Professor of Physiology and Biophysics; Professor of Medicine
Gastroenterology; Ion channel kinetics and structure; Membrane Transport (Ion Transport); Molecular and Cellular Biology
Research in my laboratory concerns neurotransmitter and hormone-mediated anion secretion by gastrointestinal secretory tissues like intestinal crypts and liver ducts. I am determining the mechanisms that regulate the basolateral membrane K+ channel, KCNQ1, in anion secretion because these channels play a critical role in secretion by maintaining membrane potential as a driving force for anion exit across the apical cell membrane. Characterization of KCNQ1 K+ channels will help us to understand and remedy defects in anion secretion, especially in diseases like cystic fibrosis. I use electrophysiological techniques, including Ussing chamber, patch-clamp, and Fura-2 fluorescence techniques. I am also studying the mechanisms by which K+ channel antagonists (e.g., Zn2+) block KCNQ1 channels so that anti-secretory, anti-diarrheal drugs can be developed. I have past experience determining the mechanisms by which neurotransmitters regulate K+ channels via inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release transduction pathways. I am also collaborating with Dr. John Crane to define the mechanisms by which Zn2+ inhibits the effects of Enteropathogenic E. coli (EPEC) on epithelial cell death and EPEC-stimulated phosphorylation and activation of the CFTR Cl- channel.
There is considerable controversy concerning the role and basis of GI disorders associated with autism. In collaboration with Drs. Randall Rasmusson and Glenna Bett, I am investigating the mechanistic link between autism susceptibility and abnormal GI function. I propose that disorders of cellular Ca2+ homeostasis play a key role in the GI disorders of autism. Using mouse models derived from Cav1.2 Ca2+ channel defect that produces the human disorder, Timothy Syndrome, I am characterizing muscle tension and electrophysiological properties of the Ca2+ channel in intestinal smooth muscle. This information will lead to new approaches to identify therapeutic targets and treatments for autistic spectrum GI disorders and symptoms.