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School of Medicine
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Paul Allan Watkins, M.D., Ph.D.
Professor of Neurology
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.
- Research Scientist
- Professor of Neurology
- Joint Appointment in Biological Chemistry
- Professor of Oncology
Departments / Divisions
Centers & Institutes
- M.D., Johns Hopkins University School of Medicine (Maryland) (1978)
- Ph.D., Johns Hopkins University School of Medicine (Maryland) (1979)
Research & Publications
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.
Lab Website: Paul Watkins Laboratory
Selected PublicationsView all on Pubmed
Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease. Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, Sabbagh M, Honig LS, Porsteinsson AP, Ferris S, Reichert M, Ketter N, Nejadnik B, Guenzler V, Miloslavsky M, Wang D, Lu Y, Lull J, Tudor IC, Liu E, Grundman M, Yuen E, Black R, Brashear HR; Bapineuzumab 301 and 302 Clinical Trial Investigators. N Engl J Med. 2014 Jan 23;370(4):322-33. doi: 10.1056/NEJMoa1304839. PMID: 24450891
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.
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