OHSU

David C. Dawson, Ph.D.

Email
dawsonda@ohsu.edu
Position
Professor and Chair of Physiology and Pharmacology
Primary Affiliation
SOM-Physiology & Pharmacology Department
Program Affiliation
Neuroscience Graduate Program
Physiology & Pharmacology
Program in Molecular & Cellular Biosciences

Summary of Current Research:

Structure and function of the CFTR Chloride Channel.

Dawson Lab: Searching for the cure for two lethal childhood diseases: Most people are surprised to learn that two devastating childhood diseases, cystic fibrosis and secretory diarrhea are closely linked. Cystic Fibrosis is the most common lethal genetic disease among Caucasians, affecting 1/2500 live births. Although the cystic fibrosis gene was identified nearly 20 years ago, a cure for the disease has remained elusive. Secretory diarrhea is an infectious disease that is the leading cause of infant death world-wide. A major world health problem, diarrheal disease causes billions of dollars of lost productivity in the U.S. alone. Both of these diseases are caused by abnormal regulation of the same molecule, a protein called CFTR that is found in cells of the human lung, pancreas, liver and GI tract. The protein functions as a gate (a chloride channel) which controls the movement of chloride ions out of cells. In cystic fibrosis genetic mutations alter the protein such that the channel is defective and chloride movement is reduced or absent. Reduced chloride movement in the cells of the lung produces thick, sticky mucus which becomes a breeding ground for bacteria and can cause a fatal plugging of the airways. In secretory diarrhea, like that produced by cholera, bacterial toxins alter cells of the intestine so that the CFTR gate cannot close. The resulting excessive chloride ion loss from the cells causes life-threatening loss of salt and water or dehydration. The goal of the research carried out in Dr. Dawson's lab is to provide the scientific basis for the development of drugs that can be used to treat these two lethal diseases of childhood. The research combines high-resolution electrophysiological measurements of CFTR's channel properties with chemical modification strategies designed to reveal what parts of the CFTR molecule are most important for its vital functions. This information is used to refine atomic-scale models for the protien. Understanding how this complex molecule does its job will provide the foundation for the design drugs or other therapies that can be used to increase the activity of CFTR in cystic fibrosis patients or to decrease the activity of CFTR in people suffering from secretory diarrhea.

Recent Publications

Dawson, D.C., Liu, X., Zhang, Z. and McCarty, N. “Anion Conduction by CFTR: Mechanisms and Models.” In: The Cystic Fibrosis Transmembrane Conductance Regulator. Kirk, K.L. and D.C. Dawson, editors, Landes Bioscience, Kluwer Academic/Plenum, 2003, pp 1-34.

Liu, X. L., Z. Zhang, J. Billingsly, N. McCarty and D.C. Dawson CFTR: a cysteine at position 338 in TM6 senses a positive electrostatic potential in the pore. Biophys J.;87(6):3826-41. 2004.

Zhang, Z-R., G. Cui, X. Liu, B. Song, D.C. Dawson and N.A. McCarty. Determination of the functional unit of the cystic fibrosis transmembrane conductance regulator chloride channel. One polypeptide forms one pore. J Biol Chem; 280(1):458-68. 2005.

Liu, X, C. Alexander, J. Serrano, E. Borg and D.C. Dawson. Variable reactivity of an engineered cysteine at position 338 in CFTR reflects different chemical states of the thiol. J.Biol. Chem. 281: 8275-8285, 2006.

Serrano, J.R., X. Liu, E.R. Borg, C.S. Alexander, C.F. Shaw and D.C. Dawson. CFTR: Ligand exchange between a permeant anion([Au(CN)2]-) and an engineered cysteine (T338C) blocks the pore. Biophysical Journal. 91: 1737-1748, 2006.

Education

  • B.S. Electrical Engineering ,University of Pittsburgh, 1966
  • Ph.D. Physiology, University of Pittsburgh, 1971
  • Postdoctoral, Yale University, 1971-73
  • Assistant/Associate Professor Physiology & Biophysics, University of Iowa 1973-1980
  • Associate Professor/Professor Physiology, University of Michigan 1980-1999

Non-Academic Interests

Hiking, Blues guitar, wine

Preceptor Rotations

Dr. Dawson has not indicated availability for preceptor rotations at this time.

Faculty Mentorship

Dr. Dawson has not indicated availability as a mentor at this time.