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KU Home  :  Pharmaceutical Chemistry  :  Pharmaceutical Chemistry - Faculty - Jennifer S. Laurence Ph.D.
Jennifer S.. Laurence Ph.D
Assistant Professor
Departments: Pharmaceutical Chemistry
Office: 2030 Becker Dr., MRB 320F
Email: laurencj@ku.edu
Phone: (785) 864-3405
Fax: (785) 864-5736

Educational Background:

Postdoctoral research, Biological Sciences, Purdue University, 2004
Ph.D., Chemistry, Purdue University, 2000
B.A., History, Miami University, 1994

Research Group:

  • Eric Carillo: Pharmacy Student
  • Natalie Ciaccio: Graduate Student
  • Sam Hinton: Undergraduate Student
  • Mary Krause: Graduate Student
  • Dana Leichty: Undergraduate Student
  • Talia Martin: Graduate Student
  • Krista Shipley: PhRMA Foundation Postdoctoral Research Fellow
  • Andria Skinner: Graduate Student
  • Robert Winefield: Postdoctoral Research Assistant

Research Interests:

Protein Structure and Function

Our lab utilizes a variety of biophysical techniques including high-field multidimensional solution NMR to determine structures and analyze dynamics of peripheral membrane proteins under various solution and environmental conditions. We examine the stability and dynamic motions of proteins and correlate these properties with efficiency of enzymatic function.

Structural studies have largely been carried out on globular proteins composed of regular secondary structure elements, and detailed information derived from these well-behaved macromolecules has contributed to our fundamental understanding of protein folds, enzyme catalysis and ligand binding. With the advent of high-throughput screening methods it has become apparent that numerous proteins involved in signal transduction have large segments that lack a globular fold, appearing disordered in the absence of their cellular context. These seemingly disordered regions interact with other proteins, nucleotides and membranes, transmitting vital information pertaining to all aspects of cell maintenance. In several proteins disorganized regions have been shown to develop specific structure in the context of binding partners. It is likely that common modes of binding exist and that new structural elements will be elucidated as these proteins are examined in the appropriate context. We are investigating the structural and functional changes that occur within proteins between the soluble and membrane bound states using a variety of biophysical, biochemical and analytical methods, including multidimensional NMR, analytical ultracentrifugation, CD and calorimetry.

We are also interested in defining fundamental principles involved in promoting catalysis within a protein. The complex chemical environment created by a folded polypeptide provides the opportunity to achieve high specificity in substrate selection and to accomplish unique, sophisticated chemistry. The features that support protein function are preserved during the course of evolution, and as a result, superfamilies of enzymes can contain sufficient diversity in their sequences to identify the base set of amino acids involved in catalysis. We are developing computational and statistical methods to predict which positions are conserved because of their structural or functional importance and verifying the results by assessing the effect these residues have on the enzyme’s catalytic activity and thermal stability. Our initial efforts are directed at examining the protein tyrosine phosphatase family, beginning with PRL-1.

Current Research Projects:

 
 

Natalie Ciaccio: Laurence Lab Group

See note regarding press release correction at bottom of the page
 
 

Publications:

Laurence, J. S., LiWang, A. C., and LiWang, P. J.: Effect of N-terminal Truncation and Solution Conditions on Chemokine Dimer Stability: Nuclear Magnetic Resonance Structural Analysis of Macrophage Inflammatory Protein -1b Mutants, Biochemistry 37: 9346-9354, 1998.

Laurence, J. S., Blanpain, C., Burgner, J. W., Parmentier, M., and LiWang, P. J.: CC Chemokine MIP-1b Can Function As a Monomer and Depends on Phe13 for Receptor Binding, Biochemistry 39: 3401-3409, 2000.

Laurence, J. S., Blanpain, C., De Leener, A., Parmentier, M., and LiWang, P. J.: Importance of Basic Residues and Quaternary Structure in the Function of MIP-1b: CCR5 Binding and Cell Surface Sugar Interactions, Biochemistry 40: 4990-4999, 2001.

Kim, S., Jao, S., Laurence, J. S., and LiWang, P. J.: Structural Comparison of Monomeric Variants of the Chemokine MIP-1b Having Differing Ability to Bind the Receptor CCR5, Biochemistry 40: 10782-10791, 2001.

Anderson, J.L., Frase, H., Laurence, J.S., Michaelis, S. and Hrycyna, C.A..: Molecular mechanisms of Ras isoprenylcysteine carboxyl methyltransferase (ICMT). Mol. Biol. Cell 13: 499A-499A, 2002.

Laurence, J. S., Hallenga, K. and Stauffacher, C. V.: 1H, 15N, 13C Resonance Assignment of the Human Protein Tyrosine Phosphatase PRL-1, J Biomol NMR 29: 417-418, 2004.

Zabell, K., Laurence, J.S., Kinch, M.S., Knapp, D.W. and Stauffacher, C.V.: Expression and purification of the intact cytoplasmic domain of the human receptor tyrosine kinase, EphA2, in E. coli, Protein Expression & Purification 47: 210-216, 2006. PMID: 16426859

Nonoyama, A., Laurence, J.S., Garriques, L., Qi, H., Le, T. and Middaugh, C.R.: A biophysical characterization of AC137 and evaluation of the empirical phase diagram using a peptide model, J. Pharm. Sci. 97: 2552-67, 2008. PMID: 17879973

Martin, A., David, V., Laurence, J.S., Schwarz, P.M., Lafer,E.M., Hedge, A.M. and Rowe, P.S.: Degradation of MEPE, DMP1 & release of SIBLING ASARM-peptides (minhibins): ASARM-peptide(s) are directly responsible for defective mineralization in HYP, Endocrinology 149: 1757-1772, 2008. PMID: 18162525

Skinner, A.L. and Laurence, J.S.: High-field Solution NMR Spectroscopy as a tool for Assessing Protein Interactions with Small Molecule Ligands, J. Pharm. Sci. 97: 4670-4695, 2008. PMID: 18351634

Ciaccio, N.A., Moreno, M.L., Bauer, R.L. and Laurence, J.S.: High-Yield Expression in E. coli and Refolding of the bZIP Domain of Activating Transcription Factor 5, Protein Expr. Purif. 62: 235-243, 2008. PMID: 18718539

Trivedi, M., Davis, R.A., Shabaik, Y., Roy, A., Verkhivker, G., Laurence, J.S., Middaugh, C.R. and Siahaan, T.J.: The role of covalent dimerization on the physical and chemical stability of the EC1 domain of human E-cadherin, J. Pharm. Sci., 2009 Feb 6. [Epub ahead of print]. PMID: 1919929

Trivedi, M., Laurence, J.S. and Siahaan, T.J.: The role of thiols and disulfides in protein structure and stability, Curr. Pept. Prot. Sci., in press.

Skinner, A.L. and Laurence, J.S.: 1H, 15N, 13C Resonance Assignment of the Reduced and Active form of Human Protein Tyrosine Phosphatase PRL-1, Biomol. NMR Assignments, in press.

Zheng, K., Laurence, J.S., Kuczera, K., Verkivker, G., Middaugh, R.C., Siahaan, T.J.: Characterization of multiple stable conformers of the EC5 domain of E-cadherin and the interaction of EC5 with E-cadherin peptides, Chem. Biol. Drug Design, in press.

Skinner, A.L., Vartia, A.A., Williams, T.D. and Laurence, J.S.: Determination of the reduction potential of the disulfide bond that controls enzymatic activity of phosphatase of regenerating liver PRL-1, Biochemistry, 2009 Apr 2, [E-pub ahead of print]. PMID: 19341304