The making of molecules
For Patrick Gunning, an assistant professor in U of T Mississauga's Department of Chemical and Physical Sciences, working with molecules to develop innovative cancer therapeutics has been a driving force behind his work for the past six years. Now with an Early Research Award (ERA), which secures a significant sum of $150,000 from the Ministry of Research and Innovation, he has funding to further explore this area with the project, Developing Novel Uba1 Molecular Therapeutics: Suppressing the Side-Effects of Aggressive Chemotherapy.
Making molecules that impact the human condition is a huge motivation, says Gunning. In particular, my molecular efforts have focused on targeting the aberrant activation of specific proteins that directly contribute to cancer progression. Gunning's study is primarily concerned with inhibiting the Ubiquitin E1 activating enzyme (Uba1), which has proven to be successful in killing cancer cells, leaving normal cells unharmed, and in helping to delay tumor growth in leukemia studies.
Working in collaboration with Dr. Aaron Schimmer, a researcher with Princess Margaret Hospital, Gunning's ERA-funded project will continue to explore Uba1, further analyzing inhibitors that induce cell death and help to determine the basis for cancer-cell selectivity. The development of Uba1 specific inhibitors would be of incredible importance to Ontario's chemical, biological and drug-discovery industries, as well as patients in the clinic, explains Gunning. Successful validation of these agents as viable stand-alone or adjuvant therapeutics will be of tremendous value to the many Ontarians who suffer greatly from the significant adverse side effects associated with aggressive chemotherapy.
Alleviating the various discomforts from cancer treatment is one aspect of this project, but the researchers are also interested in investigating the fact that current chemotherapy treatment does not work for everyone. Based on today's incidence rates, Gunning estimates that of the 7,000 Ontario residents that were diagnosed with leukemia and lymphomas last year, some 2500 will not respond to traditional chemotherapy. Increasing resistance to conventional methods of chemotherapy necessitates that innovative drug discovery programs remain a high priority in Ontario-specific research, says Gunning. While studies have shown that there have been marked improvements in the areas of detection, treatment and survival, Gunning states that further work on ways to prevent carcinogenesis, which is the process of normal cells transforming into cancer cells, also needs to be explored.
Gunning started working in cancer research while doing his post-doctorate at Yale University in 2004. His supervisor at the time, Professor Andrew D. Hamilton in the Department of Chemistry, significantly influenced Gunning's current research path. Professor Hamilton was instrumental in opening my eyes to the dynamic and exciting field of chemical biology. says Gunning. It is an extremely challenging area of medicinal chemistry, and I think this actually made me more determined to enter this field of research.
