Research Interests
We study the functional mechanisms and role in health and disease of multisubunit proteins involved in nitrogen metabolism. Binding of ligands typically causes changes in tertiary structure and subunit interactions that mediate and regulate their biological activity. We use X-ray crystallography, computer modeling and genetic, physical biochemical and enzymological approaches to understand the relationship between structure and function and to determine how naturally mutations alter function and cause disease. Current research focuses on enzymes of the urea cycle in humans and arginine biosynthesis in micro-organisms and plants. Mutations in these enzymes often cause clinical hyperammonemia resulting in neurological symptoms or even death. In collaboration with Dr. Mendel Tuchman and his colleagues at Children’s National Medical Center in Washington, DC, we have focused on ornithine transcarbamlyase (OTCase) and N-acetyl-L-glutamate synthase (NAGS). We also discovered novel biochemical pathways for arginine biosynthesis in bacteria and characterized the enzymes involved both biochemically and structurally. Current research focuses on the mechanism by which NAGS acts as a master regulator of the urea cycle and the development of new treatments for treating disorders of the urea cycle.
Awards
- Fellow, American Association for the Advancement of Science, 1985
- NIH MERIT Award, 1991
- Emily M. Gray Award for Education, Biophysical Society, 2002
- Doctor Scientiae, McMaster University, 2007
Previous Positions
- Polytechnic Institute of Brooklyn, Assistant Professor, 1970-1973
- Wesleyan University, Department of Biology, 1970-1984; Department of Molecular Biology and Biochemistry, 1984-1991
- Instructor, Physiology course, Marine Biological Laboratories, Woods Hole, MA, summers of 1981-83
- University of Minnesota, Department of Biochemistry: Professor, 1991-1998; Head, 1991-95
- University of Maryland, Dean of Chemical and Life Sciences and Professor of Chemistry and Biochemistry, 2000-2010
Major National Service
- President, Biophysical Society, 1993-4
- Advisory Board, Protein Data Bank, Brookhaven National Laboratories, 1994-99; Chair,1997-98
- U.S. National Committee for the International Union of Pure and Applied Biophysics,1995-99
- National Research Council Space Studies Board Committee on Space Biology and Medicine,1995-2000
- Board of Directors, Federation of American Societies for Experimental Biology, 1993-94; 2004-06 Biological Sciences Advisory Committee, NSF, 2003-06
- Biological Sciences Advisory Committee, NSF, 2003-06
- Journal of Biological Chemistry, Editorial Board, 1995-2000; Associate Editor, 2002-present
- Board of Scientific Counselors, National Center for Biotechnology Information, National Library of Medicine, 2008-13
- Jefferson Science Fellow, US Department of State, 2011-12
Education
- B. Sc. (Hon), Biochemistry, McMaster University, 1965
- Ph.D., Molecular Biophysics, Yale University, 1969
- NIH NRSA fellow, Biophysical Chemistry, Yale University, 1969-70
