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Paul A. Watkins, M.D., Ph.D.
Kennedy Krieger Institute
707 N. Broadway
Baltimore, MD 21205
Phone: (443) 923-2754
Dr. Paul Watkins is a research scientist at the Kennedy Krieger Institute. He is also a professor of neurology at the Johns Hopkins University School of Medicine. He has held joint appointments in the Department of Biological Chemistry since 1992 and in the Center for Human Nutrition in the Department of International Health at the Johns Hopkins Bloomberg School of Public Health since 1994.
Dr. Watkins did his undergraduate, graduate and medical training at Johns Hopkins, receiving a medical degree and doctoral degree in biochemistry in 1978. In the years which followed, he served as both a research associate and medical staff fellow at the National Institutes of Health, as well as commissioned officer service for the United States Public Health Service.
Childhood X-linked adrenoleukodystrophy (ALD), which was depicted in the 1992 movie "Lorenzo’s oil," results from destruction of myelin in the brain. Biochemically, XALD patients are unable to break down fatty substances called very long-chain fatty acids (VLCFA). Because of this impairment, toxic VLCFA accumulate in the brain and other organs. A primary goal of the Watkins laboratory is to understand the biochemical basis of XALD and related genetic diseases. Patients with these diseases all have intellectual disabilities, adrenal gland insufficiency, and other significant health problems.
Research in the Watkins lab has focused on a family of enzymes involved in the metabolism of fatty acids, called "acyl-CoA synthetases." A subset of these enzymes that process VLCFA may contribute to the biochemical abnormalities in XALD. One enzyme, called ACSBG1, is of particular interest because fruit flies with a mutation in ACSBG1 resemble XALD by having brain degeneration and accumulation of VLCFA.
In the course of these studies, researchers in the Watkins Lab have discovered several new enzymes involved in VLCFA metabolism. One of these, which is not thought to be involved in XALD, was found at exceptionally high levels in brain tumors. When malignant brain tumor cells are depleted of this enzyme, the cells become significantly less malignant. Further investigation of this enzyme may yield new therapeutic approaches for brain tumors.
Pei Z., Fraisl P., Shi X., Gabrielson E., Forss-Petter S., Berger J. and Watkins P.A. (2013). Very long-chain acyl-CoA synthetase 3: Overexpression and growth dependence in lung cancer. PLoS One, 8(7). doi: 10.1371/journal.pone.0069392.
Nchoutmboube J.A., Viktorova E.G., Scott A.J., Ford L.A., Pei Z., Watkins P.A., Ernst R.K. and Belov G.A. (2013). Increased long chain acyl-CoA synthetase activity and fatty acid import is linked to membrane synthesis for development of picornavirus replication organelles. PLoS Pathogens, 9(6). doi: 10.1371/journal.ppat.1003401.
Montgomery C., Pei Z., Watkins P.A. and Miziorko H.M. (2012). Identification and characterization of an extramitochondrial human 3-hydroxy-3-methylglutaryl-CoA lyase. The Journal of Biological Chemistry, 287(40), 33227-33236.
Kadam S.D., Gucek M., Cole R.N., Watkins P.A. and Comi A.M. (2012). Cell proliferation and oxidative stress pathways are modified in fibroblasts from Sturge-Weber syndrome patients. Archives of Dermatological Research, 304(3), 229-235.
Watkins P.A. and Ellis J.M. (2012). Peroxisomal acyl-CoA synthetases. Biochimica et Biophysica Acta, 1822(9), 1411-1420.
Wang Y., Busin R., Reeves C., Bezman L., Raymond G., Toomer C.J., Watkins P.A., Snowden A., Moser A., Naidu S., Bibat G., Hewson S., Tam K., Clarke J.T.R., Charnas L., Stetten G., Karczeski B., Cutting G. and Steinberg S. (2011). X-linked adrenoleukodystrophy: ABCD1 de novo mutations and mosaicism. Molecular Genetics and Metabolism, 104(1-2), 160-166.
Melton E.M., Cerny R., Watkins P.A., DiRusso C.C. and Black P.N. (2011). Human fatty acid transport protein 2a/very Long Chain acyl CoA synthetase 1 (FATP2a/Acsvl1) has a preference in mediating the channeling of exogenous n-3 fatty acids into phosphatidylinositol. The Journal of Biological Chemistry, 286(35), 30670-30679.
He M., Pei Z., Mohsen A.W., Watkins P., Murdoch G., Van Veldhoven P.P., Ensenauer R. and Vockley J. (2011). Identification and characterization of new long chain acyl-CoA dehydrogenases. Molecular Genetics and Metabolism, 102(4), 418-429.
Moser A., Steinberg S.J., Watkins P.A., Moser H.W., Ramaswamy K., Siegmund K.D., Lee D.R., Ely J.J., Ryder O.A. and Hacia J.G. (2011). Human and great ape red blood cells differ in plasmalogen levels and composition. Lipids in Health and Disease, 10. doi:10.1186/1476-511X-10-101.