RI-MUHC ANNUAL REPORT 2020

Physicians, over the course of medical history, have considered a range of individual factors in determining how to treat afflictions. But new discoveries, technologies and approaches have revolutionized personalized medicine, and scientists at the Research Institute of the McGill University Health Centre (RI-MUHC) are at the vanguard of this revolution. Their investigations are leading to greater understanding of our unique bodies, and how best to keep us healthy.

Through this small sampling of their work, discover why our researchers are committed to driving personalized medicine.

• Ensuring mobility: the “Hip-Mobile”
• Introducing your microbial self
• Tapping the inexhaustible capacity of liquid biopsies
• Investigating genetic profiles for cancer patients

ENSURING MOBILITY: THE “HIP-MOBILE”

Hip fractures in elderly patients result in a loss of mobility that diminishes their overall health and well-being. Dr. Suzanne Morin, of the Metabolic Disorders and Complications Program, is committed to finding ways to ensure patients recover from their fractures and don’t suffer a second one. She and her team have developed and are testing a new rehabilitation technology: the “Hip-Mobile,” a “smart” insole that patients insert in their shoe. Patients agreeing to participate in an extended rehabilitation project are given initial training and then monitored over an eight-month period by the smart insole, which communicates with a tablet via Bluetooth. These results are linked to Dr. Morin’s lab, allowing her to track the frequency and quality of the patient’s rehabilitation and to adjust the program as necessary.

“This approach provides the patient with a personalized rehabilitation program remotely. They benefit from staying in their own home and receiving simple coaching through the program on their tablet,” says Dr. Morin. “There are inevitable challenges in using new technology with the very elderly, but people as old as 98 have successfully completed the program.”

Small differences can make a big change

Dr. Morin’s extended study is providing additional insights. “As participants become more mobile, their perceptions of their health and their abilities change significantly. So, in addition to providing rehab, we are acquiring information about their general strength and mobility, and even their mood,” she says. “We want this approach to translate into better clinical outcomes because as we age, even small differences can make a big change in our ability to do the things we enjoy.”

INTRODUCING YOUR MICROBIAL SELF

Your microbiome, the accumulation of microbes living in and on the body, creates your unique “microbial self.” The better you know this self, the better you can understand certain health issues.

“This microbiome can be beneficial or detrimental to human health, depending on its composition,” says Irah King (PhD) of the Transitional Research in Respiratory Diseases Program. “It can predispose you to a condition that may be dictated by a genetic difference, or you can have a genetic predisposition which might alter the microbiome and therefore lead to a different state of health.”

Irah King’s research addresses how the microbiome affects the immune system and how that may relate to such autoimmune diseases as psoriasis, inflammatory bowel disease, or even respiratory disease. “The gut holds the most microbial species and the most immune cells, creating an intimate relationship between the two. The microbiome may influence the immune system, which may then influence disease,” he says. “We want to understand how a given treatment will interact with both your genetic and your ‘microbial’ self.”

Why a gnotobiotic research platform?

Irah King is the director of the RI-MUHC’s new Gnotobiotic Research Platform, a resource for the study of animal models, primarily mice, that have an identical genetic make-up and are either microbe-free or have a known, controlled microbial composition. The facility, to be opened in the coming year, will enable researchers to control and assess the relationship between genetics and microbiomes. “We will be able to manipulate the microbiota while everything else remains the same,” says King. “Then we can focus on causation rather than simply on identifying correlation.”

TAPPING THE INEXHAUSTIBLE CAPACITY OF LIQUID BIOPSIES

Tumour biopsies for diagnosing cancer and monitoring treatment usually involve removing a tissue sample, but that process collects material from a small portion of the tumour with no guarantee that it bears the most important information. Conversely, liquid biopsies through blood tests allow the physician to collect material from the entire tumour in a timely and considerably less intrusive manner than in traditional biopsy.

Cells release extracellular vesicles into the blood at a regular rate. These vesicles—in particular, exosomes—mediate intercellular communication and carry cargo such as proteins or nucleic acids. Cancer cells also release unique exosomes, each one being representative of the cell from which it came.

“Exosomes enter into the blood from every cell in the tumour, so with sufficiently sensitive detection methods, we can track mutations within the cancer, giving these exosomes diagnostic potential,” says Dr. Janusz Rak, senior scientist in the Child Health and Human Development Program. “We’re reaching the point in the molecular characterization of cancers where these features could be used for making clinical decisions.”

Research is exploring how to understand the information deposited into the bloodstream by the cancer. “We’re identifying ‘signatures’ in this genetic information so we can determine what a tumour is doing,” says Dr. Peter Metrakos, leader of the Cancer Research Program. “If mutations go down, we would know our treatment is working.”

A vision for applied nanomedicine

Drs. Rak and Metrakos are co-leads on a Canada Foundation for Innovation application to establish a Centre for Applied Nanomedicine at the RI-MUHC. “This facility would support our research into these vesicles in diagnostic and other contexts,” says Dr. Rak. “Liquid biopsies have an inexhaustible capacity to reflect this everchanging malignant disease that affects people.”

INVESTIGATING GENETIC PROFILES FOR CANCER PATIENTS

It has long been known that genetic make-up affects one’s risk of cancer. For instance, while less than one percent of women will develop ovarian cancer, those carrying a particular mutation have a risk of forty to sixty percent. It is important for both the individual and physician to know each patient’s genetic makeup and select the best therapy.

Enter Oncodrive, a project led by Patricia Tonin (PhD), associate leader of the Cancer Research Program, who has been involved in the discovery of several genetic mutations that predict the likelihood of developing the disease. “Oncodrive aims to improve the management of cancer patients by deriving the individual’s entire genetic sequence,” she explains. “Many genetic mutations measurably affect risk, and that information should be provided to people with those mutations and to their physicians. As well, certain genetic mutations can affect a patient’s response to specific therapies, which then influences the choice of treatment.”

Through Oncodrive databases, physicians will have access to the patient’s genetic profile and be able to adapt treatment appropriately, applying more aggressive therapies for patients whose genes suggest they will be subject to aggressive cancers. Researchers will also draw on the database to identify other mutations that could contribute to a patient’s chances of developing cancer.

Starting with MUHC breast cancer patients

Oncodrive will initially focus on collecting genetic information from breast cancer patients at the MUHC. “Women with breast cancer tend to be aware of the role of genetic mutations and the uses of genetic testing, and are probably more ready to look at the rest of the genome to see what other factors could be contributing to their risk or affecting their treatment,” says Patricia Tonin.