Tzyh-Chang Hwang, PhD
Professor, Department of Medical Pharmacology and PhysiologyOffice Location: 222C Dalton Cardiovascular Research Center
Office Phone: 573-882-2181
HwangT@missouri.edu
Research Interests
Research Description
The main focus of Hwang's research is on electrophysiological studies of the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) chloride channel. Cystic fibrosis (CF) is the most common lethal genetic disease in the United States. Defects in the CFTR chloride channel in patients with CF result in dehydrated viscous mucus in the airway believed responsible for the most severe symptoms of the disease. To date, more than 800 different mutations have been identified as disease-associated, but the most prevalent mutation is the deletion of a single amino acid, phenylalanine 508 (Delta F508). It is well established that two ATP-dependent processes are involved for normal CFTR function. First, the channel has to be phosphorylated by the cAMP-dependent protein kinase (PKA). Second, ATP hydrolysis by the nucleotide binding domains (NBD1 and NBD2) controls the opening and closing of PKA-phosphorylated CFTR channels. Hwang's recent work has indicated that the phosphorylation activation step is rate-limiting for CFTR function in an intact cell and that a slow phosphorylation or/and a faster dephosphorylation of Delta F508-CFTR results in an abnormal response of this mutant channel to cAMP stimulation. This abnormality may contribute to the pathophysiology of CF. Using a combination of molecular biological, biochemical and electrophysiological techniques, future research is aimed at tackling the following questions: Working together with a team of CF investigators, Hwang anticipates future application of the bench-side, basic science results to the clinical therapeutics in CF.
Professional Background
- Obtained MD degree from the National Yang-Ming Medical College, Taiwan.
- Obtained MS, National Taiwan University.
- Obtained PhD in physiology from Johns-Hopkins School of Medicine.
- Completed postdoctoral training at Rockefeller University.
- Served as assistant professor in the Laboratory of Cardiac/Membrane Physiology, Rockefeller University.
- Member of the Biophysical Society
- Curently funded by the National Institutes of Health (NIH) and the Cystic Fibrosis Foundation.
Selected Publications
- Tzyh-Chang Hwang, Roger Koeppe, II. and Olaf Andersen (2003). Genistein can modulate channel function by a phosphorylation-independent mechanism: Importance of bilayer mechanics and hydrophobic mismatch. Biochemistry 42:13646-13658.
- Tomohiko Ai, Silvia Bompadre, Xiaohui Wang, Shenghui Hu, Min Li, and Tzyh-Chang Hwang (2004). Capsaicin potentiates wild-type and mutant CFTR chloride channel currents. Molecular Pharmacology 65:1415-1426.
- Lane Darren B. Gruis and Elmer M. Price. (2004). A Domain Mimic Increases {Delta}F508 CFTR Trafficking and Restores cAMP-Stimulated Anion Secretion in Cystic Fibrosis Epithelia. Am. J. Physiol. 287:C192-199.
- Tomohiko Ai, Silvia Bompadre, Yoshiro Sohma, Min Li and Tzyh-Chang Hwang (200). Pflügers Arch. 449:88-95.
- Silvia G. Bompadre, Tomohiko Ai, Jeong Han Cho, Xiaohui Wang, Yoshiro Sohma, Min Li, and Tzyh-Chang Hwang. (2005). CFTR gating I: Characterization of the ATP-dependent gating of a phosphorylation-independent CFTR channel (DR-CFTR). J. Gen. Physiol. 125:361-375.
- Silvia G. Bompadre, Jeong Han Cho, Xiaohui Wang, Xiaoqin Zou, Yoshiro Sohma, Min Li, and Tzyh-Chang Hwang. (2005). CFTR gating II: Effects of nucleotide binding on the stability of open states. J. Gen. Physiol. 125:377-394.