Causes of sensory hair cell death: mechanisms of homeostasis, environmental stress and cellular repair involving the cell cycle, DNA damage and DNA repair
The goal of this project is to understand the basis for the lifelong homeostatic maintenance of permanently postmitotic cells in the nervous system, including the inner ear. Sensory hair cells, like most neurons, stop dividing either in the embryo or shortly after birth. If lost due to environmental stress (such as loud noise, chemotherapy agents, certain antibiotics or aging), these cells do not regenerate. This means that lifelong cell renewal/ repair must occur in the absence of cell replacement and in the presence of strong control over cell division. These factors are associated with a heightened sensitivity to physiological/ environmental stress. Our focus is on how the cell cycle machinery in hair cells contributes to their sensitivity to stress, and how these pathways interact with other homeostatic pathways, such as those involved in DNA damage and repair. Currently, we are studying mouse models of the human DNA repair disorder Cockayne Syndrome, which is associated with aspects of premature aging and, as our current research indicates, sensory-neural hearing loss.