Leadership comes in many shapes and forms – but not all are successful. Dr. Michael Weinfeld, University of Alberta professor in the department of oncology, insists that there is no “I” in “team.” In fact, he’d prefer that he be known as part of a “Research Rock Group,” rather than as a “Research Rockstar” himself, as his current work involves the efforts of at least 15 principal investigators within Alberta. He just happens to be leading and coordinating it.
“Michael is the best person for the job,” says Dr. Jack Tuszynski, Allard Chair and University of Alberta professor in the department of oncology. “Everybody likes Mike.”
Tuszynski is one of the investigators involved in a new study for which the Alberta Cancer Foundation has recently awarded $2.9 million over the next three years. The funding supports the unusually large and diverse team of scientists in its goal of creating new compounds (chemicals that have not been formed into drug-like structures yet) that will make cancer cells more sensitive to current treatments: radiation, chemotherapy and drugs.
“This is a very uncommon situation, where you bring together a spectrum of researchers and clinicians to solve the problem. In the past it’s been more of a sporadic, one group or two collaborating – 15 people is a big team,” Tuszynski says. “Mike understands all aspects of the project like nobody else.”
Weinfeld stresses that the key to this study is its multi-disciplinary design, including input and research from DNA repair specialists, computer specialists, chemists, imaging specialists and pharmacologists. The investigators are located across Alberta, employed by the University of Lethbridge, University of Calgary and University of Alberta with a bit of help from the Centre for Drug Research and Development in Vancouver.
In 1982, Weinfeld came to Canada from England to study at the Chalk River Laboratories in Ontario. With his chemistry background, he worked with radiation biologists at the nuclear lab before moving west to Edmonton in 1985 to work at the Cross Cancer Institute as a post-doctoral fellow. “And I stayed,” he says, referring both to Canada and the Cross. “In 1989, one of the chemists here at the Cross left to go to the States and I inherited that lab.”
His lab, and 30 years worth of studies in it, focuses on DNA repair – providing a plethora of experience and base knowledge for study and research that began over the late summer and early fall of 2015. “Radiation and many chemotherapeutic drugs kill cells by damaging their DNA,” Weinfeld says. “Often, we find that cancers are resistant to therapy, and part of the reason for that is their capacity to repair the damage.” This concept is intriguing to cancer researchers, and Weinfeld’s team wants to do something about it.
DNA damage is a regular occurrence for all living beings and a detection and repair system, made up of proteins called enzymes, mends this damage. But problems arise if cancer cells repair themselves too well after chemotherapy or radiation treatment – some of these cancer cells will survive, causing patients to relapse. Weinfeld’s team is building on research his lab, and Tuszynski’s, has already completed about two enzymes – PNKP and ERCC1-XPF – that operate in key DNA repair pathways.
The team has set a multi-step approach within its study – first, it will develop chemical compounds that inhibit the PNKP and ERCC1-XPF enzymes to stop their ability to repair cancer cells. After, the goal is to make these compounds work well in cells initially grown in the lab. Subsequently, the team will formulate these compounds to one day be administrable to cancer patients as drugs and ensure the compounds target only cancer cells and not normal cells by packaging them in a specific way.
“Let’s say that you’re going in for radiation,” Weinfeld says. “Before your radiation, you’ll be injected with one of the compounds that we think will work, and it should make the cells more sensitive to the radiation.”
Ideally, the invented drug will inhibit key enzymes, making cancer cells more sensitive to radiation or chemotherapy by reducing the chance of cancer cells repairing themselves. Eliminating the chance of repair means all cancer cells should die, which in turn should also eliminate the chance of relapse.
“The target is, initially anyway, in colorectal cancer,” Weinfeld says. “Although, we think this research will apply to many cancers.”
It makes sense to start with colorectal cancer because it’s one of the “big four” – lung, breast, prostate and colon – cancers that have the highest incidence rate. Also, breast cancer is found mainly in women, and prostate only in men, yet colon cancer occurs quite evenly between the sexes and provides a good variety of future clinical trial candidates.
Dr. Afsaneh Lavasanifar, University of Alberta professor in the Faculty of Pharmacy and Pharmaceutical Sciences, is one of the principal investigators on Weinfeld’s team. She has the difficult task of transforming the solid compounds the group’s chemists make into injectable solutions the body will accept.
Some compounds cannot be injected because they can’t be made soluble, Lavasanifar explains. And many of these drug candidates (or compounds) may cause toxicity within the patient. “One way to avoid this problem is to package [the compounds] into particles in the nanometre size range,” she says, adding that when you inject them into patients at that size, the drug won’t have to be metabolized before it reaches the cancer cells.
“These nanoparticles can dictate where the drug goes: not to the normal cells and tissues,” Lavasanifar says. “They can be designed to bring the drug only to cancer cells.”
It typically takes about a decade to develop a new drug that can enter into clinical trials and be used on cancer patients.
Even though Weinfeld and Tuszynski’s labs have already developed the first compounds that inhibit enzymes PNKP and ERCC1-XPF in research – they’re not drugs yet. “We’re a long way from a drug,” Weinfeld says.
For now, the Alberta Cancer Foundation’s investment will carry them for three years. In three to five years, Weinfeld says his team’s goal is to have two good compounds that will target these enzymes and that will be what they report to the Alberta Cancer Foundation on.
“I’m really happy to be a part of this team, and I have to give [Michael] credit for bringing all of these different people together. It wasn’t an easy process and was a competitive program,” Lavasanifar says. “This is a unique situation and can lead to bigger things with this team and different areas of research.”
“It’s worth noting that DNA repair got the Nobel Prize for Chemistry this year,” Weinfeld adds. “It’s a big area of research.” One he’s obviously very passionate about, having studied it for so long already, with no signs of slowing down or changing course.
Everybody Likes Mike
Do you have a family?
I have a wife and three grown children: two daughters and a son.
Are any of them into science and research?
No, they were smart enough to stay away from it. My son is in university though, so maybe, but he’s more into the arts.
What are your hobbies?
I used to play soccer a lot. I do like scuba diving if I can do it and there’s time.
What was the best work-related place you’ve travelled to?
Back in the late-’90s, I went on a sabbatical to Clare Hall Laboratory in Hertfordshire, U.K., which is a cancer research lab with one of the guys who won the Nobel Prize in Chemistry this year. (The 2015 Nobel Prize in Chemistry was jointly awarded to Tomas Lindahl, Paul Modrich and Aziz Sancar for DNA repair studies.)
What was the best non-work-related place you’ve travelled to?
When the kids were younger, we’d go camping, especially on the May long weekend. My colleagues would ask, ‘Where are you going?’ and then they’d go in the opposite direction because they knew that we would always get the snow. It worked for them. The national parks and provincial parks in Canada are a real treasure – more Canadians should value them because they’re just exceptional.
If you weren’t a researcher you would be…
Something that I like is politics. My wife was the campaign manager for Linda Duncan, the NDP Member of Parliament who retained her seat in Alberta. One thing I would like to see is more scientists and engineers in our parliament and legislatures. There are so few. That’s something I bore my friends with all the time: provincial politics.