Douglas A. Cotanche, Ph.D.
Douglas A. Cotanche, Ph.D.
Associate Professor, Department of Otolaryngology – Head & Neck Surgery, Boston University School of Medicine
Otolaryngology Research, Evans 637
Boston University Medical Campus
72 East Concord Street
Boston, MA 02118
Phone: (617) 638-2541
Fax: (617) 638-2546
The major focus of research in my laboratory over the last several years has been hair cell regeneration. I discovered in 1986 that the chicken cochlea is capable of producing new hair cells to replace those that were lost from noise exposure. This was quite a surprising finding because research at the time indicated that lost hair cells were irreplaceable and led to permanent hearing deficits. Since my initial findings, hair cell regeneration has become the focus of a number of major laboratories and has rapidly developed into an extremely exciting 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.
The current research projects in my laboratory are designed to address the mechanisms which 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. Normally, the sensory epithelium is composed of a postmitotic population of hair cells and supporting cells. Sound damage and aminoglycoside treatment are 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 goal is to identify the genes and proteins that regulate supporting cell proliferation and lead to the production of new hair cells.
We have also been exploring regeneration in the mammalian inner ear by transplanting neural stem cells into a gentamicin-damaged or sound-damaged guinea pig cochlea. Our experiments have shown that mouse neural stem cells will infiltrate the surviving cochlea, respond to local microenvironmental cues, and differentiate into neurons and glia within the spiral ganglion, as well as hair cells and supporting cells in the organ of Corti. We identified numerous cells in the spiral ganglion that were derived from the mouse stem cells but expressed genes particular to cochlear neurons or glial cells. A smaller number of stem cells migrated out to reach the organ of Corti where they differentiated into inner phalangeal cells, pillar cells, Deiters’ cells and outer hair cells. Since these stem cells positioned adjacent to one another within the organ of Corti or spiral ganglion could express different cell-specific genes, it suggests that the transplanted cells are able to recognize and respond to local signals within the cochlea and differentiate into a variety of cell types needed to repair the cochlear ganglion or sensory epithelium.
Although my laboratory is currently at Boston University School of Medicine, my teaching responsibilities remain at Harvard Medical School, where I participate in teaching HST 010, the Functional Human Anatomy class for first year medical students in the Harvard/MIT Division of Health Sciences and Technology.