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Tzyh-Chang Hwang, PhD

Professor, Department of Medical Pharmacology and Physiology
Office Location: 222C DCRC
Office Phone: 573-882-2181
HwangT@missouri.edu

Research Interests

Structure-function studies of CFTR chloride channel

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:

  • How are the channels modulated by phosphorylation at multiple consensus serine residues?
  • What are the phosphatases involved?
  • How is the disease-associated mutant CFTR affected? How can we amend the defect?
  • How is the energy of ATP hydrolysis harvested and transduced to protein conformational changes in CFTR gating?
  • What are the structural changes in CFTR gating?
  • What are the functional roles of NBD1 and NBD2 in controlling CFTR gating?

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


Published by Dalton Cardiovascular Research Center, 134 Research Park Dr., Columbia, MO 65211
Phone: 573-882-7588 | Fax: 573-884-4232 | Email: dalton@missouri.edu