Stefan Heller
Research Interests
Current Lines of Research:
All hearing sensation is derived from the electrical output of a remarkably small number of sensory cells: fewer that 15,000 per cochlea. These hair cells are the mechanoelectrical transducers of the inner ear: deflections of the stereociliary bundles on their apical surfaces lead to transmitter release from their basolateral poles, leading, in turn, to signal generation in the peripheral axons of the auditory nerve fibers.
Most types of congenital and acquired hearing loss arise from loss of these sensory cells. The incidence of heritable deafness is high: one child in a thousand is born deaf; another one in a thousand becomes deaf before adulthood. The prevalence of acquired hearing loss is rising, as the population ages, and as noise pollution steadily increases. It is estimated that one in three adults over the age of 65 has a handicapping hearing loss.
Underlying the irreversibility of hearing loss in mammals is the incapacity to replace lost hair cells by cell division or by regeneration from endogenous cells in the inner ear epithelia. Hair cell replacement, either by stimulation of regeneration (as occurs naturally in non-mammalian vertebrates) or by transplantation of progenitor cells capable of differentiating into hair cells, remains therefore the ultimate goal in the development of treatment applications to reconstruct the damaged inner ear.
Our recent work has focused on creating inner ear cell types, in particular hair cells and auditory neurons, from a renewable source. We have shown that embryonic stem (ES) cells and somatic inner ear stem cells can serve as such a source. The ongoing research in my laboratory is focusing on defining and exploring signaling pathways that control hair cell and auditory neuronal generation in vitro and in vivo toward a better understanding of native inner ear development and, ultimately, to develop cell- or drug-based therapies for inner ear disorders.
A second emerging line of research focuses on functional characterization of genes and proteins that are involved in hair cell mechanotransduction or stereociliary function. The long-term goal of this research is to unravel the structure and function of the mechanoelectrical transduction machinery, a multi-protein complex located at the tips of stereocilia. This research involves molecular, biochemical, and biophysical approaches as well as structural biology.
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