10th Anniversary Researcher Spotlight: Ayesha Saleem

Throughout 2024-2025, Research Manitoba celebrates our 10th anniversary year. As we mark this achievement, we will be looking back at some of our past funded researchers to highlight their success.

Message received: A local researcher says the body’s communication system could hold the key to boosting health and preventing disease.

   Profile written by: Brian Cole

Cells are the building blocks of life.

These tiny organisms are essentially responsible for the form and function of every living thing on earth, including humans. Simply put, they are responsible for keeping us alive and healthy.

 So, it should surprise no one to learn that these complex living things – scientists estimate the human body has about 32 trillion of them – are supported by many components that carry out a number of specific functions vital to maintaining life. In order to do that, cells must communicate with each other to achieve various goals. But how they communicate – and how that communications system could be harnessed to enhance human health or prevent disease – is a matter of intense study around the world.

 In Winnipeg, for example, researcher Ayesha Saleem is investigating how cell communication is facilitated by microscopic particles known as extracellular vesicles, or EVs for short. Specifically, her research is designed to better understand how EVs influence health and well-being, with a particular focus on exercise, the progression or prevention of metabolic disease, and development of the fetus.

An associate professor in the Faculty of Kinesiology and Recreation Management at the University of Manitoba and a principal investigator at the Children’s Hospital Research Institute of Manitoba (CHRIM), Saleem says cells use EVs to communicate much the way people use emails.

As she explains, emails sent from one person to another can include text, photographs, videos and sound files. EVs operate much the same way, except their messages contain different biological material – DNA, mRNA, proteins, lipids – messages that can determine how tall we are, the color of our eyes, or support our immune system in fighting diseases such as cancer or diabetes.

“When they (EVs) are released from the parent cells and get taken up by the recipient cells, the message gets transported. So, once the recipient cell picks them up, they (the messages inside the EV) can change its (the recipient cell’s) function,” she says. “And it’s not just one cell. It can perpetuate communication on a whole- body level.

”The key, is figuring out what messages the EVs are carrying. hat can change, depending on the environmental conditions of the cell,” she says. “If the cells are happy, and everything is okay, the cells are going to send different types of signals than if the cells were in some sort of situation where (they are experiencing) some kind of stress”.

Interestingly, scientists did not really know much about how EVs functioned until very recently. First observed in the 1940s, EVs were initially thought to be irrelevant. “They were dismissed as cellular dust, just (cellular waste) being released from cells,” says Saleem. But by the early 2000s, scientists started to recognize that EVs were biologically active and played an important role in the communication between cells. That started the race to better understand how they worked and what impact they might have on human health.

Coincidentally, that’s also about the same time Saleem, now 42, started to think about a career in medical research, although her interest in medicine can be traced back to her childhood in Toronto. “My dad wasn’t a scientist, but he had a master’s degree in microbiology, and he worked in the pharmaceutical industry,” says Saleem. “So, he would be watching heart surgery videos (as part of his job) and as a young child, I would be sitting next to him transfixed. He is an extremely intelligent man, and he always told me your career should always be something that interests you, but something that allows you to be independent.”

With that in mind, Saleem attended York University in Toronto. “I thought I was (going to apply) for medical school” she says. But by the time she entered her fourth year, she realized she was more interested in medical and health research, specifically in the field of molecular exercise physiology and kinesiology. Eventually, Saleem would get a Master of Science degree, followed by a PhD in molecular, cellular and integrative physiology at York in 2013. She then completed a postdoctoral fellowship in pediatrics at McMaster University in 2016.

 In 2018, Saleem took a position as an assistant professor in the Faculty of Kinesiology and Recreation Management at the University of Manitoba. Concurrently, she also accepted an appointment as principal investigator at the Children’s Hospital Research Institute of Manitoba (CHRIM), where her research laboratory is situated.

Since arriving in Winnipeg, Saleem has received about $1.8 million in direct support for her research from various agencies, including Research Manitoba, Natural Sciences and Engineering Research Council of Canada (NSERC), New Frontiers in Research Fund (NFRF), Canada Foundation for Innovation (CFI), CHRIM, and Children’s Hospital Foundation (CHF). Much of her work focusses on the role played by mitochondria, microscopic organelles that serve as the main source of energy for cells. Healthy mitochondria are critical to building healthy cells which are essential to maintaining overall health.

 So, what can we do to help keep our cells functioning at peak capacity? Saleem says exercise is key because it promotes mitochondrial growth. “There are more of them and they work better, that’s a big plus, because there is no medication that can do what exercise does. It will improve your heart, your brain, your liver, your pancreas – every part of your body” says Saleem. She believes that all this positive activity may be facilitated, in part, by EVs.

Ayesha Saleem (front) prepares to isolate extracellular vesicles from a sample in her lab. 

To prove the point, Saleem and her team, (composed of postdoctoral fellows, graduate and undergraduate student researchers, and even high school students), along with various collaborators, recently completed a project that involved taking EVs from a cell culture model of exercise and co-culturing them with other cells.

 The result? “When we put the EVs from one (group) of muscle cells that had been exercised in a petri dish into another (group) of regular muscle cells that hadn’t been exercised, it actually increased their mitochondrial content and function… the more mitochondria, the better the function. This shows for the first time that EVs can transmit (some) of the pro-metabolic effects associated with exercise,” she says.

A paper outlining her research has been accepted by the Journal of Extracellular Vesicles, a top scientific journal in the EV field, and will be published in the near future. But while exercise might be the easiest and simplest way of boosting our mitochondrial health, it doesn’t work for everyone, Saleem says.

 Some people may not be able to exercise while others may have inherited mitochondrial disorders that can cause a range of illnesses and disease, typically beginning in childhood. These conditions include mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), a rare genetic disorder that can affect muscle and the nervous system, Leigh syndrome, a fatal condition that causes nervous system cells to die, or Kearns-Sayre syndrome, a rare disorder that can affect your heart and eyes. Mitochondrial disorders can also leave someone exercise intolerant and can cause a range of health symptoms, including hearing loss, vision loss, poor growth and muscle weakness, just to name a few.

 Complicating things is the fact that some people could have mitochondrial disorders and not even know it. “Sometimes patients don’t know for up to 20 years that they have mitochondrial disorders because it can show up with symptoms that overlap with so many different diseases, and it all depends on which organs are most affected. Your eyes could be affected, your liver function could be affected, your muscles could be affected, your brain could be affected. You could be exhibiting signs that look like diabetes, there is no single marker for diagnosis”.

Saleem is tackling these and other issues through her research, she is currently working to develop a better method for diagnosing mitochondrial disorders, specifically MELAS, using EVs. This work is supported by a Research Manitoba Innovation Proof-of-Concept Grant ($100,000 over two to three years).

“The goal is to find a biomarker, something you can pick up in blood, that you can measure, and you can say, ‘Okay, this person has a mitochondrial disorder, or that this person has MELAS. The theory is that people with mitochondrial disorders like MELAS will have EVs that have a distinct biomolecular signature. You can have different levels of mitochondrial DNA mutations. You can have 10 per cent of the mitochondria DNA with mutation, you can have 20, you can have 40 percent of them mutated, 50 (percent) or even 70 (percent) mutated. The higher the percentage (of mutation), the more chance of the disease showing up early, or showing up with strong symptoms.”- she says.

Saleem hypothesizes the EV biomarker for MELAS will contain biological material(s) that is distinct (from healthy controls) and present in correlation with disease/symptom severity. In addition, she is also working to see if EVs can serve as a potential biomarker for mitochondrial disorders in utero, and whether they might be able to play a role in identifying or treating various forms of cancer.

Looking ahead over the next five years, Saleem says she also plans to build on her most recent research by investigating whether EVs from healthy cells can be used to treat mitochondrial disorders.“You can’t put exercise in pill form. But what if you could focus on mitochondrial dysfunction and see if (exercise-derived) EVs can get us one step closer to identifying the key biochemical messages inside the EVs that we can (then) manufacture synthetically and give to people who can’t exercise but who would benefit from exercise. That’s the long-term goal.” says Saleem.

Dr. Saleem Dr. Saleem is an Assistant Professor in the Faculty of Kinesiology and Recreation Management at the University of Manitoba, and a Principal Investigator at the Children’s Hospital Research Institute of Manitoba (CHRIM). Dr. Saleem currently holds operating grants from SSHRC New Frontiers in Research Fund, Research Manitoba, University of Manitoba and CHRIM.