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 Kirk Mykytyn, PhD
Assistant Professor
Departments of Pharmacology and Internal Medicine
Division of Human Genetics
5020 Graves Hall
333 W. 10th Avenue
Columbus, OH 43210
Phone: (614) 292-4985
mykytyn.1@osu.edu
Research Interests
My laboratory is interested in defining the roles of cilia-mediated signaling in development and disease. Our studies utilize mouse models of Bardet-Biedl syndrome, a human genetic disorder whose etiology has been linked to cilia function. These studies will provide insights into the functions of these understudied organelles and how ciliary dysfunction leads to complex diseases. Research Background Cilia and flagella are cellular appendages that are classified as either motile or primary. Motile cilia and flagella, such as sperm flagella and cilia lining the respiratory tract, are involved in generating flow or movement. Primary cilia are generally non-motile and provide important sensory and signaling functions. In mammals, primary cilia are present on almost all cell types, although their functions on most cells are unknown. Primary cilia have recently been implicated in the pathogenesis of many human disorders, including, polycystic kidney disease, retinal degeneration, sensorineural deafness and vestibular impairment, anosmia, and laterality defects. Bardet-Biedl syndrome (BBS) is a rare human genetic disorder characterized by obesity, pigmentary retinopathy, polydactyly, kidney and heart defects, hypogenitalism, and cognitive deficits. Patients with BBS are also at increased risk for diabetes mellitus and hypertension. BBS is a heterogeneous disorder and eleven causative genes have been identified. Although the precise functions of the BBS proteins remain unresolved, numerous studies in diverse model systems have established a convincing link between the BBS proteins and cilia function. Therefore, mouse models of BBS provide an excellent tool for determining the functions of the BBS proteins and exploring the roles of cilia in development and disease. Current Research We are exploring the functions of cilia and the BBS proteins both at the organismal and cellular level. In order to investigate the functions of the BBS proteins in ciliated cells we have developed systems for culturing ciliated primary renal epithelial cells and ciliated hippocampal neurons from wild-type and BBS animals. This approach allows us to determine the effects of lacking the BBS proteins at the cellular level and then investigate how that correlates with defects in development and disease pathogenesis. In fact, we have recently discovered that BBS mice have defects in the localization of neuronal ciliary receptors concomitant with defects in hippocampal development. This is a very exciting finding as it implicates for the first time neuronal ciliary signaling in neural development and may represent a new paradigm in the etiology of cognitive and neuropsychiatric disorders. Our long term research goals are to elucidate the roles of cilia in complex disorders, including obesity, diabetes, and hypertension. As we begin to understand the mechanisms of cilia function, their roles in the pathogenesis of complex diseases, and identify the proteins that are involved, it is my belief that this will lead to the identification of disease susceptibility genes and novel targets for future therapeutics. Education
PhD, Human Genetics, University of Utah, 1999
BS, Genetics, University of California (Davis), 1991
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