Roman A. Melnyk

Roman A. Melnyk

Assistant Professor

BSc, Biochemistry, McMaster University co-op, 1993-1998
PhD, Biochemistry, University of Toronto, 1998-2004
Postdoc, Harvard Medical School, 2004-2006
Senior Scientist in Biology (Drug Discovery), Merck Frosst Canada, Merck & Co., 2006-2010

Lab Melnyk Lab
Office Phone 416-813-7654 ext. 328557
Email roman.melnyk@sickkids.ca

Research Lab

lab

Research Description

Bacterial Toxin Pathogenesis: Molecular Mechanisms & Drug Discovery

Research Interests

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

Research Activities

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.

Awards & Distinctions

2014 — Early Researcher Award, Ontario Ministry of Economic Development & Innovation

Courses Taught

BCH 2024H Frontiers in Drug Discovery
BCH210H Fall Biochemistry I: Proteins, Lipids and Metabolism
BCH473Y Advanced Research Project in Biochemistry

Publications

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