Douglas A. Cotanche, PhD
Associate Professor of
Otology and Laryngology
Harvard Medical School/Children's Hospital

MRRC Project(s)

R01 DC01689-10
Cell Form and Gene Expression in Hair Cell Regeneration

Deafness in children is most frequently caused by sensorineural hearing loss (SNHL), i.e. the loss of the sensory hair cells that transduce sounds into neural signals. SNHL is caused by many known factors, such as genetic mutations, viral or bacterial infections, traumatic injury, and immunologic responses. However, there are many cases (25-50%) for which no known cause can be identified, although the continuing discovery of new genetic causes for SNHL is gradually reducing that percentage. The reason for the profound deleterious effect of SNHL is that in mammals the hair cells are created only during embryogenesis and if hair cells are lost after birth, they cannot be replaced.

Work in my laboratory in the mid-1980’s demonstrated that bird cochleas have the capacity to regenerate hair cells after sound damage or aminoglycoside treatment. We were able to determine that when hair cells are lost from the cochlea, the surviving supporting cells re-enter a proliferative state and generate new cells that can differentiate as hair cells and restore auditory function. Our work in the last five years has concentrated on identifying the cellular and molecular events that control cell death in the hair cells, induce proliferation in the supporting cells, control the differentiation and maturation of new hair cells, and reestablish connections with the cochlear innervation. Our ultimate goal with this work on hair cell regeneration in the avian ear is to employ the mechanisms we identify to induce or regulate hair cell regeneration in the mammalian, and eventually the human, cochlea.