It’s 8 a.m. Dr. Kirk McManus and Dr. Mark Nachtigal have each already logged three to four hours at the lab.

Their collaborative research project was recently awarded two years’ joint funding from Ovarian Cancer Canada and the Cancer Research Society.

“This funding enables groundbreaking research on what may be another biomarker for ovarian cancer,” says Dr. McManus; Associate Professor, Department of Biochemistry and Medical Genetics, University of Manitoba; Senior Scientist, Research Institute in Oncology and Hematology, CancerCare Manitoba. “If we confirm our hypothesis, there will be a new target for treatment and this grant could be extremely impactful in helping to address a major challenge in ovarian cancer – drug resistance.”

Despite the early hour, both are excited to talk science. Their current project focusses on an event at the molecular level that may trigger the onset of ovarian cancer. If proven, it would provide a basis for testing new drug targets and in turn inform development of more effective treatments.

Specifically, these Senior Scientists are investigating a protein called RBX1, which normally tags proteins that will be broken down. Their study examines whether RBX1 mutations lead to “chromosome instability,” or ongoing changes in DNA that create a genetic shake-up commonly thought to contribute to both cancer and related drug resistance.

“Chromosome instability is like a nefarious blackjack dealer, shuffling in and tossing out different cards to mess up the deck,” explains Dr. McManus. “In this case, they’re shuffling genetic material and affecting ongoing changes to DNA content. Our research looks at whether a defect in RBX1 leads to this instability.”

Preliminary studies into the prevalence of RBX1 defects showed that 80 per cent of high grade serous ovarian cancer samples were missing one copy of the RBX1 gene, where usually there are two copies. Drs. McManus and Nachtigal now seek to exploit this defect to better target and kill cancer cells.

“Targeting the cause of chromosome instability would help reduce the complexity of a tumour,” says Dr. Nachtigal; Associate Professor, Department of Biochemistry and Medical Genetics, University of Manitoba; Senior Scientist, Research Institute in Oncology and Hematology, CancerCare Manitoba. “If we can find a way to do this, it would advance efforts to get ahead of drug resistance and also improve treatment for recurrence.”

“We have been learning about the biology of ovarian cancer for more than 20 years, using samples donated by patients,” says Dr. Nachtigal, a driving force behind the biobanking program at CancerCare Manitoba and a strong advocate for tissue donation.

“Donated tissue samples are extremely valuable to fundamental research studies like ours. This project depends on the participation and cooperation of patients,” says Dr. Nachtigal.

Research hits close to home

Women and families in Winnipeg, Manitoba may recognize Dr. Nachtigal and Dr. McManus from events in and around town. In addition to their research, they take an active part in the local community dedicated to making a difference.

“Eleven years ago, I lost my mother to ovarian cancer. Since then, we’ve been huge supporters of Ovarian Cancer Canada,” says Dr. McManus. “We’ve participated in the Walk of Hope for a decade now because we’ve personally felt the impact of this disease. That’s why we are testing different directions to learn more about its origins and develop better treatment options.”

“We’re passionate about our work and doing everything we can to see improved outcomes for women who have been diagnosed,” says Dr. Nachtigal, whose own family is also deeply affected. “A lot of researchers across Canada are committed to overcoming ovarian cancer. I want you to know that we’re in this for you.”