Office Phone: 301-405-1812
Office Address: 4500
- A.B., Chemistry,1980, Barnard College, Columbia University
- Ph.D., Biochemistry, 1986, University of Illinois, Urbana-Champaign
- Postdoctoral Experience
- 1986-1987 Postdoctoral Fellow with Dr. Robert T. Sauer, Department of Biology, Massachusetts Institute of Technology
- 1987-1990 Postdoctoral Fellow with Dr. Gary K. Ackers Department of Biology, Johns Hopkins University
- 1990-1996, Assistant Professor, University of Maryland Baltimore County
- 1996-1999, Associate Professor, University of Maryland Baltimore County
- 1999-2002, Associate Professor, University of Maryland College Park
- 2002-present, Professor, University of Maryland College Park
Biophysical Chemistry, coupled equilibria in biological regulation, biotin distribution in humans, protein:protein
interactions, quantitative analysis of biological regulatory systems, allostery, thermodynamics and kinetics.
Major Recognitions and Honors
- NIH Postdoctoral Fellowship, 1987-1990
- DuPont Young Professor, 1993-1996
Significant Professional Service and Activities
- 1986-1989: NIH Postdoctoral Fellowship
- 1993-1996: DuPont Young Professorship, NIH-NIGMS, BBCA Panel-Member
- 2000-2004, F31/32 Panel Member, 2005, 2006, 2007, 2012, S10 Review Panel, August, 2006, August, 2007, MFSE (ad hoc) October, 2008, NSF-Major Research Instrumentation Panel-Member, 1997-1999, 2000 Preproposal Review Panel-Integrative Graduate Education and Research Training (IGERT) Program 1999, 2002, 2009, GEX Panel Member, April 2011, November, 2011, Ad-Hoc reviewer for individual proposals.
- Biophysical Society: Council: 2000-2003 (elected position, Executive Board: 2001-2003, Annual Meeting Program Committee: 2000-2003, Elected Chair, Molecular Biophysics Subgroup:2001-2002, Chair, Nominations Committee: 2003-2004, Member, 2004-2005, 50th Anniversary Meeting Committee Member: 2003-2006, Secretary of the Biophysical Society, Term-2007-2011,
- President, Gibbs Conference on Biothermodynamics: 2005-2006, Co-Chair (with Michael Hecht) 2010 Biopolymers Gordon Research Conference
- Associate Editor-Protein Science 2009-present,
- Editorial Advisory Board Member-Biochemistry, 2010-present
Regulation of protein function in complex biological circuitry, allostery, thermodynamics, kinetics, modeling
Synthesize the information obtained from multiple approaches to elucidate mechanisms of regulation of protein function and relate this understanding to biology.
Biotin plays a critical role in metabolism in all organisms and elaborate systems have evolved to regulate its homeostasis. We use the E. coli and human systems to investigate mechanisms of regulation of protein function.
I. Modeling the E. Coli Biotin Regulatory System
The biological circuit, outlined in the figure to the right, functions both in funneling the vitamin, biotin, into fatty acid synthesis and in regulating its biosynthesis. The central protein of the circuit, BirA, catalyzes covalent attachment of biotin to BCCP, a subunit of the biotin-dependent enzyme, acetyl CoA carboxylase and binds sequence-specifically to the operator (bioO) of the biotin biosynthetic operon to repress transcription initiation, thereby regulating intracellular biotin concentration. We have developed an equilibrium thermodynamic model for this regulatory system and are testing the model in the test tube and the cell.
II. Surface Loops in Evolution of Protein Function
The ability of BirA to carry out its two distinct functions reflects the use of multiple flexible surface loops (colored segments). Although functionally conserved, in microbial BirA proteins the loop sequences are heterogeneous. We employ combined molecular biology, biophysical measurements and structural studies to elucidate the relationship of this loop sequence heterogeneity to their conserved functional roles in BirA proteins.
III. Human Biotin Distribution
Humans obtain biotin from dietary protein or intenstinal bacteria, which is then distributed to the five biotin-dependent carboxylases in a reaction catalyzed by holocarboxylase synthetase (HCS). Measurements of the kinetics of biotin transfer to the carboxylases indicates a 100-fold range in the the rates. We are studying the structural and dynamic basis of this kinetic discrimination, which contributes to regulating important metabolic processes including gluconeogenesis, amino acid catabolism and fatty acid synthesis and oxidation.