The candidate is a well-trained molecular biologist who is establishing an independent molecular nephrology research program working on the regulation and functions of hepatocyte growth factor (HGF) receptor (c- met) in the kidney. The immediate and long-term career goals of the candidate are to understand the potential role of HGF/c-met system in renal physiologic and pathophysiologic settings. During the award period, the candidate plans to acquire advanced knowledges and enhanced research skills in a timely fashion by participating in various workshops, to intellectually interact with senior investigators, and to supervise renal fellows and Ph.D students working in his lab, etc. Studies from the candidate's lab and others indicate that c-met transcription is a crucial event increasing HGF action and targeting it specifically to renal epithelial cells. Therefore, the overall goals of this proposal are to examine the molecular mechanism(s) governing c-met regulation and to investigate the biological effects of c-met/HGF in kidney cells. This will be accomplished by applying molecular and cellular biologic techniques in three specific aims.
In Aim 1, the c- met gene promoter region will be fully characterized by transfecting promoter-reporter gene constructs into renal epithelial cells, and by examining the DNA-protein interactions.
In Aim 2, the molecular mechanism(s) underlying ligand induced c-met expression will be investigated by transfecting reporter genes into renal epithelial cells and exposing them to HGF. DNA elements dictating c-met inducible expression will be analyzed by DNA-protein interaction and site-directed mutagenesis studies.
In Aim 3, the biological effects of HGF/c-met on renal epithelial cell injury and repair will be investigated by examining the role of HGF in protecting renal epithelial cell from apoptosis. These studies will provide important insights into the transcriptional regulation of c-met expression and its function in normal and diseased kidneys. Ultimately, these studies may suggest novel strategies to alter the course of human renal disease by regulating the HGF/c-met axis.
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