Messana EP, Arsura M, Cotanche DA. Regulation of p27Kip1 during gentamicin mediated hair cell death. J Neurocytol. 1999 Oct-Nov; 28(10-11):913-24.
  View in: PubMed
 
28. Kruger RP, Goodyear RJ, Legan PK, Warchol ME, Raphael Y, Cotanche DA, Richardson GP. The supporting-cell antigen: a receptor-like protein tyrosine phosphatase expressed in the sensory epithelia of the avian inner ear. J Neurosci. 1999 Jun 15; 19(12):4815-27.
  View in: PubMed
 
29. Fernandes RP, Cotanche DA, Lennon-Hopkins K, Erkan F, Menko AS, Kukuruzinska MA. Differential expression of proliferative, cytoskeletal, and adhesive proteins during postnatal development of the hamster submandibular gland. Histochem Cell Biol. 1999 Feb; 111(2):153-62.
  View in: PubMed
 
30. Hennig AK, Cotanche DA. Regeneration of cochlear efferent nerve terminals after gentamycin damage. J Neurosci. 1998 May 1; 18(9):3282-96.
  View in: PubMed
 
31. Fernandes R, Fox M, Cotanche D, Lennon K, Kukuruzinska MA. Confocal imaging of gene expression during hamster submandibular gland biogenesis. Ann N Y Acad Sci. 1998 Apr 15; 842:212-6.
  View in: PubMed
 
32. Ofsie MS, Hennig AK, Messana EP, Cotanche DA. Sound damage and gentamicin treatment produce different patterns of damage to the efferent innervation of the chick cochlea. Hear Res. 1997 Nov; 113(1-2):207-23.
  View in: PubMed
 
33. Cotanche DA. Hair cell regeneration in the avian cochlea. Ann Otol Rhinol Laryngol Suppl. 1997 May; 168:9-15.
  View in: PubMed
 
34. Riedl AE, Lee KH, Moskalyk LA, Cotanche DA. The molecular biology of hair cell regeneration in the avian cochlea. Audiol Neurootol. 1997 Jan-Apr; 2(1-2):61-70.
  View in: PubMed
 
35. Ofsie MS, Cotanche DA. Distribution of nerve fibers in the basilar papilla of normal and sound-damaged chick cochleae. J Comp Neurol. 1996 Jul 1; 370(3):281-94.
  View in: PubMed
 
36. Lee KH, Cotanche DA. Potential role of bFGF and retinoic acid in the regeneration of chicken cochlear hair cells. Hear Res. 1996 May; 94(1-2):1-13.
  View in: PubMed
 
37. Lee KH, Cotanche DA. Localization of the hair-cell-specific protein fimbrin during regeneration in the chicken cochlea. Audiol Neurootol. 1996 Jan-Feb; 1(1):41-53.
  View in: PubMed
 
38. Janas JD, Cotanche DA, Rubel EW. Avian cochlear hair cell regeneration: stereological analyses of damage and recovery from a single high dose of gentamicin. Hear Res. 1995 Dec; 92(1-2):17-29.
  View in: PubMed
 
39. Cotanche DA, Messana EP, Ofsie MS. Migration of hyaline cells into the chick basilar papilla during severe noise damage. Hear Res. 1995 Nov; 91(1-2):148-59.
  View in: PubMed
 
40. Epstein JE, Cotanche DA. Secretion of a new basal layer of tectorial membrane following gentamicin-induced hair cell loss. Hear Res. 1995 Oct; 90(1-2):31-43.
  View in: PubMed
 
41. Lee KH, Cotanche DA. Detection of beta-actin mRNA by RT-PCR in normal and regenerating chicken cochleae. Hear Res. 1995 Jul; 87(1-2):9-15.
  View in: PubMed
 
42. Freeman DM, Cotanche DA, Ehsani F, Weiss TF. The osmotic response of the isolated tectorial membrane of the chick to isosmotic solutions: effect of Na+, K+, and Ca2+ concentration. Hear Res. 1994 Sep; 79(1-2):197-215.
  View in: PubMed
 
43. Cotanche DA, Lee KH. Regeneration of hair cells in the vestibulocochlear system of birds and mammals. Curr Opin Neurobiol. 1994 Aug; 4(4):509-14.
  View in: PubMed
 
44. Stone JS, Cotanche DA. Identification of the timing of S phase and the patterns of cell proliferation during hair cell regeneration in the chick cochlea. J Comp Neurol. 1994 Mar 1; 341(1):50-67.
  View in: PubMed
 
45. Cotanche DA, Lee KH, Stone JS, Picard DA. Hair cell regeneration in the bird cochlea following noise damage or ototoxic drug damage. Anat Embryol (Berl). 1994 Jan; 189(1):1-18.
  View in: PubMed
 
46. Cotanche DA, Henson MM, Henson OW. Contractile proteins in the hyaline cells of the chicken cochlea. J Comp Neurol. 1992 Oct 15; 324(3):353-64.
  View in: PubMed
 
47. Tilney LG, Cotanche DA, Tilney MS. Actin filaments, stereocilia and hair cells of the bird cochlea. VI. How the number and arrangement of stereocilia are determined. Development. 1992 Sep; 116(1):213-26.
  View in: PubMed
 
48. Stone JS, Cotanche DA. Synchronization of hair cell regeneration in the chick cochlea following noise damage. J Cell Sci. 1992 Aug; 102 ( Pt 4):671-80.
  View in: PubMed
 
49. Cotanche DA. Video-enhanced DIC images of the noise-damaged and regenerated chick tectorial membrane. Exp Neurol. 1992 Jan; 115(1):23-6.
  View in: PubMed
 
50. Stone JS, Cotanche DA. Hair cell differentiation in the developing chick cochlea and in embryonic cochlear organ culture. J Comp Neurol. 1991 Dec 15; 314(3):614-25.
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51. Cotanche DA, Corwin JT. Stereociliary bundles reorient during hair cell development and regeneration in the chick cochlea. Hear Res. 1991 Apr; 52(2):379-402.
  View in: PubMed
 
52. Cotanche DA, Petrell A, Picard DA. Structural reorganization of hair cells and supporting cells during noise damage, recovery and regeneration in the chick cochlea. Ciba Found Symp. 1991; 160:131-42; discussion 142-50.
  View in: PubMed
 
53. Shiel MJ, Cotanche DA. SEM analysis of the developing tectorial membrane in the chick cochlea. Hear Res. 1990 Aug 1; 47(1-2):147-57.
  View in: PubMed
 
54. Cotanche DA, Dopyera CE. Hair cell and supporting cell response to acoustic trauma in the chick cochlea. Hear Res. 1990 Jun; 46(1-2):29-40.
  View in: PubMed
 
55. Corwin JT, Cotanche DA. Development of location-specific hair cell stereocilia in denervated embryonic ears. J Comp Neurol. 1989 Oct 22; 288(4):529-37.
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56. Tilney MS, Tilney LG, Stephens RE, Merte C, Drenckhahn D, Cotanche DA, Bretscher A. Preliminary biochemical characterization of the stereocilia and cuticular plate of hair cells of the chick cochlea. J Cell Biol. 1989 Oct; 109(4 Pt 1):1711-23.
  View in: PubMed
 
57. Tilney LG, Tilney MS, Cotanche DA. New observations on the stereocilia of hair cells of the chick cochlea. Hear Res. 1988 Dec; 37(1):71-82.
  View in: PubMed
 
58. Corwin JT, Cotanche DA. Regeneration of sensory hair cells after acoustic trauma. Science. 1988 Jun 24; 240(4860):1772-4.
  View in: PubMed
 
59. Tilney LG, Tilney MS, Cotanche DA. Actin filaments, stereocilia, and hair cells of the bird cochlea. V. How the staircase pattern of stereociliary lengths is generated. J Cell Biol. 1988 Feb; 106(2):355-65.
  View in: PubMed
 
60. Schneider ME, Cotanche DA, Fambrough DM, Saunders JC, Matschinsky FM. Immunocytochemical and quantitative studies of Na+,K+-ATPase distribution in the developing chick cochlea. Hear Res. 1987 Nov; 31(1):39-53.
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61. Cotanche DA, Cotton CU, Gatzy JT, Sulik KK. Ultrastructural and electrophysiological maturation of the chick tegmentum vasculosum. Hear Res. 1987; 25(2-3):125-39.
  View in: PubMed
 
62. Cotanche DA, Saunders JC, Tilney LG. Hair cell damage produced by acoustic trauma in the chick cochlea. Hear Res. 1987; 25(2-3):267-86.
  View in: PubMed
 
63. Cotanche DA. Development of hair cell stereocilia in the avian cochlea. Hear Res. 1987; 28(1):35-44.
  View in: PubMed
 
64. Cotanche DA. Regeneration of hair cell stereociliary bundles in the chick cochlea following severe acoustic trauma. Hear Res. 1987; 30(2-3):181-95.
  View in: PubMed
 
65. Cotanche DA. Regeneration of the tectorial membrane in the chick cochlea following severe acoustic trauma. Hear Res. 1987; 30(2-3):197-206.
  View in: PubMed
 
66. Cotanche DA, Sulik KK. Parameters of growth in the embryonic and neonatal chick basilar papilla. Scan Electron Microsc. 1985; (Pt 1):407-17.
  View in: PubMed
 
67. Cotanche DA, Sulik KK. The development of stereociliary bundles in the cochlear duct of chick embryos. Brain Res. 1984 Nov; 318(2):181-93.
  View in: PubMed
 
68. Cotanche DA, Sulik KK. Early differentiation of hair cells in the embryonic chick basilar papilla. A preliminary report. Arch Otorhinolaryngol. 1983 Apr; 237(3):191-5.
  View in: PubMed
 
69. Cotanche DA, Sulik KK. Scanning electron microscopy of the developing chick tegmentum vasculosum. Scan Electron Microsc. 1982; (Pt 3):1283-94.
  View in: PubMed
 
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Keyword
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Keywords   
Hair Cells, Auditory
Cochlea
Regeneration
Chickens
Gentamicins
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Ward, Buffi
Yu, Hong

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