The Department

In The News:
 

Unique mechanism for vinca site tubulin binding drug DZ-2384 without neurotoxicity – a major advancement for microtubule targeting agents.

In 2013, Diazon Pharmaceuticals teamed up with The Laboratory for Therapeutic Development (LTD) to identify the mechanism of action of a potential new anticancer agent called DZ-2384.  Members of the LTD, Dr. Joseph Tcherkezian, Cynthia Bernier, Dr. Yannève Rolland and Claude Godbout carried out functional genomic screens to identify the anti-mitotic mechanism.  They then went on to characterize its unique effects on microtubule dynamics compared with other anti-mitotics as well as to determine the activity of the compound in several mouse tumor models.  The study, published in Science Translational Medicine, was led by Drs. Anne Roulston and Gordon Shore along with Dr. Gary Brouhard Dept of Biology, and includes as collaborators GCRC members Drs. Peter Siegel and George Zogopoulos as well as several international labs.

Microtubule targeting agents (MTAs) form the basis of many chemotherapeutic regimens currently used in the treatment of solid tumors and leukemias.  These agents, which include taxanes (paclitaxel, docetaxel) and vinca alkaloids (vinblastine and vinorelbine), are accompanied by toxic side effects including peripheral neuropathy, which often results in a reduction or delay in dosing and can leave lasting effects on patients after therapy has been completed.

This study uncovers the unique mechanism by which DZ-2384 is very effective at targeting cancer cells by inhibiting mitosis, yet preserves the microtubule network in non-dividing cells including primary neurons resulting in a superior safety margin in rodent models. By analyzing the  high resolution structure of tubulin with different compounds, the study demonstrates that DZ-2384 binds at the vinca site but induces a distinctive change in the curvature of tubulin protofilaments compared to vincas, which may explain its unusual effects on microtubule dynamics and decreased toxicity.

The way that DZ-2384 and vincas interact with tubulin sheds light on the role that tubulin protofilament curvature plays in microtubule dynamics and provides structural insight into the design of improved microtubule targeting agents that are safer for patients. [2016 November 17].

Link to Article in Science Translational Medicine
See Press Release Here
Link to Diazon Pharmaceuticals
Link to LTD


McGill University Medal for Exceptional Academic Achievement for 2016

The presentation of the McGill University Medal for Exceptional Academic Achievement was given to Dr. Philip Branton at today's Spring Convocation. This award acknowledges retired members of McGill University's academic staff who are uniquely deserving in light of their exceptional contributions to their discipline, to the University and to society at large.  Phil is an internationally renowned scientist that has dedicated much of the last two decades of his career to the betterment of cancer research in Canada, all while promoting its accomplishment at the international stage.  Not only has he been a leader at McGill, he has undeniably put his stamp on the course of cancer research at the national level. Congratulations to Phil who is most deserving! [2016 June 6].

 


Vanier Scholarship Winner 

Congratulations to Shawn McGuirk, from Dr. Julie St-Pierre’s lab, on being one of the top 11 Ph.D. McGill recipients of the 2015 Vanier Scholarships at McGill. This scholarship is administered by Canada’s three federal granting agencies: CIHR, NSERC and SSHRC. This prestigious award aims to attract and retain world-class doctoral students by supporting students who demonstrate a high standard of scholarly achievement in graduate studies and leadership skills. This award is a major accomplishment and Shawn McGuirk is to be congratulated for his excellent work on Impact of PGC-1 on the development of therapeutic resistance in breast cancer (Granting Agency: CIHR). See Vanier Scholars 2015  [2015 Dec. 11]