Tzyh-Chang Hwang, Ph.D.

Professor HwangT@missouri.edu Visit Dr. Hwang's Lab Website

Research Interests

Cystic fibrosis, the most common lethal genetic disease in Caucasians, is caused by mutations that reduce chloride channel activity of the CFTR protein. The CFTR chloride channel is activated by protein kinase A (PKA)-dependent phosphorylation. ATP binding/ hydrolysis in two nucleotide binding domains (NBD1 and NBD2) of CFTRis coupled to the opening and closing of the phosphorylated channel. The most common CF- associated mutation, F508, causes an abnormal retention of the mutant protein in the endoplasmic reticulum. A small portion of F508 CFTR proteins can reach the plasma membrane and function as chloride channels. However, kinetic studies of these mutant CFTR channels in cell-attached patches indicate a lower
open probability in response to cAMP stimulation compared to the wild-type channels. Genistein, a plant isoflavone that is abundant in legumes, can dramatically enhance F508 CFTR channel currents activated via the cAMP pathway. This effect of genistein appears to be caused by a direct binding of genistein to the CFTR. Current studies are focused on understanding the molecular nature of genistein binding site(s) and on the kinetic mechanism of genistein's action. Our work on CFTR modulation could potentially provide information
useful for drug design and therapeutic intervention for cystic fibrosis.

Professional Background

• Received M.D. degree from the National Yang-Ming Medical College in Taiwan
• M.S. degree from the National Taiwan University
• Ph.D. degree in physiology from The Johns-Hopkins School of Medicine
• Completed postdoctoral training at The Rockefeller University
• Assistant professor in the Laboratory of Cardiac/Membrane Physiology at The Rockefeller University
• Joined Department in 1994
• Member of the Biophysical Society and the Society of General Physiologists
• Currently funded by the NIH and the Cystic Fibrosis Foundation

• 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 L. Clarke, Lara R. Gawenis, Tzyh-Chang Hwang, Nancy M. Walker, 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 (2004). Direct effects of 9-anthracene compounds on CFTR gating. 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.