My lab is interested in understanding the genetic mechanisms underpinning the normal development and function of the ear, which mediates the sensations of hearing and balance. Dysfunction of the ear is a common congenital condition, affecting approximately 1 in 300 births, and many individuals born with normal hearing will subsequently develop age-related hearing loss caused by irreparable damage to auditory sensory cells. Our particular focus is on the roles and regulation of the genes coding for Fibroblast Growth Factor (FGF) signaling components in mouse ear development. These signals control many different aspects of ear development, including the initial induction, specification and shaping of the ear primoridium, as well as later processes of sensory and supporting cell differentiation. Indeed, mutations in FGF signaling components lead to hearing impairment in both mice and humans. Our mouse models of these conditions can help in devising therapeutic strategies.
A second focus of our research, which arose from studies of ear development in mice bearing mutations in Fgf3 and Fgf10, is heart development. Normal heart development is a complex process involving communication and coordination between cells that are located in different areas of the developing fetus. Congenital heart defects occur in approximately 1% of all births and many of the most common abnormalities are seen in mice with genetically engineered disturbances of FGF signaling pathways. We are determining exactly where specific FGFs are located, how these sites relate to cells that receive the signals, as well as exactly how, when, and where these signaling events affect cardiovascular development. Since the FGF signaling system is a potential drug target, developing an understanding of the details of the timing and quantitative nature of its contributions to cardiovascular development will be vital in devising effective therapies.