 | Paul A. Watkins, M.D., Ph.D Director of Lipid Enzymology Laboratory, Kennedy Krieger Institute 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, Department of International Health, at the Johns Hopkins Bloomberg School of Public Health since 1994. |
Biographical Sketch:
Dr. Watkins did his undergraduate, graduate and medical training at Johns Hopkins, receiving an MD and a PhD 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 Summary:
Childhood X-linked adrenoleukodystrophy (XALD), 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.
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.
Recent Publications/Presentations:
Watkins PA (2008) Very long-chain acyl-CoA synthetases. J. Biol. Chem. 283, 1773-1777.
Jia Z, Pei Z, Maiguel D, Toomer CJ, and Watkins PA (2007) The fatty acid transport protein (FATP) family: Very long-chain acyl-CoA synthetases or solute carriers? J. Mol. Neurosci. 33, 25-31.
Hamilton JA, Hillard CJ, Spector AA, and Watkins PA (2007) Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins: Application to Neurological Disorders. J. Mol. Neurosci. 33, 2-11.
Watkins PA, Maiguel D, and Jia Z (2007) Evidence for 26 distinct acyl-CoA synthetase genes in the human genome. J. Lipid Res. 48, 2736-2750.
Jia Z, Moulson CL, Pei Z, Miner JH, and Watkins PA (2007) FATP4 is the principal very long-chain fatty acyl-CoA synthetase in skin fibroblasts. J. Biol. Chem. 282, 20573-20583
Pei Z, Jia Z, and Watkins PA (2006) The second member of the human and murine “bubblegum” family is a testis- and brainstem-specific acyl-CoA synthetase. J. Biol. Chem. 281, 6632-6641.
Jia Z, Pei Z, Maiguel D, Toomer CJ, and Watkins PA (2007) The fatty acid transport protein (FATP) family: Very long-chain acyl-CoA synthetases or solute carriers? J. Mol. Neurosci. 33, 25-31.
Hamilton JA, Hillard CJ, Spector AA, and Watkins PA (2007) Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins: Application to Neurological Disorders. J. Mol. Neurosci. 33, 2-11.
Watkins PA, Maiguel D, and Jia Z (2007) Evidence for 26 distinct acyl-CoA synthetase genes in the human genome. J. Lipid Res. 48, 2736-2750.
Jia Z, Moulson CL, Pei Z, Miner JH, and Watkins PA (2007) FATP4 is the principal very long-chain fatty acyl-CoA synthetase in skin fibroblasts. J. Biol. Chem. 282, 20573-20583
Pei Z, Jia Z, and Watkins PA (2006) The second member of the human and murine “bubblegum” family is a testis- and brainstem-specific acyl-CoA synthetase. J. Biol. Chem. 281, 6632-6641.
Contact Information:
Paul A. Watkins, M.D., Ph.D.
Research Scientist
Kennedy Krieger Institute
707 North Broadway Baltimore MD 21205
(map & directions)
Telephone: (443) 923-2754
Facsimile: (443) 923-2755
Email:watkins@kennedykrieger.org
Professor of Neurology,
Johns Hopkins University School of Medicine
Johns Hopkins School of Public Health
Faculty | Clinical Programs | Research
Research Scientist
Kennedy Krieger Institute
707 North Broadway Baltimore MD 21205
(map & directions)
Telephone: (443) 923-2754
Facsimile: (443) 923-2755
Email:watkins@kennedykrieger.org
Professor of Neurology,
Johns Hopkins University School of Medicine
Johns Hopkins School of Public Health