Karen Steel

Karen Steel’s primary research interest is the genetics of deafness, using mouse mutants to gain access to the molecules involved in normal development and function. She has focussed on identifying genes underlying deafness and understanding the molecular and physiological basis for the dysfunction. Her group, together with many collaborators, has published phenotypic descriptions of over 80 different mouse mutants representing 36 loci, and they have identified 38 mutations in 22 different genes by positional cloning. For several of these, she has collaborated with human geneticists to identify mutations in the same genes in humans with deafness. Analysis of these new mouse mutants showed that a very wide range of mechanisms can cause deafness, including middle ear malformations, middle ear inflammation, inner ear malformation, sensory hair cell developmental defects, homeostatic failure, and stalled maturation.

Despite the common assumption that hearing loss is due to sensory hair cell degeneration, analysis of this large panel of mutants shows that degeneration is an epiphenomenon, not a primary cause of deafness. Each new mutation and gene identified adds valuable information about critical processes in the auditory system, but it is likely that there will be over 500 genes required for normal hearing and identifying these is a key first step in constructing the molecular pathways and networks involved. For this reason, gene discovery remains a core goal of the research. Progressive loss of auditory function with age is a major problem in the human population. Hearing loss is profoundly isolating, both socially and economically, and has a major impact on the quality of life of those affected. The current research in Karen Steel’s laboratory aims to understand the reasons for age-related decline in auditory function using mouse models with progressive loss of hearing ability.