Soundarapandian Vijayakumar, Ph.D.

ARPKD is a rare but severe hereditary disease associated with a high perinatal mortality. Using PCK rat that harbors a spontaneous splicing mutation in the PKHD1 gene and exhibits many characteristics of human ARPKD as our model system, we are investigating the molecular mechanisms that regulate ARPKD cystogenesis. In particular we are interested in identifying novel proteins that interact with fibrocystin and identifying novel therapeutic agents that could inhibit cyst growth. We utilize microarray, real-time PCR, confocal microscopy, flow sorting and organ culture techniques in addition to standard biochemical and cell biological tools.

2. Mechanisms that regulate kidney intercalated cell differentiation and adaptation

Metabolic acidosis is a clinical disturbance characterized by an increase in blood plasma acidity and can lead to major cardiovascular, respiratory and skeletal abnormalities. Normal kidneys respond to metabolic acidosis by reversing their proton pumping activity and bicarbonate flux with the help of A-type and B-type intercalated cells of the kidney. We discovered that a novel 230kD extracellular matrix protein, hensin mediates this regulation by remodeling the intercalated cells. Hensin is a multifunctional protein and its orthologs DMBT1 and Gp-340 have been implicated in tumor suppression and innate immunity respectively. We are currently investigating (A) the role of galectin-3 in ECM assembly of hensin (B) the role of peptidyl prolyl isomerases in hensin folding and (C) signaling mechanisms regulated by hensin that lead to epithelial remodeling. We are using cell culture and knock-out mice models in these studies. The long term objective is to identify mechanisms that lead to differentiation of intercalated cells. An active collaboration with Schwartz Lab is ongoing.

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