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Chemistry

Paul Thompson, Ph.D.

Associate Professor
Department of Chemistry
Florida Campus
Laboratory Website
pthompso@scripps.edu
(561) 228-2860

Scripps Research Joint Appointments

Faculty, Graduate Program

Research Focus

The Thompson laboratory uses the techniques of chemical biology, biochemistry, and enzymology to develop inhibitors/drugs targeting disease associated enzymes as well as developing novel diagnostics for cancer. Currently, our major research foci are: 1) Developing inhibitors and probes targeting the Protein Arginine Deiminases, a class of enzymes whose activity is dysregulated in multiple human diseases including, Rheumatoid Arthritis, Colitis, Spinal Regeneration, and Cancer. 2) Developing inhibitors and probes targeting the Protein Arginine Methyltransferases, a class of enzymes whose activity is dysregulated in heart disease and cancer. 3) Developing inhibitors targeting the Protein Adenylyltransferases. These enzymes are present in pathogenic bacteria and are potential targets for the development of novel antibiotics. 4) Developing synthetic lectins that can be used for the early diagnosis and treatment of cancer.

Education

B.S., Biochemistry, McMaster University, 1994
Ph.D., Biochemistry, McMaster University, 2000

Professional Experience

2010-present Associate Professor with tenure, The Scripps Research Institute, Scripps Florida, Chemistry
2009-2010 Associate Professor with Tenure, University of South Carolina, Chemistry
2004-2008 Assistant Professor, University of South Carolina, Chemistry
2003-2004 Visiting Assistant Professor, University of South Carolina, Chemistry
2000-2003 PDF, Johns Hopkins University SOM, Pharmacology

Awards & Professional Activities

2010 South Carolina Governor’s Young Scientist Award for Excellence in Scientific Research 2009 Camille Dreyfus Teacher Scholar Award 2005 New Investigator of the American Heart Association 2000 Canadian Institutes for Health Research Post Doctoral Fellowship 1996 Thomas Neilson Scholarship, McMaster University 1996 National Science and Engineering Research Council Graduate Student Fellowship 1994 National Science and Engineering Research Council Graduate Student Fellowship 1994 Summa Cum Laude, McMaster University

Selected References

Lewallen, D.M., Steckler, C.J., Knuckley, B. Chalmers, M.J. and Thompson, P.R. (2012)  Probing adenylation: Using a fluorescently labelled ATP probe to directly label and immunoprecipitate VopS substrates. Mol. Biosyst. in press.

Lewallen, D.M., Steckler, C.J., Knuckley, B. Chalmers, M.J. and Thompson, P.R. (2012)  Probing adenylation: Using a fluorescently labelled ATP probe to directly label and immunoprecipitate VopS substrates. Mol. Biosyst. in press.

1.     Lewallen, D.M., Steckler, C.J., Knuckley, B. Chalmers, M.J. and Thompson, P.R. (2012)  Probing adenylation: Using a fluorescently labelled ATP probe to directly label and immunoprecipitate VopS substrates. Mol. Biosyst. in press.

Evjenth, R.H., Brenner, A.K., Thompson, P.R., Thomas Arnesen, T., Froystein, N.A., and Lillehaug, J.R. (2012) The human protein N-terminal acetyltransferase hNaa50p (hNat5/hSan) follows an ordered sequential catalytic mechanism: A combined kinetic and NMR study.  J. Biol. Chem. 287, 10081-10088.

Mohamed, B.M., Verma, N.K., Davies, A.M., McGowan, A., Staunton, K.C., Prina-Mello, A., Kelleher, D., Botting, C.H., Causey, C.P., Thompson, P.R., Pruijn, G.J.M., 6, Kisin, E.R., Tkach, A.V., Shvedova, A.A., Volkov, Y. (2012) Citrullination of proteins: a common post-translational modification pathway induced by different nanoparticles in vitro and in vivo. Nanomedicine, in press.

Obianyo, O., and Thompson, P.R. (2012) Kinetic mechanism of protein arginine methyltransferase 6.  J. Biol. Chem. 287, 6062-6071.

Bicker, K.L. Sun, J., Harrell, M., Zhang, Y., Pena, M.M., Thompson, P.R. and Lavigne, J.J. (2012).  Synthetic Lectin Arrays for the Detection and Discrimination of Cancer Associated Glycans and Cell Lines.  Chemical Sciences, 3, 1147-1156.

Dwivedi, N.; Upadhyay, J.; Neeli, I.; Khan, S.; Pattanaik, D., Myers L., Kirou K.A., Hellmich B., Knuckley, B., Thompson, P.R., Crow M.K., Mikuls, T.R., Csernok, E., Radic, M.  (2012) Felty's syndrome autoantibodies bind to deiminated histones and neutrophil extracellular traps. Arthritis Rheum, 64, 982-992.

Jones, J.E., Slack, J.L., Fang, P., Zhang, X., Subramanian, V., Causey, C.P., Coonrod, S.A., Guo, M., Thompson, P.R. (2012) Synthesis and screening of a haloacetamidine containing library to identify PAD4 selective inhibitors.  ACS Chem Biol., 7, 160-165.

Causey, C.P., Jones, J.E., Slack, J.L., Kamei, D., Jones, L.E., Subramanian, V., Knuckley, B., Ebrahimi, P., Chumanevich, A.A., Luo, Y., Hashimoto, H., Sato, M., Hofseth, L.J., and Thompson, P.R. (2011) The development of N-(2-carboxyl)benzoyl-N5-(2-fluoro-1-iminoethyl)-L-ornithine amide (o-F-amidine) and N-α-(2-carboxyl)benzoyl-N5-(2-Chloro-1-iminoethyl)-L-ornithine amide (o-Cl-amidine) as second generation Protein Arginine Deiminase (PAD) inhibitors. J. Med. Chem. 54, 6919-6935.

Taki, H., Gomi, T., Knuckley, B., Thompson, P.R., Vugrek, O., Hirata, K., Miyahara, T., Shinoda, K., Hounoki, H., Sugiyama, E., Usui, I., Urakaze, M., Tobe, K., Ishimoto, T., Inoue, R., Tanaka, A., Mano, H.,  Ogawa, H., Mori, H. (2011) Purification of enzymatically inactive peptidylarginine deiminase type 6 from mouse ovary that reveals hexameric structure different from other dimeric isoforms.  Advances in Bioscience and Biotechnology, 2, 304-310.

Obianyo, O., Causey, C.P., Jones, J.E., Thompson, P.R. (2011) Activity-Based Protein Profiling of Protein Arginine Methyltransferase 1, ACS Chem Biol., 6, 1127-1135.

Rust, H. L., and Thompson, P. R. (2011) Kinase Consensus Sequences: A Breeding Ground for Crosstalk, ACS Chem Biol. 6, 881-892.

Lange, S., Goegel, S., Leung, K-Y., Nicholas, A.P., Causey, C.P., Thompson, P.R., Greene, N.D.E., and, Ferretti, P. (2011) Protein deiminases: New players in the developmentally regulated loss of neural regenerative ability.  Developmental Biology 355, 205-214.

Zhang, X, Gamble, M.J., Stadler, S., Cherrington, B.D., Causey, C.P., Thompson, P.R., Allis, C.D., Kraus, W.L, and Coonrod, S.A. (2011) Genome Wide Analysis Reveals PADI4 to be Predictive of Subsets of Actively Transcribed Genes in Breast Cancer Cells.  PLoS Genetics 7, e1002112.

Slack, J.L., Jones, L.E., Bhatia, M., and Thompson, P.R. (2011) Autodeimination of Protein Arginine Deiminase 4 alters protein-protein interactions but not activity.  Biochemistry 50, 3997-4010.

Rust, H.L., Zurita-Lopez, C.I., Clarke, S., and Thompson, P.R. (2011).  Mechanistic studies on the transcriptional coactivator Protein Arginine Methyltransferase 1.  Biochemistry 50, 3332-3345.

Bicker, K., Sun, J., Lavigne, J.J., and Thompson, P.R. (2011) Boronic acid functionalized peptidyl synthetic lectins: Combinatorial library design, peptide sequencing, and selective glycoprotein recognition.  ACS Combinatorial Science, 13, 232-243.

Chumanev, A.A., Causey, C. P., Knuckley, B. A., Jones, J. E., Poudyal, D., Chumanevich, A. P., Davis, T., Matesic, L. E., Thompson, P. R., and Hofseth, L. J. (2011) Suppression of colitis in mice by Cl-amidine: a novel peptidylarginine deiminase (PAD) inhibitor.  American Journal of Physiology - Gastrointestinal and Liver Physiology, 300, G929-38.

Slack, J., Causey, C.P., Luo, Y, Thompson, P.R. (2011) The Development and Use of Clickable Activity Based Protein Profiling Agents for Protein Arginine Deiminase 4.  ACS Chem Biol. 6, 466-476.

Obianyo, O., Causey, C.P., Osborne, T.C., Jones, J.E., Lee, Y-H, Stallcup, M.R. and Thompson, P.R. (2010) A Chloroacetamidine-based Inactivator of Protein Arginine Methyltransferase 1: Design, Synthesis, and in Vitro and in Vivo Evaluation. Chembiochem in press.

Willis, V, Gizinski, A., Knuckley, B., Causey, C.P., Luo, Y., Banda, N., Holers, V.M., Thompson, P.R.  (2011)  Efficacy of Cl-amidine in the collagen induced model of rheumatoid arthritis.  J. Immuno 186, 4396-4404.

Slack, J.L., Causey, C.P., and Thompson, P.R. (2011) Protein arginine deiminase 4: a target for an epigenetic cancer therapy, Cell Mol Life Sci. 68, 709-720.

Knuckley, B., Causey, C.P., Pellechia, P.J., Cook, P.F., Thompson, P.R. (2010) Haloacetamidine-based Inactivators of Protein Arginine Deiminase 4 (PAD4): Evidence that General Acid Catalysis Promotes Efficient Inactivation. Chembiochem 11, 161 – 165.

Jones, J.E., Causey, C.P., Lovelace, L., Knuckley, B., Flick, H., Lebioda, L., and Thompson, P.R. (2010) Characterization and Inactivation of an Agmatine Deiminase from Helicobacter pylori. Bioorganic Chemistry 38, 62-73.