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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. 4th
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.
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