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William A. Eaton, M.D., Ph.D., NIH Distinguished Investigator

Photo of William Eaton.
Scientific Focus Areas: Biomedical Engineering and Biophysics, Molecular Pharmacology, Clinical Research

Professional Experience

  • Chief, Laboratory of Chemical Physics, 1986-present
  • Scientific Director, Intramural AIDS Targeted Ant-viral Program (IATAP), 1986-Present
  • Ph.D., University of Pennsylvania, 1967
  • M.D., University of Pennsylvania, 1964
  • B.A., University of Pennsylvania, 1959

Research Goal

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

Current Research

Our current research is both basic and applied. Our basic research is concerned with fundamental aspects of the mechanism of protein folding. A series of novel techniques have been developed to study the dynamics of fast processes in protein folding. These include the use of nanosecond pulsed lasers to trigger and monitor the folding reaction, as well as single molecule fluorescence measurements. Simple theoretical models are used to interpret the experimental results and expose the basic underlying physics of these processes. The experimental results and theoretical modeling are providing critical benchmarks for the construction of a detailed picture of the sequence of events as a protein forms its native conformation from the random structures of the unfolded polypeptide chain.

Highly sensitive and pathophysiologically-relevant kinetic assays have been developed to screen compounds for ant-sickling activity. The assay uses 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

Understanding the physics of protein folding is essential for understanding protein mis-folding, the cause of many human diseases, including Alzheimer's disease, type II diabetes, and Parkinson's disease.

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.

Select Publications

Single-molecule fluorescence experiments determine protein folding transition path times.
Chung HS, McHale K, Louis JM, Eaton WA.
Science (2012 Feb 24) 335:981-4. Abstract/Full Text
Kinetic assay shows that increasing red cell volume could be a treatment for sickle cell disease.
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.
Proc Natl Acad Sci U S A (2017 Jan 31) 114:E689-E696. Abstract/Full Text
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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.

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