With approximately $1.1 billion awarded in research funds, U of T has been recognized as a major force in research-intensive education across the globe. But you, like me, may wonder—what kind of research is this? Who does it? How can I access it?
These were some of the questions being discussed at UTM’s Experiential Education Office last year, when they decided to launch the Lecture Me! series for 2016.
“As part of the community outreach efforts created by my office and those that we support, I identified a need and desire to bring UTM outside the walls of our campus and right into the community,” says Melissa Berger, the community outreach coordinator at the Experiential Education Office at UTM. “What better way to showcase the work that our outstanding researchers are doing than to create an event in which we as a campus can provide our community with access to the brilliant minds that make up the faculty roster at UTM?”
The program, which will essentially be a series of lectures by UTM faculty, is hosted at the Mississauga Central Library. The lectures are open to all, which can include fellow faculty, students (current and prospective), alumni, and the general community within Mississauga and Region of Peel.
The series will feature multidisciplinary research by a different faculty member each month, who will host a free lecture describing the research they are conducting.
“This will also give [the] community a basis [through] which they can interact with our researchers and gain insights into the work that UTM is conducting in a more intimate setting,” says Berger.
Last Tuesday, Patrick Gunning of the chemical and physical sciences department was the first to present in the series, with his talk titled: “A Beginner’s Guide to Killing Cancer Cells”.
Professor Ulrich Krull, the interim vice-president at UTM, gave opening remarks at the event.
“These presentations are designed to showcase the nature and the types of forefront research happening at UTM,” says Krull.
Krull highlighted some historic contributions made by UTM faculty in a wide variety of fields, ranging from presenting original data in describing what plate tectonics were, to playing a significant role in the success of the geological expeditions of the Apollo mission.
He emphasizes, however, that, “the understanding of science is rooted in its commitment to the betterment of humanity”. He also highlights the progress being made at UTM in the areas of health care research and drug discovery.
Gunning started his talk with a discussion on the approach taken by his group to accelerate drug discovery.
He says, “This is done by combining design, computational techniques, and synthesis.”
“We, as chemists, look at the human body as a large reaction chamber,” says Gunning, when describing his approach towards understanding the mediation of biological processes by small molecules. “This is why we target specific molecules, and one such molecule, also known as the master regulator of many human cancers, is STAT3.”
Signal Transducer and Activator of Transcription 3, or STAT3, as Gunning elaborates, has also been called an oncogene (a gene that can transform cells into tumour cells). He mentions how in normal cells, STAT3 is transiently active, while in cancer cells it is hyper-activated. In general, Gunning describes how cancer cells are essentially immortal, since they evade all natural processes leading to cell death.
The first step towards drug discovery, as Gunning says, is to aim for high potency and selectivity.
“With a dosage of one microgram [….] drug molecules will reach every organ in the body within four minutes,” he says. Gunning adds, “With a one in a million chance of your drug interacting with the target molecule, we need it to be selective when it sticks, and we need it to stick well.”
The next question, he says, that his group needs to ask is: does it bind to other molecules?
“We don’t want our molecule to touch healthy cells,” says Gunning, emphasizing how selectivity will allow low toxicity, not common for current cancer treatments.
After experimenting with multiple synthesis combinations to reach the drug design allowing for maximum potency, Gunning says the drug molecule will advance into pre-clinical validation with mouse models pre-engrafted with cancerous tumours.
“The liver is the Achilles heel for most medicinal chemists,” says Gunning, when stressing the importance of a balanced bioavailability of the drug in a system. “We need to test the molecule in a living system and see what the liver does—does it trash the drug?”
He mentions how the first compound that they designed, BP-1-102, actually disappeared from the system within 10 minutes. He continues to say, “The solution, as it is for many things, was organic chemistry.”
Gunning describes how his team returned to the drawing board and repeated each step mentioned above with modifications, which finally allowed them to produce a molecule that was successful through the pre-clinical validation.
Treatment with Compound X—the identity of which Gunning holds back for now—results in the same percentage tumour shrinkage as the current Standard of Care.
“We see the same result with one drug that is non-toxic, as with three drugs that are super toxic, one of them being nitrogen mustard,” he says.
Gunning mentions how this work has recently been funded by Venture Capital. Compound X is now in advanced pre-clinical trials, and will be going into Phase 1 clinical trials for one of the most common and malignant glial tumours, Glioblastoma Multiforme.
“35% of patients are under palliative care, with a chance of [this] disease recurring,“ he says. “This tumour that is unresponsive to radiation and drugs—but our drug shuts down division and shows tumour shrinkage.”
The drug has shown similar results in metastasizing breast cancer, multiple myeloma, and acute myeloid leukemia.
“It takes years for a drug to reach clinical trials, […] and even then, we cannot predict how it will behave in the human body,” says Gunning. For now, based on the results, repeated testing, and rigorous investigation, he remains hopeful for the drug’s success.
