Lane L. Clarke, PhD, DVM
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University of Missouri – Columbia (MU)
The laboratory investigates acid-base transporter dysfunction in cystic fibrosis (CF) and other genetic diseases as it relates to intestinal stem cell biology (ISCs) and differentiation of secretory cells. In vivo studies use transgenic mice with alterations of CFTR (the cystic fibrosis gene) or other acid-base transporters. In vitro studies use regenerating murine or human primary intestinal organoids grown in 3D gel culture. Transporter activity is measured by fluorescence confocal microscopy and electrophysiology. Gene expression is measured using quantitative PCR, immunoblots and immunofluorescence. Current projects investigate 1) the role of CFTR, a chloride and bicarbonate channel, in down-regulating cell cycle dynamics and Wnt/?-catenin signaling in ISCs, and the consequences of CFTR loss on intestinal hyperproliferation/cancer in CF; 2) mechanisms of intracellular pH (pHi) regulation in ISCs and its manipulation to offset ISC damage resulting from chemotherapy; and 3) pathological mechanisms causing dysfunction of mucus secreting goblet cells in the CF intestine.