个人简介

B.A. (Biological Sciences), Occidental College Ph.D. (Cellular & Molecular Biology), University of Missouri-Columbia M.D. Saint Louis University

研究领域

Vaccine design, antibodies, B cells and phage display libraries

My research interest is in understanding the molecular basis for antigen recognition by antibodies using peptide as probes of these interactions. My postdoctoral work involved the initial development of phage-displayed, peptide libraries for this purpose. A peptide library comprises tens of millions of short, variable, amino acid sequences that have been engineered into a viral coat protein, thereby displaying the fusion products on the surface of filamentous bacteriophage. The phage-displayed peptide is linked to an amplifiable readout, encoded on the viral genome. This allows a library to be searched with binding molecules such as antibodies, receptors and enzymes, using affinity-selection to find the rare phage displaying binding peptides. The sequences of binding peptides can be easily determined from clones isolated from affinity-enriched phage pools, by sequencing the region of phage DNA encoding the variable peptides. As a molecular immunologist and physician, I have a strong interest in understanding how the peptide recognition profile of an antibody response may be applied to the development of vaccines and autoimmune diagnostics. One of our most interesting projects involves our search for peptides will bind to human monoclonal antibodies that kill HIV-1. We hope to create a vaccine that will elicit these same antibodies in uninfected people, and thus protect them from AIDS.

近期论文

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Watson, C.T., Steinberg, K.M., Huddleston, J., Warren, R.L., Malig, M., Schein, J., Willsey, A.J., Joy, J.B., Scott, J.K., Graves, T., Wilson, R.K., Holt, R.A., Eichler, E.E., and Breden, F. 2013. Complete Haplotype of the Human Immunoglobulin Heavy Variable IGHV genes from a Single Individual and Characterization of Allelic and Copy Number Variation from Haplotype Sequence Analysis. Am J Hum Genet. 92(4): 530-46. Scott, J.K., Pantophlet, R., Craig, L. 2012. Complex Binding Sites Made to Order. Nature Biotechnol. (News and Views.) 30(2): 154-155. Montero, M., Gulzar, N., Klaric, K.A., Donald, J., Lepik, C., Wu, S., Tsai, S., Julien, J.P., Hessell, A., Wang, S., Lu, S., Burton, D., Pai, E., DeGrado, W., and Scott, J.K. 2012. Neutralizing Epitopes in the MPER of HIV-1 gp41 Are Influenced by the Transmembrane Domain and the Plasma Membrane. J. Virol. 86(6): 2930-2941. Raymond-Bouchard, I., Carroll, C.S., Nesbitt, J.R., Henry, K.A., Pinto, L.J., Moinzadeh, M., Scott, J.K ., Moore, M.M. 2012. The MIRB Ferrisiderophore Transporter of Aspergillus fumigatus: Structural Requirements for Activity. Eukaryot Cell. 11(11): 1333-1344. Singh, H., Henry, K.A., Wu, S.S.T., Chruscinskia, A., Utz, P.J., and Scott, J.K. 2011. Reactivity Profiles of Broadly Neutralizing Anti-HIV-1 Antibodies Are Distinct from Those of Pathogenic Autoantibodies. AIDS. 25(10): 1247-1257. Henry, K.A., Murira, A., van Houten, N.E., Scott, J.K. 2011. Developing Strategies to Enhance and Focus Humoral Immune Responses Using Filamentous Phage as a Model Antigen. Bioeng Bugs. 2(5): 275-283. Romanuik, S.F., Grist, S.M., Gray, B.L., Hohertz, D., Kavanagh, K., Gulzar, N., Scott, J.K., Nirwan, R., Hui, C., Brolo, A.G. and Gordon, R. 2011. Detecting Antibodies Secreted by Trapped Cells Using Extraordinary Optical Transmission. IEEE Sensors. 11(11): 2732-2739. Romanuik, S.F., Grist, S.M., Haq, M., Gray, B.L., Gulzar, N., Scott, J.K., Hohertz, D., Kavanagh, K.L, Nirwan, R., Hui, C, Brolo, A.G. and Gordon, R. 2011. Microfluidic Trapping of Antibody-secreting Cells. J. Med. & Biol. Eng. 31(2): 121-127. Zhu, Z., Qin, H.R., Chen, W., Zhao, Q., Shen, X., Schutte, R., Wang, Y., Ofek, G., Streaker, E., Prabakaranm, P., Fouda, G.G., Liao, H.X., Owens, J., Louder, M., Yang, Y., Klaric, K.A., Moody, M.A., Mascola, J.R., Scott, J.K., Kwong, P.D., Montefiori, D., Haynes, B.F., Tomaras, G.D., Dimitrov, D.S. 2011. Cross-reactive HIV-1-neutralizing Human Monoclonal Antibodies Identified from a Patient with 2F5-like Antibodies. J Virol. 85(21): 11401-11408. Romanuik, S.F., Grist, S.M., Gray, B.L., Hohertz, D., Kavanagh, K., Gulzar, N., Scott, J.K., Nirwan, R., Hui, C., Brolo, A.G., and Gordon, R. 2010. Sensing of Antibodies Secreted by Microfluidically Trapped Cells via Extraordinary Optical Transmission through Nanohole Arrays. IEEE Sensors, 2105-2108. Breden, F., Lepik, C., Longo, N.S., Montero, M., Lipsky, P.E., Scott, J.K. 2010. Comparison of Antibody Repertoires Produced by HIV-1 Infection, Other Chronic and Acute Infections, and Systemic Autoimmune Disease. PLoS ONE 6(3): e16857. Irving, M.B., Craig, L., Menendez, A., van Houten, N.E., Montero, M. and Scott, J.K. 2010. Exploring Peptide Mimics for the Production of Antibodies against Discontinuous Protein Epitopes. Molec. Immunol. 47(5): 1137-1148. van Houten, N.E., Henry, K.A., Smith, G.P. and Scott, J.K. 2010. Engineering Filamentous Phage as a Carrier to Focus Antibody Responses against a Peptide. Vaccine 28(10): 2174-2185. Feldman, A.R., Shapova, Y.A., Wu, S.S.T., Oliver, D.C., Heller, M., McIntosh, L.P., Scott, J.K. and Paetzel, M. 2008. Phage Display and Crystallographic Analysis Reveals Potential Substrate/Binding Site Interactions in the Protein Secretion Chaperone CsaA from Agrobacterium tumefaciens. J. Mol. Biol. 379(3): 457-470. Menendez, A.*, Calarese, D.*, Stanfield, R.L.*, Chow, K.C., Scanlon, C., Kunert, R., Katinger, H., Burton, D.R., Wilson, I.A. ¶ and Scott, J.K. ¶ 2008. A Peptide Inhibitor of HIV-1 Neutralizing Antibody 2G12 Is Not a Structural Mimic of the Natural Carbohydrate Epitope on gp120. FASEB J. 22: 1380-1392. *These authors contributed equally to this work. ¶Co-corresponding authors. Montero, M. *, van Houten, N.E. *, Wang, X. and Scott, J.K. 2008. The Membrane Proximal External Region of the HIV-1 Envelope: A Dominant Site of Antibody Neutralization and Target for Vaccine Design. Microbiol. Mol. Biol. Rev. 72(1): 54-84. *These authors contributed equally to this work.