William A. Eaton, M.D., Ph.D.

NIH Distinguished Investigator

Laboratory of Chemical Physics

NIDDK

Building 5, Room 104
5 Memorial Dr
Bethesda, MD 20814

+1 301 496 6030

eaton@niddk.nih.gov

Research Topics

The purpose of our research is to understand the physics of protein folding and to discover a drug for sickle cell disease.

Current Research

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.

Biography

  • Chief, Laboratory of Chemical Physics, 1986-present
  • 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

Selected Publications

  1. Tisdale JF, Thein SL, Eaton WA. Treating sickle cell anemia. Science. 2020;367(6483):1198-1199.

  2. Eaton WA. Hemoglobin S polymerization and sickle cell disease: A retrospective on the occasion of the 70th anniversary of Pauling's Science paper. Am J Hematol. 2020;95(2):205-211.

  3. Li Q, Henry ER, Hofrichter J, Smith JF, Cellmer T, Dunkelberger EB, Metaferia BB, Jones-Straehle S, Boutom S, Christoph GW, Wakefield TH, Link ME, Staton D, Vass ER, Miller JL, Hsieh MM, Tisdale JF, Eaton WA. Kinetic assay shows that increasing red cell volume could be a treatment for sickle cell disease. Proc Natl Acad Sci U S A. 2017;114(5):E689-E696.

  4. Eaton WA, Bunn HF. Treating sickle cell disease by targeting HbS polymerization. Blood. 2017;129(20):2719-2726.

  5. Eaton WA. Linus Pauling and sickle cell disease. Biophys Chem. 2003;100(1-3):109-16.


This page was last updated on October 15th, 2020