Dr. Robert Beattie, Dr. Kaarina Kowalec, and Dr. Paul Marcogliese each received $100,000 to advance their groundbreaking research in brain health.

This year, Brain Canada’s Future Leaders program awarded a total of $2.1 million to 21 emerging scientists nationwide, with three of those grants going to researchers from the University of Manitoba (UM).

“Research at Rady Faculty of Health Sciences stands out for its commitment to innovation, interdisciplinary collaboration and community impact,” said Dr. Peter Nickerson, vice-provost (health sciences) and dean, Rady Faculty of Health Sciences.   “We’re thrilled to see Drs. Beattie, Kowalec and Marcogliese honoured with these Future Leaders grants. Their work is at the forefront of brain research, and this recognition not only celebrates their achievements but also underscores the groundbreaking research happening here at the University of Manitoba.”

Dr. Robert Beattie

Beattie, an assistant professor of biochemistry and medical genetics, is working to unravel the mysteries of Rett syndrome, a severe neurodevelopmental disorder that primarily affects girls. “We will use advanced genetic and cellular techniques, similar to using a magnifying glass to closely examine each piece of a puzzle,” said Beattie.

“Just as completing sections of a puzzle gradually reveals the bigger picture, this grant may help us uncover new, personalized treatment options for those affected. The insights gained could also illuminate the mechanisms underlying other neurological disorders, suggesting that solving this intricate puzzle might help unlock mysteries of brain diseases more broadly.”

Dr. Kaarina Kowalec

Kowalec, who is an assistant professor in the College of Pharmacy, is focusing on brain atrophy and cognitive reserve in multiple sclerosis (MS). Kowalec’s project examines how genetic factors, particularly polygenic scores, impact brain health and cognitive decline in people with MS.

“Understanding the role of genetic factors in cognitive reserve can transform how we predict and treat MS,” Kowalec said. “This research has the potential to lead to more tailored and effective treatments, ultimately enhancing patient care.”

Dr. Paul Marcogliese

Marcogliese, an assistant professor of biochemistry and medical genetics,  is investigating the IRF2BPL gene, which is linked to severe brain disorders like NEDAMSS and autism spectrum disorder (ASD). “Our goal is to uncover how changes in the IRF2BPL gene affect brain function and development,” Marcogliese said. “This grant will help us map out potential new targets for treatments, offering hope for those affected by these challenging conditions.”

“People with MS tend to have high rates of psychiatric disorders like depression and anxiety,” explained Dr. Kaarina Kowalec, assistant professor in the College of Pharmacy at the Rady Faculty of Health Sciences, naming just two of the most common comorbidities.

“For most people, when you find out you have MS, you’re at an age where you’re at the beginning of your career or you’re starting your family. The world is your oyster,” said Kowalec. “And then all of a sudden, you’re hit with a big diagnosis, and you don’t know if you’re going to be totally disabled tomorrow or 20 years from now. There’s so much unknown.”

For patients who have a mood disorder like depression alongside their MS – either as a pre-existing condition or one that develops as their MS progresses – it can compound an already difficult situation, both personally and medically.

“Depression has been found to be associated with a faster progression of disability,” Kowalec explained. For researchers like her, that makes it doubly important to learn as much as they can about the causes and connections between the two disorders.

That’s why she’s been exploring the human genome to try to understand which patients have the underlying factors that might contribute to an MS patient developing depression – hopefully before the situation arises.

In a recent paper published in Neurology, Kowalec and a team of researchers from Canada, the USA, and Sweden, analyzed genetic data from a large group of individuals with European ancestry to investigate the relationship between depression and MS.

They used information from individuals in Canada, the UK Biobank, and the USA, totaling 106,682 participants, with some having MS and others serving as healthy controls.

“What we wanted to do with this study was use genetics to see if we can identify people that might have a high risk for depression, hopefully before they have depression,” she said.

By identifying MS patients likely to develop mental health conditions, Kowalec said those patients can be targeted for an early intervention, such as cognitive behavioral therapy.

“There is currently no cure for MS. There are treatments, and they’re getting better all the time, but in the meantime, people need to live their lives,” said Kowalec. “My focus is to find ways to help give people a little peace of mind, help prevent poor outcomes and keep their mental and physical health strong.”

“I’m extremely happy to win this prestigious award,” she said. “It’s an achievement.”

Research Day, which took place earlier this month, gave participants the opportunity to show off the projects they’ve been working tirelessly on. Aboulatta was one of four learners who took part in the invited oral presentation, and 18 participants in the poster competition.

Aboulatta, who received her doctor of pharmacy from Alexandria University in Egypt, is examining the impact that COVID-19 measures and restrictions in Manitoba had on pregnant individuals and perinatal care. She’s working to determine whether adverse perinatal outcomes, like preterm births and stillbirths, can be caused by factors exaggerated by the pandemic measures – like stress, anxiety and socioeconomic factors.

“The actual causes of preterm births and stillbirths have puzzled researchers for decades,” she said. “With the measures that took place during the pandemic, it gives us an opportunity to dig more and find the real causes.”

Aboulatta’s advisors are College of Pharmacy assistant professors Dr. Sherif Eltonsy and Dr. Kaarina Kowalec.

Dr. Luis Perez Davalos won the poster competition at the College of Pharmacy’s Research Day.

For College of Pharmacy master’s student Dr. Luis Perez Davalos, winning the poster competition was unexpected.

“I was trying to really tell a story that portrayed the work we’re doing,” he said. “It went well, and that led to winning the award. I wasn’t aiming for that.”

What Perez Davalos is aiming at is the development of a placenta-on-a-chip model to test nanodrugs to treat preeclampsia, a high blood pressure disorder that can occur during pregnancy. Perez Davalos, who received his medical degree from the National Autonomous University of Mexico, is working to replicate the conditions that happen in preeclampsia in the placenta, but on a chip.

“By creating a placenta-on-a-chip it will possibly accelerate the development of an intervention and instead of taking us 15 years to develop a new drug, maybe we can do it in a third of the time,” he said.

Perez Davalos’ advisor is Dr. Hagar Labouta, an assistant professor at the College of Pharmacy.

“I wish to congratulate the winners of the College of Pharmacy Research Day Presentation competition,” said Kowalec, who chaired Research Day and helped organize the event. “I would also like to say a warm congratulations to all the students, trainees and postdocs who contributed to an engaging and high level of scholarship during the day’s presentations.”

Research Day was combined with the College of Pharmacy’s annual graduate studies celebration and the Morris D. Faiman Lectureship. Dr. Christine Allen, a professor at the University of Toronto’s Leslie Dan Faculty of Pharmacy, gave the lecture on the technological approaches to accelerate development of advanced drug delivery strategies. Allen is an expert in drug formulation and the co-founder of Nanovista Inc., a company focused on high-precision, image-guided cancer therapy.

Could genetic insight in the form of a patient’s “polygenic risk score” help to predict whether electroconvulsive therapy will be effective for that patient?

That’s the focus of a recent study published in the American Journal of Psychiatry, co-led by Dr. Kaarina Kowalec, assistant professor of pharmacy in the Rady Faculty of Health Sciences at UM.

A polygenic risk score is derived from testing a patient’s DNA. It reflects the patient’s “polygenic liability” for certain disorders, based on the presence of genetic biomarkers.

“There are differences in our genetics that can increase the risk of disorders like depression and bipolar disorder,” Kowalec says. “Scientists are starting to demonstrate that genetic biomarkers can also tell us if someone is more likely to respond to a particular treatment. We can potentially use this information to make patients’ outcomes better.”

The goal of improving patient outcomes has been central to Kowalec’s research. When her mother was diagnosed with multiple sclerosis (MS), she wanted to understand why some people with neurological or psychiatric disorders are more likely to experience poor outcomes.

“I started to realize just how much was unknown about these disorders,” she says. “Over the past five years, I’ve researched severe conditions like schizophrenia and MS that haven’t responded to treatment.”

In movies like One Flew Over the Cuckoo’s Nest, electroconvulsive therapy has been negatively depicted as a treatment for psychiatric disorders. But it can be extremely helpful for people who have been unresponsive to other forms of treatment, Kowalec says.

The electrical current, given to the patient after anesthetic, causes a brief seizure, and that can cause changes to the chemicals in the brain. Patients usually receive the treatment 8 to 10 times before they begin to see improvement.

The remission rate after treatment is fairly low, between 30 and 50 per cent. While it is a safe procedure, it can have negative side effects, such as memory loss.

“Patients may not want to risk the side effects if their genetics suggest they won’t respond,” Kowalec says. “With the polygenic risk score, patients could make better-informed decisions with fewer risks.”

Kowalec, who holds a PhD in genomics and epidemiology, completed a postdoctoral fellowship in Sweden before joining UM in 2019. She co-led the recently published study with Dr. Robert Sigström and Dr. Mikael Landén from Sweden’s University of Gothenburg.

The researchers analyzed more than 2,300 patients in Sweden who underwent electroconvulsive therapy for a major depressive episode and agreed to have their DNA tested via a blood sample.

The results revealed that a higher polygenic risk score for major depressive disorder was significantly associated with a lower chance of improvement after the therapy. “This means that a person who is more genetically prone to severe depression is less likely to respond well to ECT,” Kowalec says.

On the other hand, being genetically prone to bipolar disorder was associated with greater improvement after ECT. The study found no relationship between polygenic liability for schizophrenia and the effectiveness of the treatment for a major depressive episode.

The researchers hope to expand the project to study patients’ responses to ECT worldwide. They would also like to examine the relationship between polygenic risk scores and other forms of psychiatric treatment.  

“Based on certain genetic markers, health-care professionals could stratify patients into those more likely and less likely to respond to a certain treatment,” Kowalec says. “This could help patients get the treatment that works best for them much sooner, without trying a number of ineffective therapies.”

And before the Eastland even left the wharf, the lifeboats caused it to list, and then it capsized so quickly that one reporter said it rolled over like “a dead jungle monster shot through the heart.” Eight hundred and forty-four passengers died, a passenger death toll higher than the Titanic’s.

What was meant to save lives, ended up harming and killing many others. Indeed, in 1638, scientist Galileo Galilei warned in his final book that cautionary measures can in turn cause disaster.

When the COVID-19 virus first moved across the globe, governments quickly implemented lockdowns and social distancing rules. As supply chains broke, they worried about material shortages, including prescriptions drugs, and so enacted precautionary measures. In Canada, for instance, some patients received a one-month refill rather than the usual three-month extension. Factors such as this, and the general fear people have of contracting the virus in medical facilities, has changed how people are using the health care system, but we don’t know exactly who is being affected, or how. That, however, is about to change.

“A UM team led by assistant professor Christine Leong in the College of Pharmacy is starting a novel study to see if our cautionary measures are enabling a disaster somewhere else.”

Thanks to the anonymized administrative health data held in the Manitoba Centre for Health Policy (MCHP) at the University of Manitoba (UM), a UM team led by assistant professor Christine Leong in the College of Pharmacy, is starting a novel study to see if our cautionary measures are enabling a disaster somewhere else. We need to know because more pandemics are inevitable.

Christine Leong

Leong and her collaborators received $100,000 in funding from the Research Manitoba COVID-19 Rapid Response Grant to study the changes in med­ication dispensation, health service use (physician visits, hospital visits, emergency department visits), and death rates before—and during—the COVID-19 pandemic in the general population, and in those with a history of mental illness. And in Manitoba, the latter category holds a lot of people: A past UM study found that 28 per cent of our population (or roughly 300,000 individuals) has been diagnosed with a mental disorder within the last five years. So, the potential impact of these restrictions on our society is enormous.

“Obviously a lot of things have changed since COVID happened, and the ways in which people can access in-person health care has shifted, and visits to the Crisis Response Centre for example has gone down. Where are these individuals going? I felt like these changes are a very important area that needed to be looked at,” Leong says.

“I’ve done research in the past looking at health service use and psychotropic medication use in the general population. I was also a primary care pharmacist, working at the Family Medical Centre from 2014 up until it closed in 2019. And I’ve encountered many patients struggling with mental illness, and sometimes the resources available to them are quite limited. So when COVID-19 happened, I was quite interested in studying this further,” she says.

Leong and her team will use the rich data contained within MCHP to see the real-world effects the pandemic has had on those with a psychiatric diagnosis, and the general population.

A key aspect of this study is that it focuses on data from the past five years, including the four years leading up to the pandemic. This enables the research team to establish a solid baseline pattern—which is helpful to policy-makers concerned with everyday planning—and then see how things change during the pandemic, which is key information we need to prepare for the next pandemic. We need to know where to direct resources, both during, and after pandemics: when restrictions lift, people may flood into the system again, potentially creating new resource problems.

James Bolton, a professor of psychiatry at UM, has used MCHP data in other studies and is excited to be collaborating on this specific project.

“I think there’s huge potential for this study to really uncover a lot of important information about how the pandemic is influencing mental health,” he says. “The early signs are that people with mental illnesses are facing unique challenges during the pandemic. And so I think this study is extremely important to take a look at what happens with people’s medication use and their connections with services, to really see what the impacts of COVID are on mental health. And it’s hard to anticipate which direction things will go.”

“I think there’s huge potential for this study to really uncover a lot of important information about how the pandemic is influencing mental health.”

It’s possible the distress caused by social isolation is leading to more people seeking help. Or, the opposite: Because of COVID restricting our ability to connect, people might be avoiding treatments and not renewing prescriptions.

“I think this study will give us a story as to where vulnerable people are going and how they are impacted,” Leong says. “Even before the pandemic, how were they doing? I think this study is going to give us a clearer idea of how we can better care for these patients. This data will let us dig deeper into seeing how can we actually support these patients, whether we are in a pandemic or not.”

Population-level effects

The coronavirus disease 2019 (COVID-19) pandemic is anticipated to have both short-and long-term effects on the mental health and wellbeing of individuals at a population level. Physical distancing, changes in financial circumstances and fears associated with the virus itself can impact mental health. Understanding the psychiatric effects of COVID-19 has become an important research priority. Many shifts in the way individuals access care have occurred.

Using health data from Manitoba, Leong and her team are studying changes in medication adherence, health service use and death rates before and during the COVID-19 pandemic in the general population and in those with a history of mental illness. This study will help us under­stand how the healthcare system can help individuals living with mental illness.

Leong’s team includes collaborators at the Rady Faculty of Health Sciences: Silvia Alessi-Severini, James Bolton, Daniel Chateau, Joseph Delaney, Sherif Eltonsy, Murray Enns, Jamison Falk, Kaarina Kowalec and Jitender Sareen.

Preventing Unintended Disaster is one of the feature stories in the Winter 2021 issue of ResearchLIFE magazine.

“The rates of IBD in Canada are among the highest in the world,” says lead author Heather Carney, a third-year pharmacy student, who was supervised by Dr. Kaarina Kowalec, assistant professor, College of Pharmacy, Rady Faculty of Health Sciences. “Separately, IBD and substance use disorder have a significant impact on quality of life. Our research is among the first to investigate substance use disorder in IBD and provides a foundation for future research of the burden and harms of comorbid IBD and substance use disorder.”

IBD is an inflammatory condition, encompassing ulcerative colitis and Crohn’s Disease, where the body launches inflammatory responses against the gastrointestinal tract, resulting in symptoms such as severe diarrhea, abdominal pain, weight loss and fatigue.

The study, conducted by Carney through a College of Pharmacy-funded Undergraduate Summer Research Award, also identified that people with IBD and who are men, smokers, those who have past or current anxiety disorders, and those with more pain are at greater risk for experiencing a substance use disorder.

For the study, Carney evaluated the prevalence and risk factors of substance use disorders in those with IBD using data collected from 247 individuals in Manitoba with IBD, recruited as part of a larger study investigating psychiatric comorbidities in immune-mediated inflammatory diseases.

Carney says that while it has been established that there is a strong association between IBD and several psychiatric disorders, including depression, anxiety and bipolar disorder, there was minimal prior research of the association between substance use disorder and IBD.

Carney says they hope to see more resources allocated for prevention and harm reduction to help decrease the burden of substance use disorder in those with IBD as well as in the general population. She also hopes to see future research on the effect of substance use disorder on outcomes in IBD, which are still unknown.

“The prevalence of substance use disorder in those with IBD suggests an opportunity for screening and targeted interventions. We know substance use disorder can have a profound effect on the individual and the community – including issues at school or work, relationship difficulties, behaviour changes and legal problems,” she says.

The study’s co-authors are University of Manitoba faculty members/researchers Ruth Ann Marrie, MD, PhD; James M. Bolton, MD; Lesley A. Graff, PhD; Charles N. Bernstein, MD; Kaarina Kowalec, PhD and University of Calgary faculty member Scott B. Patten, MD, PhD.

Kowalec’s findings point to new insights into our understanding of treatment resistant schizophrenia. Kowalec’s study, using large national population-based data from Sweden, found that lower premorbid intelligence scores (premorbid meaning it is measured before schizophrenia was diagnosed) in males and a high occurrence of schizophrenia in a person’s family history were significantly associated with treatment resistant schizophrenia. The study also found that an individuals’ genetic information was not associated.

“For the first time in a large, nationally-representative population, we found that those with schizophrenia, who have multiple family members with schizophrenia or have a low intelligence score, were at high risk for failing drug treatment,” said Kowalec, an assistant professor at the College of Pharmacy at the Rady Faculty of Health Sciences and Affiliated Researcher at the Karolinska Institute (Stockholm, Sweden).

Kowalec’s study aimed to understand the clinical, demographic, and genetic factors associated with treatment resistant schizophrenia by using a Swedish national population sample of 24,706 people and a subgroup of 4,936 people who provided genetic samples.

The clinical, social, and economic burden of treatment resistant schizophrenia are substantial. Kowalec hopes that her findings will have both clinical and research impacts.

“Antipsychotic drug therapies can be very effective for schizophrenia; however, we have identified a group of individuals who may benefit from receiving more targeted or stronger drug therapies earlier on,” said Kowalec.

The research groups’ finding of lower intelligence in treatment resistant schizophrenia will be important in efforts to design novel drug treatments improving cognition in schizophrenia. Their finding of a strong schizophrenia family history being associated with treatment resistance means that its either an individual’s genetics or environment that play a strong role in treatment resistance.

Kowalec hopes this work will help guide future research into this severe and chronically ill group of people.

“This work also points us to future research into understanding the shared genetic and environmental risks for treatment resistance in schizophrenia, including more comprehensive genetic markers,” said Kowalec.

This work was supported by the European Union’s Horizon 2020 Research and Innovation programme under the Marie Skłodowska-Curie grant agreement and from the Government of Canada Banting Postdoctoral Fellowship Program (both to Kaarina Kowalec).

This work is also supported by the Swedish Research Council (to Patrick Sullivan) and National Institute of Mental Health (to Patrick Sullivan). Patrick Sullivan is the senior author on the study.

Kowalec, a new assistant professor in the College of Pharmacy, chose a research path focused on multiple sclerosis (MS) and psychiatric illnesses in part because her mother has MS, and others in her life have had mental health issues.

“It’s important to understand who these people are, what they live with on a regular basis and how we can improve their quality of life,” she says.

Kowalec is interested in personalized or precision medicine – the cutting-edge idea of tailoring treatment to the individual, based on their genetic profile and risk factors. Genomics – the study of genomes – as well as biostatistics and epidemiology play roles in her multi-disciplinary research.

The professor and her lab team are analyzing population-based health data and genomic data to learn how to identify patients with MS or psychiatric disorders who are at high risk of experiencing poor outcomes.

For a person with MS, a poor outcome can be a serious adverse reaction to a drug. Kowalec has previously published on how a particular genomic variant is associated with drug-induced liver injury in MS patients.

She is currently co-investigator for a study of genomic variants that make some MS patients more susceptible to lymphopenia (an abnormally low level of a kind of white blood cell) caused by the drug dimethyl fumarate. The study is funded by a National Multiple Sclerosis Society grant of $64,020.

For a person with schizophrenia, a poor outcome can mean that the illness is poorly controlled, leading to long hospital stays or suicide. Kowalec compares the data for patients who have poor outcomes with that of patients who have better outcomes.

The end goal of her MS research is to one day have people with the disease give a saliva sample for genetic analysis, and a few days later find out whether they are likely to have a serious reaction to a particular drug.

Patients with schizophrenia would find out from a saliva test whether they are genetically likely to be treatment-resistant, so doctors could follow them more closely and they could be placed on more intensive drug treatment.

“I really don’t want to do research that’s only going to be one line in a textbook,” Kowalec says. “I’m not into doing research for the sake of science – it needs to help someone.”

Beyond schizophrenia, she is interested in why drugs just don’t work well for some psychiatric patients. “Between 30 and 60 per cent of people with psychiatric illnesses respond poorly to therapy,” she says.

“Schizophrenia, major depressive disorder, bipolar disorder and anorexia nervosa often run in families and have overlapping genetic architectures. I want to identify the genetic, clinical and demographic risk factors associated with poor outcomes in these disorders.”

Kowalec, who was born and raised in Winnipeg, started her MS research while earning her PhD in pharmacogenomics and pharmacoepidemiology at the University of British Columbia.

Her schizophrenia research began while she was a CIHR Banting Fellow and European Commission Marie Sklodowska-Curie Actions Fellow in medical epidemiology and biostatistics at the Karolinska Institute in Sweden.

After living in Stockholm for two years, Kowalec says she misses the Swedish tradition of fika, a daily break for coffee and a sweet treat with friends or coworkers. But she’s excited to be back at the U of M, where she earned her bachelor’s in microbiology in 2008 and her master’s in medical microbiology in 2011.

“I always wanted to come back here,” she says. “I’d done my master’s here, so I knew the quality of the research I did was identical to the quality of research I did in other places. I really like the size of U of M, and in my experience, people here are trained to the same rigorous level as at the larger universities.”