Return to Directory

Gregory Poon

Associate Professor
Education

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

Specializations

Biophysical chemistry, protein engineering, phage display, biophysical development

Biography

ETS-family transcription factors, which regulate the self-renewal and differentiation of hematopoietic and neural stem cells, exemplify the long-standing, and as-yet unsolved problem of how structurally conserved transcription factors with overlapping DNA sequence preferences achieve target gene specificity. Our interest is to understand the biophysical mechanism by which these structurally homologous transcription factors discriminate DNA target sites, and to establish chemical control of clinically significant ETS-dependent genes. Our work has revealed a high level of mechanistic heterogeneity in ETS/DNA recognition, including previously unrecognized differences in coupling of hydration and conformation dynamics to site recognition. We are now translating this knowledge to search for compounds that selectively target one or a small subset of ETS/DNA complexes,  with a view of finding targeted transcriptional activators. In addition, we are engaged in major collaborative efforts to design inhibitors of specific ETS/DNA complexes in vivo, and are conducting  collaborative preclinical studies to evaluate their therapeutic potential in acute myeloid leukemia, systemic sclerosis and melanoma in model disease systems.

Publications

Citations in PubMed and Google Scholar

Representative publications:
Esaki, S., Evich, M.G., Erlitzki, N., Germann, M.W., and Poon, G.M.K. Multiple DNA-binding modes for the ETS family transcription factor PU.1. (2017) J Biol Chem. 292, 16044-54.
Xhani, S., Tan, J., Esaki, S., Huang, K., Erlitzki, N., and Poon, G.M.K. (2017) Distinct roles for interfacial hydration in sitespecific DNA recognition by ETS-family transcription factors. J Phys Chem B. 121, 2748-58.
Poon, G.M.K. and Kim, H.M. (2017) Signatures of DNA target selectivity by ETS transcription factors. Transcription. 8, 193-203.
Antony-Debré, I., Leite, J., Paul, A., Mitchell, K., Kim, H.M., Huang, K., Kumar, A., Farahat, A., Bartholdy, B., Narayanagari, S.-R., Carvajal, L., Chen, J., Mantzaris, I., Verma, A., Will, B., Boykin, D.W., Wilson, W.D., Poon, G.M.K., and Steidl, U. (2017) Inhibition of the myeloid master regulator PU.1 as a therapeutic strategy in acute myeloid leukemia. J Clin Invest. doi: 10.1172/JCI92504.

Sign up for our mailing list.