Detailed Biography:

The molecular basis of development and disease of sensory organs My laboratory is primarily interested in the mechanisms controlling the development and homeostasis of the inner ear. The inner ear is a complex organ responsible for balance and sound detection in vertebrates. It originates as a neurectodermal placode shortly after gastrulation and, through an elaborated series of inductive events and combinatorial changes in gene expression, develops into the mature, functional organ. Our work follows two complementary research lines. Hair cell regeneration Hair cells are the inner ear mechanoreceptors for hearing and balance. Hair cells are highly susceptible to intense noise, ototoxic drugs and aging and their loss is the most common cause of deafness and equilibrium disorders in humans. In spite of recent advances the possibility of therapeutic hair cell regeneration in mammals is still unrealized. In order to improve our understanding of the molecular events underlying hair cell death and their regeneration from stem cells, we have developed an in vitro system of analysis. Neonatal mice sensory epithelia are cultured under controlled conditions and manipulated with a variety of genetic tools in order to induce transdifferentiation of putative pluripotent precursors into terminally differentiated hair cells. Genetic analysis of ear development. Our group is currently studying the genetic interactions between members of the Chd/BMP system of extracellular signals. BMPs are abundantly expressed in the developing inner ear and inactivation of Chd has shown that the correct functioning of the pathway is required for the proper development of the organ. Mouse mutants for different genes in this regulatory system are being analyzed for their effect on ear development. We are also screening for new genes active in ear development and homeostasis. Selected candidates are disrupted by targeted homologous recombination and the phenotypic consequences of their inactivation analyzed with molecular and physiological techniques.