Already the only person ever elected to all three of Canada’s science academies, Shoichet is the innovative mind behind breakthroughs ranging from ‘space suits’ for fragile stem cells to polymer-based ‘vehicles’ that could let cancer drugs ‘drive’ to affected areas.
The award—which involves a $140,000 prize—recognizes accomplished women researchers and encourages more young women to enter science and technology careers. (A recent report from Engineers Canada revealed that only 18.3 per cent of undergrad engineering degrees in the country were awarded to women in 2013—an area U of T is changing with record-high female enrolment for 2014.)
“Since I can remember, my Mom encouraged me to have a profession,” says Shoichet. “I did well in math and science in high school and was lucky to be able to dream about what I could contribute. Now I’m following that dream for a living.”
Stem cell ‘space suits’ made of Jell-O
For Shoichet, the key to that dream lies in Jell-O-like materials called hydrogels —networks of polymer chains that swell in water, can thin and flow when forced through a needle, and then set almost immediately. These hydrogels allow stem cells or drugs a better chance of getting to and integrating into the parts of the body where they’re needed.
“If you have a series of wires that are all broken, just throwing in more wires won’t fix things,” says Shoichet. “In the nervous system, for example, we need those wires to be connected to a circuit to work…We need the stem cells to survive long enough to integrate, but we need the cells to integrate in order to survive.”
Shoichet and team have solved this chicken-and-the-egg dilemma with a delivery system that acts as a sort of space-suit, incorporating fragile stem cells in a hydrogel that has survival-promoting ‘life-support’ cells inside the gel. This enables the stem cells to survive long enough to give them a fighting chance to integrate—a stage to which most stem cells implanted into the body fail to reach.
Such transplants could someday lead to truly miraculous treatments for spinal cord injuries, stroke and blindness to name a few— where hydrogel-based ‘vehicles’ could transport specifically-engineered cell groups more safely directly to damaged tissue that needs repairing.
‘Driving’ polymer ‘vehicles’ to treatment sites
Shoichet and team are also designing polymers to deliver specially-engineered nano-scale drugs to specific areas of the brain and spinal cord, stimulating existing stem cells to mend damaged tissue.
To do this without damaging the brain or spinal cord, Shoichet and team take a hydrogel containing the stem-cell-stimulating drug and nano-spheres filled with an additional drug to slow the release of the stem-cell-stimulating drug and inject it directly on top the brain or spinal cord for a local, sustained release to the damaged tissue.
This allows the stem-cell-stimulating drug to be carefully laid onto the brain (or spinal cord), safely getting around the blood barrier (or the blood-spinal-cord barrier), beyond which the drug is able to act to promote repair.
“If I knew how complex the central nervous system was, I wouldn’t have gotten into this field,” Shoichet jokes, laughing. “But it’s this complexity that makes my field so exhilarating and full of promise.”
‘Seep-and-destroy’ cancer treatment
Cancer research caught Shoichet’s interest after a good friend of hers died of breast cancer 10 years ago. Now, Shoichet and team are creating materials that will deliver drugs directly to cancer cells, aiming to overcome some of the horrible side-effects of current cancer treatments.
To do so, they deliver potent drugs to the centre of a cancerous area where they disperse throughout that area and stay around long enough to kill cancer cells, leaving healthy cells largely untouched.
Riding inside the polymers that carry these drugs, nano-beads spread through cancer-stricken areas via the vascular system. At 1/1000 the thickness of a human hair, the beads are small enough to cross the leaky cancerous vasculature but large enough to stop at the more solid healthy vasculature.
Shoichet hopes that these discoveries and many others her team is working on – such as microscopic scaffolding that guides where cells will grow tissues for transplantation – will soon help improve our standard of living.
Culture of collaboration
When those real-world benefits come (some of Shoichet’s work has already been commercialized), she insists that it’s all been possible only through connections with hundreds of colleagues and students.
“Molly is a fantastic collaborator who never gives up on people or ideas,” says Dr. Cindi Morshead, colleague and Anatomy Chair at the U of T’s Donnelly Centre for Cellular + Biomolecular Research. “She just has such an incredible energy.”
The motto of The Shoichet Lab—“Solving Problems Together”—is evident in every aspect of the workplace she’s created: At the end of their time with the facility, students have their lab coats “retired” and hung on a wall of fame like the jerseys of iconic hockey legends.
“PhD and Masters students that come here to learn very quickly end up teaching me about what they’ve been tasked with becoming an expert on,” says Shoichet.
Like the time she and research students discovered that one of their hydrogels not only held its contents properly but the material it was made of itself was therapeutic to the tissues it was delivering drugs to.
“Sometimes discoveries are a slow progression, but that was a bit of an ‘ah-ha!’ moment,” says Shoichet. “When the gel didn’t seem to do anything bad and actually seemed to do something good, we stood back and said, ‘hey, we’ve really got something here.’”
n addition to the honour for Professor Shoichet, U of T and Hospital for Sick Children researcher Dr Vanessa D’Costa received one of this year’s 15 L’Oréal-UNESCO For Women in Science Rising Talent grants for her research into new drug-resistant strains of salmonella.