“I think these two projects illustrate the diversity of the kinds of projects The Winnipeg Foundation supports, which expand the spectrum of research with high-risk, high-reward initiatives,” says Dr. Peter Nickerson, Vice-Dean (Research) and Distinguished Professor, Rady Faculty of Health Sciences.

Role of endothelial NMDA receptors in glutamate-induced glioma growth

Dr. Chris Anderson, pharmacology and therapeutics professor, Max Rady College of Medicine, and director, Neuroscience Research Program, Kleysen Institute for Advanced Medicine, leads a team that will further research into glioblastomas, a deadly form of brain cancer with few treatment options and a median survival time of less than 15 months.

Along with co-leads Dr. Tanveer Sharif, department of pathology, and Dr. Ji Hyun Ko, department of human anatomy and cell science, Anderson will study whether a specific cell protein in the lining of brain blood vessels called an NMDA receptor, represents a viable new target for comprehensive therapeutic investigation.

“Dr. Sharif’s collaboration with McMaster University gives us access to patient glioblastoma samples, which we can study in Manitoba,” Anderson says. “We will culture the glioblastoma cells with brain endothelial cells to study the nature of molecular interactions between them, in detail, including the role of NMDA receptors. It’s kind of a simple approach, but it will be effective in allowing us to determine the role NMDA receptors play in glioblastoma cell movement and tumour expansion.”

The second part of the project will involve studying the development of tumours after transplanting patient-derived glioblastoma samples into live mice. 

“Using MRI and PET imaging, as well as other state-of-the-art approaches, we will look at patterns of glioblastoma cell infiltration, as well as tumour size, blood flow and metabolism. Performing these experiments in mice genetically engineered to eliminate NMDA receptors in endothelial cells will allow us to directly test the role of this intriguing host target,” says Anderson.

Big data in mother-infant health research

Dr. Sherif Eltonsy, assistant professor in the College of Pharmacy, was also awarded $100,000 grant, for a multi-site project that will create a national database on the effects of medications on mothers and their offspring.

“The idea is to use real-world data to inform mothers, policymakers and physicians on the effects of medications; which are the safest to use and which pose a risk to mother or infant health,” Eltonsy said. “Pregnant women are excluded from randomized trials, so often this becomes the only way to assess the safety of most medications in the market on mothers and infants.”

Eltonsy, a pharmacoepidemiologist with an academic focus on drug safety, leads the project with two researchers from the Max Rady College of Medicine, Dr. Marcus Ng and Dr. Chelsea Ruth, who specialize in neurology and neonatology respectively. The team is collaborating with researchers in Quebec, Saskatchewan and Alberta.

“The project aligns perfectly with The Winnipeg Foundation Innovation Fund as an interdisciplinary innovative project with short-term tangible outcomes – answers to questions mothers have about how best to keep themselves and their newborns safe – as well as a sustainable long-term platform that can be used regularly for big data analyses in mother-infant health,” Eltonsy said.

During the next year, Eltonsy’s team will focus on creating the infrastructure of the project and developing a pilot demonstration using epilepsy medications data. “We plan to create a national epilepsy and mother-infant health group covering over 1.5 million pregnancies and 20 years of follow-up,” he said.

The two grants are part of The Winnipeg Foundation’s $1-million commitment, over five years, to support cutting-edge medical research projects through the Rady Faculty of Health Sciences at the University of Manitoba.

Stobart [B.Sc.(Hons.)/06, PhD/12] sets the scene, explaining that the lights are astrocytes. They’re a type of glial cells – the supporting cells of the nervous system – not celestial bodies. “They do look a lot like stars, though,” she laughs.

The video shows a live mouse brain responding to stimulus, precisely targeted and highly magnified. The cells have been treated to fluoresce when they sense a particular chemical, calcium.

And the twinkling? That’s when the brain cells she’s targeting are activated. “They’re releasing the chemicals that signal to the next cell,” Stobart says. When the sensors fluoresce, that’s when the secrets of the brain’s universe are revealed.

Stobart, an assistant professor in the College of Pharmacy, once thought she’d like to be a high school teacher. With an easy manner and the ability to make even the most complex ideas come to life, she’s a natural for the classroom.

But while earning her bachelor’s degree, she fell in love with research – specifically, the unexplored reaches of the brain.

Stobart worked in three different labs during her time as a U of M undergraduate, including the National Microbiology Lab, where she studied mad cow disease. That’s where she first encountered astrocytes. “I really became fascinated because there’s so much that we don’t understand about these cells,” she says. Not only did the opportunity fire her curiosity, it also helped solidify her professional ambitions. “I experienced firsthand what research life was like,” she says.“We have the freedom to ask big questions that could potentially redefine our views of the brain or brain disorders, but we must also be tenacious because our ideas and experiments don’t always go to plan.”

After a term studying with Christopher Anderson [PhD/98], director of the U of M’s neuroscience research program, Stobart was hooked. She completed her PhD in pharmacology with Anderson, then went on to a postdoctoral fellowship in Zurich, Switzerland.

In the spring of 2018, she joined the College of Pharmacy and embarked on a career that gives her both time in the classroom and a lab to pursue her research. “It’s the best of both worlds,” she says.

Born in Moose Jaw, Sask., Stobart and her family moved often during her childhood, following her father’s assignments as an RCMP officer. She has lived in Winnipeg the longest and now considers the city home.

As her research unfolds, it seems that one discovery always leads to new avenues of exploration. “I’m applying a lot of the tools used to study astrocytes to now look at pericytes,” says Stobart, referring to another type of brain cell. “I’m trying to study how these cells regulate what the neurons are doing in the brain and how this changes in disease.”

She has received a two-year grant from Research Manitoba of $65,000 per year to study pericytes.

When she has deepened her understanding of cellular activity in the brain, Stobart plans to shift her focus to treatment. “I’m an astrocyte biologist, but I’m also a pharmacologist,” she says. “My long-term goal is something tangible – developing drugs to target cells and to treat disease.”

She’s not thinking small, either. She’s interested in conditions that are impacted by damage or loss to the pericytes and astrocytes – that’s major illnesses like Alzheimer’s disease and stroke.

“The neuroscience community is only just beginning to consider astrocytes and pericytes in disease. It wouldn’t surprise me if ultimately, my research could be applied to a number of different brain disorders where these cells have been the missing link.”