Faculty

Peying Fong Assistant Professor PhD, Physiology, University of California, San Francisco, 1989  Phone (785) 532-4524 e-mail pfong@vet.k-state.edu

Summary of Research Interests:

Our lab studies the regulation of sodium and chloride transport by epithelial cells, with a focus on the functional interactions between the epithelial sodium channel (ENaC) and the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). Understanding this regulation bears potentially high relevance to the collective understanding of the pathogenesis of cystic fibrosis (CF), polycystic kidney disease (PKD) and Pendred syndrome. Molecular, cellular, and tissue level approaches are utilized and the resultant information is integrated in order to address this overarching question.

Analysis of disease-associated ENaC subunit mutants: These studies entail the electrophysiological analysis of heterologously expressed mutant βENaC subunits previously found to be associated with CF-like disease (Sheridan et al, 2005). Wild-type and mutant cRNAs are expressed in the Xenopus laevis oocyte system and the resultant macroscopic currents measured by the two-microelectrode voltage clamp method. The lab uses biochemical analyses such as cell surface biotinylation and immunoprecipitation, as well as immunolocalization, to compare the activity of cellular level processes such as exocytosis and endocytosis. These combined methods allow us to distinguish between molecular and cellular level disruptions in producing the abnormal sodium currents associated with the expression of mutant βENaC.

An epithelial system to study regulation of ENaC by CFTR: The lab also uses thyroid epithelium as a model system to test the hypothesis that CFTR regulates the expression of ENaC by influencing endocytosis. Primary thyroid epithelial cultures express both ENaC and CFTR and are capable of bi-directional transport. Thus, this system is an excellent model for many of the tissues that are affected in CF. The experimental approach incorporates measurement of short-circuit current in the presence and absence of specific pharmacological interventions. These studies are complemented by endocytic uptake, cell surface biotinylation, and immunolocalization assays.

Thyroid transport mechanisms: In collaboration with Prof. Philine Wangemann, thyroid-specific ion transport mechanisms are being actively evaluated using a model organism for the human disease, Pendred syndrome--the Slc26a4 ^-/- mouse. These studies integrate both microarray and proteomic approaches in addition to classical electrophysiological and biochemical methods.

Selected publications:

de Andrade Pinto, A.C.O., Barbosa, C.M.L., Ornellas, D.S., Novaira, H.J., Souza-Menezes, J., Ortiga-Carvalho, T.M., Fong, P. and Morales, M.M. (2007) Thyroid hormones stimulate renal expression of CFTR. Cell Physiol. Biochem. 20: 83-90.

Gray, M.A. and Fong, P. (2007) Orchestration of epithelial chloride transport. In: M. Pusch, Volume Ed., E. Bittar, Series Ed., Advances in Molecular and Cell Biology: Chloride movements across cellular membranes, 38: 329-367, Elsevier, Inc.

Wang, Y.H., Guggino, W.B. and Fong, P. (2007) Anion Channels. In: Hebert, S. and Alpern, R., Eds., The Kidney: Physiology and Pathophysiology. 4^th Edition. Elsevier, Inc.

Ikeda, M., Fong, P., Boletta, A., Qian, F., Zhang, X.-M., Cheng, J., Cai, H., Germino, G.G. & Guggino, W.B. (2006) A regulatory role of polycystin-1 on cystic fibrosis transmembrane conductance regulator plasma membrane expression. Cell Physiol. Biochem. 18: 9-20.

Sheridan, M.B., Fong, P., Groman, J.D., Conrad, C., Flume, P., Diaz, R., Harris, C., Knowles, M. & Cutting, G.R. 2005. Mutations in the beta subunit of the epithelial Na+ channel in patients with a cystic fibrosis-like syndrome. Hum. Mol. Genet. 14: 3493-3498.

Fong, P. 2004. ClC-K channels: if the drug fits, use it. EMBO Rep. 5: 565-566.

Santos Ornellas, D., Grozovsky, R., Goldenberg, R.C., Carvalho, D.P., Fong, P., Guggino, W.B. & Morales, M.M. 2003. Thyroid hormone modulates ClC-2 chloride channel gene expression in rat renal proximal tubules. J. Endocrinology. 178: 503-511.

Fong, P., Argent, B.E., Guggino, W.B. & Gray, M.A. 2003. Characterization of vectorial chloride transport pathways in the human pancreatic duct adenocarcinoma cell line, HPAF. Am. J. Physiol. Cell. 285: C433-445.

Cooper, G.J. & Fong, P. 2003. Relationship between intracellular pH and chloride in Xenopus oocytes expressing the chloride channel, ClC-0. Am. J. Physiol. Cell: 284: C331-338.

Wills, N.K. and Fong, P. 2001. ClC chloride channels in epithelia: recent progress and remaining puzzles. News Physiol. Sci. 16: 161-166.