Roman Melnyk, PhD
My laboratory has a major interest in bacterial protein toxins that cause human diseases. We study these remarkably toxic proteins both because they are high-value targets for therapeutic intervention by small molecules, and to exploit their unique cell-penetrating properties to design intracellular protein delivery vectors. Specifically, we are focused on three distinct aspects related to toxins: (1) on the molecular mechanism by which they cause disease; (2) on discovering and developing novel small-molecule therapeutics that block their action as a novel approach to treat certain toxin-driven infectious diseases; and, (3) on taking advantage of their unique cell-penetrating properties to engineer them into drug- delivery platforms.
- Zhang, Z., Park, M., Tam, J., Auger, A., Beilhartz, G.L., Lacy, D. B., Melnyk, R.A.. Translocation Domain Mutations Affecting Cellular Toxicity Identify the Clostridium difficile Toxin B Pore. Proc. Natl. Acad. Sci. USA (2014); 111(10): 3721-3726
- Tam, J., Beilhartz, G.L., Auger, A., Gupta, P., Therien, A.G., Melnyk R.A.. Small Molecule Inhibitors of Clostridium difficile Toxin B-Induced Cellular Damage. Chemistry & Biology (2015); 22(2): 175-185.
- Auger, A., Park, M, Nitschke, F., Minassian, L.M., Beilhartz, G.L., Minassian, B.A., Melnyk R.A.. Efficient Delivery of Structurally Diverse Protein Cargo into Mammalian Cells by a Bacterial Toxin. Molecular Pharmaceutics (2015); 3(12): 2962-2971
- Chumbler, N.M., Rutherford, S.A., Zhang, Z., Farrow, M.A., Lisher, J.P., Farquhar, E., Giedroc, D.P., Spiller, B.W., Melnyk R.A., Lacy, D.B.. Crystal Structure of Clostridium difficile Toxin A. Nature Microbiology (2016); 1(1): 1-6.
- Orrell KE, Tellgren-Roth, A., DiBernardo, M. Zhang, Z., Cuviello, F., Lundqvist, J., von Heijne, G., Nilsson, I.,, Melnyk RA.. Direct detection of membrane-inserting fragments defines the translocation pores of a family of pathogenic toxins. Journal of Molecular Biology (2018)