William A. Eaton, M.D., Ph.D., NIH Distinguished Investigator
- Chief, Laboratory of Chemical Physics, 1986-2021
- Scientific Director, Intramural AIDS Targeted Ant-viral Program (IATAP), 1986-2018
- Ph.D., University of Pennsylvania, 1967
- M.D., University of Pennsylvania, 1964
- B.A., University of Pennsylvania, 1959
The purpose of our research is to understand the physics of protein folding and to discover a drug for sickle cell disease.
Current research is focused entirely on pathophysiology and drug discovery for sickle cell disease, as well as monitoring ex-vivo sickling in sickle cell patients on drug trials, gene therapy trials, and natural history studies in collaboration with NHLBI and NIAID hematologists. A highly-sensitive, pathophysiologically-relevant and high throughput assays have been developed to screen compounds for ant-sickling activity. The assays use laser photolysis or nitrogen deoxygenation to induce sickling and automated image analysis to detect the formation of sickle fibers in individual red cells. As a strategy for the most rapid path to bringing a drug to market, the first phase of the screen is to test all U.S. Food and Drug Administration-approved drugs.
Applying our Research
Hydroxyurea is the only drug that is currently used to treat sickle cell disease, and helps, but does not cure, only about 50 percent of patients. Additional drugs are critically needed.
Need for Further Study
Further studies should look at making the connections among protein and mis-folding folding theory, experiments, and computer simulations. They should also look at the development of additional drugs for sickle cell disease.
- Treating sickle cell anemia.
- Tisdale JF, Thein SL, Eaton WA.
- Science (2020 Mar 13) 367:1198-1199. Abstract/Full Text
- Hemoglobin S polymerization and sickle cell disease: A retrospective on the occasion of the 70th anniversary of Pauling's Science paper.
- Eaton WA.
- Am J Hematol (2020 Feb) 95:205-211. Abstract/Full Text
Research in Plain Language
My research focuses on understanding the steps involved in protein folding — a process that transforms a string of amino acid molecules (protein building blocks) — into a complex, 3-dimensional structure that performs a biological function. This research uses rapidly pulsed laser light and fluorescent labeling of molecules to observe the steps in the protein folding process. My lab also uses laser techniques to search for a drug for the treatment of sickle cell disease.
- Abbreviated Curriculum Vitae of William A. Eaton (PDF, 8.56 KB)