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Gregory Poon

Assoc. Professor/ Biophysical
Education

B.Sc.Phm., University of Toronto (1998)
Ph.D., University of Toronto, Ph.D. (2003)
PDF, Ontario Cancer Institute (2005-2008)

Specializations

Biophysical chemistry, protein engineering

Biography

Our laboratory is engaged in three lines of research:

1. Transcriptional targeting by the ETS superfamily of transcription factors. ETS-family proteins, which regulate the self-renewal and differentiation of hematopoietic and neural stem cells, exemplify how transcription factors with overlapping DNA sequence preferences achieve target gene specificity. Our interest is to understand the mechanism by which structurally homologous transcription factors discriminate DNA target sites, and to establish chemical control of clinically significant ETS-dependent genes. Our work thus far has revealed a high level of mechanistic heterogeneity in ETS/DNA recognition, including previously unrecognized differences in coupling of preferential hydration and conformation dynamics to site binding. In collaboration with Drs. Dave Boykin and David Wilson, we have also identified lead compounds capable of modulating specific ETS/DNA complexes in vivo and are conducting collaborative preclinical studies to evaluate their therapeutic potential in acute myeloid leukemia, systemic sclerosis, and Epstein-Barr viral oncogenesis in model systems.

 

2.  Toxin engineering. Protein therapeutics capable of conditionally targeting multiple molecular markers are emerging targeted therapeutics. My group has recently engineered structural complementation into the catalytic domain of Pseudomonas exotoxin A, a monomeric ADP-ribosyl transferase that specifically inactivates elongation factor 2 and inhibits ribosomal protein synthesis. Unlike complementing systems based on anthrax toxin, which can be triggered only by extracellular stimuli, the exotoxin-based system is able to respond conditionally to intracellular molecular markers.  We are developing this engineered toxin as a prodrug for targeting complex cellular phenotypes and as a tool for screening sequence-specific protease libraries.

 

3. Biophysical development. In support of our laboratory’s and collaborators’ projects, we develop rigorous, computationally efficient techniques for analyzing complex binding models by calorimetric and other biophysical techniques. One particular area of interest is the explicit formulation of isothermal calorimetric titration (ITC) models in terms of native differential equations, an approach that greatly facilitates the analysis of complex binding systems that would otherwise be recalcitrant to ITC. We have applied our methodology to Ca2+ binding by the EF-hand domain of polycystin-2 and are tackling the binding of cyclic dinucleotides to the virulence factors of V. cholerae.

 

Publications

Citations in PubMed and Google Scholar