Mechanisms of Disease
Research at TMU:Biomedical Sciences

Research at TMU:
Biomedical Sciences

In 2016, the university introduced a sprawling, new 20,000 ft² ultramodern scientific research facility in North America’s largest urban innovation hub, the MaRS Discovery District. The state-of-the-art space threw the door wide open for leading researchers to create rich collaborations.

Exploration in biomedical science, in particular, has spread in exciting new directions. Over the years, our molecular and cellular scientists have peered into their microscopes to investigate the mysteries of both normal and diseased cells. Their discoveries now form the basis for the biomedical innovations of tomorrow.

Four individual spotlights provide a peek into the biomedical research taking place at the MaRS labs.

Dr. Roberto J. Botelho
Dr. Roberto J. Botelho

TMU professor, Canada Research Chair in Organelle Function and Adaptation

Expertise: Membrane traffic, Lysosomes, Phagocytosis, Macrophages, Lipid Signalling

Back to the fundamentals

To many people, studying cells in a petri dish may seem far removed from daily life — but the impacts are not. Many life-saving disease treatments today were possible only after cell biologists like Dr. Roberto Botelho spent years probing cells’ inner workings.

Dr. Botelho is an expert in cell

organelles

parts of a cell that perform specific functions, much like organs in a human body

— particularly lysosomes (structures that degrade unwanted or dangerous material), and phagosomes (intracellular compartments that sequester engulfed foreign particles such as microbes). His lab investigates how these two work together to digest microbes, and what goes wrong in diseases linked to their function.

“One very pressing problem is how cells adapt to stresses like infection. If we can identify molecules to target for drug therapy, we may be able to engage the molecular circuitry that helps resolve infections.”

For example, the Botelho Lab discovered how macrophages — a type of immune cell — get better at killing bacteria. It happens after they undergo phagocytosis — the process whereby the immune cell engulfs bacteria or microbes. This activates a protein called TFEB, which in turn, powers up lysosomes — those organelles that handle waste.

As a result of the findings, the lab is now investigating the potential for new drugs that resolve infections by activating that TFEB protein.

Dr. Sarah Sabatinos
Dr. Sarah Sabatinos

TMU professor

Expertise: Cell Cycle Checkpoints & DNA Repair, Stress Kinase Singling & Effect(s), Chemotherapy Testing, Anti-Coronavirus Compound Screening

Putting the brakes on disease

Just like cars, cells have “brakes” to stop growth when something is damaged. When these cell cycle checkpoints malfunction, cell growth speeds up and disease such as cancer spreads.

Dr. Sarah Sabatinos researches how this occurs and how to protect cells from copying damaged DNA into harmful mutations. Among other results, the lab recently demonstrated that even moderate rises in temperature alter how cells respond to DNA replication — important insights as the world battles climate change.

“My research in cancer chemotherapeutics is really important to me. I lost my own father to cancer. It’s been incredibly rewarding to target scientific questions that impact our everyday lives.”

As part of an international collaboration, the Sabatinos Lab also helped create a screening program for new boron compounds, which are entirely new molecules for drug development. So far, they’ve identified several new molecules that specifically decrease human coronavirus infection or even stop pancreatic cancer growth.The work originated with the late chemist Dr. Stephen Westcott of Mount Allison University, and Dr. Sabatinos is honoured to continue his legacy.

Dr. Michael Olson
Dr. Michael Olson

TMU professor, Canada Research Chair in Molecular Cell Biology

Expertise: Cytoskeleton, Signal Transduction, Cell Migration, Drug Discovery, Cancer

Dilemmas & conundrums:
Science walks a tightrope

For years, scientists had observed that cells sometimes decide to self-destruct by triggering a series of biochemical steps — called apoptosis — but its purpose remained a mystery.

Dr. Michael Olson recently uncovered its importance: an emergency mechanism that protects the liver after exposure to toxic substances. But in the process of eliminating toxins, liver cells are sacrificed.

“Biomedical science has so many unexplored frontiers. The university’s MaRS Research Facility brings scientists together to collaborate on some of today’s most complex questions.”

Can this liver damage be minimized if scientists step in to halt apoptosis? Yes, but with a major trade-off: increased future risk of liver cancer. Where is the fine line between saving lives now and preventing illness later?

These are the agonizing dilemmas that scientists grapple with. The Olson Lab continues to search for answers by unraveling the function of proteins that cause changes to a cell’s

cytoskeleton

literally a cell’s skeleton, and the internal structure that gives cells their shape

.

Dr. Costin Antonescu
Dr. Costin Antonescu

TMU professor

Expertise: Fundamental and Cancer Cell Biology, Receptor Signaling, Cell Metabolism, Drug Delivery & Discovery

Breaking silos, forging new frontiers

As problems become more complex, scientists from completely different disciplines are joining forces to create new synergies in biomedicine. Dr. Costin Antonescu has been crisscrossing these borders for years.

His lab studies how normal cells and cancer cells interact with and respond to their environment. For over 40 years, scientists knew that the protein clathrin controls how cells take up nutrients from the outside. The Antonescu Lab revealed a surprising new role: directly controlling how cells respond to growth factors that cause cellular proliferation.

“Since coming to TMU, my research has shifted to new and exciting ideas, shaped by rich interactions with colleagues, many of whom practice well outside of my traditional cell biology background.”

Armed with deep knowledge of this uptake process, Dr. Antonescu teamed up with fellow cell biologist Dr. Roberto Botelho and TMU physicist Dr. Raffi Karshafian, an expert in ultrasound and microbubble therapy.

Together, the trio discovered that ultrasound can manipulate cells to take up materials from the outside more quickly. The development could eventually be used to deliver tiny, micro-sized bubbles impregnated with cancer-fighting drugs directly into tumor cells — without damaging healthy surrounding tissue.

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