研究领域

Bacterial protein toxins can play an important role in the establishment and propagation of numerous infectious diseases. The most potent toxins, including diphtheria, tetanus and anthrax toxins are multi-functional proteins that possess the remarkable ability to direct their own entry into cells through the formation of protein-conducting pores in the host membrane, through which the highly toxic enzymatic subunits traverse through. Since bacterial toxins are often solely responsible for the symptoms of many diseases, blocking their action on mammalian cells represents an attractive approach to potentially treat the symptoms of these devastating bacterial diseases. Using chemical biology and targeted drug discovery approaches combined with molecular biophysics and structural analysis we seek to identify and validate host & toxin targets and discover small molecule hits for further exploration and development. In addition, owing to the unique ability of these toxins to specifically and efficiently deliver their toxic enzymes into cells, an often insurmountable task for many protein-based drugs, we aim to develop toxin-delivery platforms to shuttle otherwise non-cell penetrant therapeutics into cells.

Drug discovery Bacterial pathogenesis Structure & function of bacterial toxins Biophysics of membrane protein transport Membrane proteins

近期论文

查看导师新发文章 （温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

Efficient Delivery of Structurally Diverse Protein Cargo into Mammalian Cells by a Bacterial Toxin Auger, A., Park., M., Nitschke, F., Minassian, L.M., Beilhartz, G.L., Minassian, B.A., Melnyk, R.A. MOL PHARM, 2015; 12(8): 120-28 Small Molecule Inhibitors of Clostridium difficile Toxin B-Induced Cellular Damage Tam, J., Beilhartz, G.L., Auger, A., Gupta, P., Therien, A.G., Melnyk, R.A. CHEM BIOL, 2015; 19(22): 175-85 Derivatives of Mesoxalic Acid Block Translocation of HIV-1 Reverse Transcriptase Bernatchez, J.A., Paul, R., Tchesnokov, E.P., Ngure, M., Beilhartz, G.L., Berghuis, A.M., Lavoie, R., Li, L., Auger, A., Melnyk. R.A., Grobler, J.A., Miller, M.D., Hazuda, D.J., Hecht, S.M., Götte, M. J BIOL CHEM, 2015; 290(3): 1474-84 Translocation Domain Mutations Affecting Cellular Toxicity Identify the Clostridium difficile Toxin B Pore Zhang, Z., Park, M., Tam, J., Auger, A., Beilhartz, G.L., Lacy, D. B., Melnyk, R.A., PROC NATL ACAD SCI, 2014; 111(10): 3721-6 Impact of Primer-Induced Conformational Dynamics of HIV-1 Reverse Transcriptase on Polymerase Translocation and Inhibition Auger, A., Beilhartz, G.L., Zhu, S., Chauchon, E., Falgueyret, J.-P., Grobler, J.A., Götte, M. and Melnyk, R.A. J BIOL CHEM, 2011; 286(34): 29575-29583 A Loop Network within the Anthrax Toxin Pore Positions the Phenylalanine Clamp in an Active Conformation Melnyk, R.A., and Collier, R.J., PROC NATL ACAD SCI 2006;103(26): 9802-9807 Structural Determinants for the Binding of Anthrax Lethal Factor to Oligomeric Protective Antigen Melnyk, R.A., Hewitt, K.M, Lacy, D.B., Lin, H.C., Gessner, C., Woods, V.L., Collier, R.J., J BIOL CHEM. 2006; 281(3): 1630-1635 A Model of Anthrax Toxin Lethal Factor Bound to Protective Antigen Lacy DB, Lin HC, Melnyk, R.A., Shueler-Furman O, Reither L, Cunningham K, Baker D, Collier RJ PROC NATL ACAD SCI 2005;102(45): 16409-14 A Phenylalanine Clamp Catalyzes Translocation Through the Anthrax Toxin Pore ‡Krantz, B.A., ‡Melnyk, R.A., Zhang, S., Juris, S.J., Lacy D.B., Wu Z., Finkelstein, A., Collier, R.J., ‡ co-first author SCIENCE 2005; 309(5735):777-781