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About Sickkids
About SickKids

Roman Melnyk, PhD

Research Institute
Senior Scientist
Molecular Medicine

University of Toronto
Assistant Professor
Biochemistry


Phone: 416-813-7654 ext. 28557
Email: roman.melnyk@sickkids.ca

Brief Biography

Education & Training:

  • B.Sc. in Biochemistry, McMaster University co-op - 1993-1998
  • PhD in Biochemistry, University of Toronto - 1998-2004
  • Postdoctoral Fellow, Harvard Medical School - 2004-2006

Professional Experience:

  • Senior Scientist in Biology [Drug Discovery] at Merck Frosst Canada, Merck & Co. - 2006-2010

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.  

Publications

Translocation domain mutations affecting cellular toxicity identify the Clostridium difficiel toxin B pore,  Zhang Z, Park M, Tam J, Auger A, Beilhartz GL, Lacy DB, Melnyk RA. Proc Natl Acad Sci USA 2014 111(10)l 3721-6;

Impact of primer-induced conformational dynamics of HIV-1 reverse transcriptase on polymerase translocation and inhibition. Auger A, Beilhartz GL, Zhu S, Cauchon E, Falgueyret JP, Grobler JA, Ehteshami M, Gotte M, Melnyk RA.
J Biol Chem. 2011 Aug; 286(34) 29575-83

A high-throughput continuous assay for screening and characterization of inhibitors of HIV reverse-transcriptase DNA polymerase activity. Cauchon E, Falgueyret JP, Auger A, Melnyk RA. J Biomol Screen. 2011 Jun;16(5):518-24.

An activity-based probe for high-throughput measurements of triacylglycerol lipases. Tam J, Henault M, Li L, Wang Z, Partridge AW, Melnyk RA. Anal Biochem. 2011 Jul 15;414(2):254-60

A loop network within the anthrax toxin pore positions the phenylalanine clamp in an active conformation. Melnyk RA, Collier RJ.
Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9802-7

A phenylalanine clamp catalyzes protein translocation through the anthrax toxin pore. *Krantz BA, *Melnyk RA, Zhang S, Juris SJ, Lacy DB, Wu Z, Finkelstein A, Collier RJ. Science. 2005 Jul 29;309(5735):777-81 *co-first authors

Structural determinants for the binding of anthrax lethal factor to oligomeric protective antigen. Melnyk RA, Hewitt KM, Lacy DB, Lin HC, Gessner CR, Li S, Woods VL Jr, Collier RJ. J Biol Chem. 2006 Jan 20;281(3):1630-5.

Visit PubMed for a full list of Melnyk's publications. 

Intellectual Property

Translocation-defective recombinant holotoxins of clostridium difficile as immuogens