Quinton Lab Members: (left or right) Guillermo Flores, Ruth Muchekehu, MM Reddy, Kirk Taylor, AK Shamshuddin, Paul Quinton, Joanne Albrecht, Abi Garcia, Jessie Yang, Kevin Shaw (not shown)
Our work has focused almost exclusively on intact, native tissues. Using single, isolated, microperfused human sweat ducts, we discovered defective anion (Cl-) conductance as the basic functional defect in this hereditary disease CF. We pursued this work with numerous studies of the properties of the affected anion channel protein (CFTR) mainly in sweat gland tissue, demonstrating roles for ATP, cAMP, kinase, phosphatase, glutamate, intracellular pH and ion concentrations in regulating CFTR function. We introduced the concept that this defective anion conductance is the basis of the characteristically pathogenic increase in mucus viscosity (mucoviscidosis) in CF target organs. That is, our lab discovered and showed that mucins are critically dependent on concurrent HCO3- secretion through CFTR to form normal mucus. More recently, we hypothesized and demonstrated that a previously unknown structure/function arrangement in the plications of the epithelial lining of pulmonary airways permits simultaneous secretion and absorption of surface liquid that is essential for lubricating and cleaning these vital respiratory components. We validated these properties in human airways. We also introduced two novel diagnostic biomarkers based on abnormal CF sweating functions and composition that reflect defective CFTR function in both, Cl- and HCO3- secretory and absorptive transport. We are evaluating the direct effects of small solute drugs on CFTR function in intact native sweat glands and small airways.