The study, published in Nature Cell Biology, was the work of a high-powered team including Dr. Brad Doble, associate professor of pediatrics and child health at the Max Rady College of Medicine and the Bihler Chair in Stem Cell Research, and colleagues Michael Taylor and Tamra Ogilvie at Baylor College of Medicine, Houston, Texas.

Multiple UM labs were also supported the research including Central Animal Care Services, the Small Animal and Materials Imaging Core Facility and the Manitoba Centre for Proteomics and Systems Biology.

“The type of brain cancer I’m studying is called medulloblastoma,” explained Doble. “It’s rare but is the most prevalent of pediatric brain cancers, accounting for nearly 20 per cent of all pediatric cancers.”

Medulloblastoma occurs in the cerebellum, a part of the brain located at the base of the skull, responsible for co-ordination and motor functions. Symptoms can include intense headaches, balance problems, difficulty with movement, nausea, vomiting and changes in behavior or personality.

One of the critical challenges in treating medulloblastoma is the current approach, which is broad and aggressive. “It involves whole brain and spinal cord irradiation along with chemotherapy, which has devastating side effects in children whose brains are still developing,” said Doble.

Historically, these tumours were categorized based on their appearance under a microscope, but now, with advances in whole genome sequencing, four main molecular subgroups have been identified.

“This is important because all subgroups, despite their molecular differences, have been treated the same way,” he said.

Doble’s lab, however, is working on changing this approach by developing targeted therapies that consider the unique molecular characteristics of each subgroup.

 “This study focuses on Group 3 medulloblastoma, which, despite aggressive treatment, has a five-year survival rate of only about 60 per cent,” he noted, adding previous studies have reported on the significant role OTX2 plays in Group 3 medulloblastoma.

OTX2 is a protein that acts as a transcription factor, which means it helps regulate which genes are turned on or off in cells. In the context of Group 3 medulloblastoma, OTX2 has been found to play a crucial role in the development of the tumour.

Doble and his colleagues investigated how OTX2 interacts with other proteins, specifically RNA splicing factors.

RNA splicing is a process where segments of RNA are cut out and reconnected to create a final messenger RNA (mRNA) that can be translated into a protein. Doble and his team’s research uncovered that OTX2 regulates RNA splicing in a way that promotes tumour growth.

“This was a groundbreaking finding,”  Doble said. “In mice engrafted with human Group 3 medulloblastoma tumours, treatments that interfered with this RNA splicing pathway successfully reduced tumour size.”

The implications of this discovery are profound, said Doble. “It opens up a new avenue for treatments,” he said. “Instead of using broad, toxic treatments, we’re moving towards a more precise, less harmful approach. This could significantly improve the quality of life for children undergoing treatment.”

UM Knowledge Exchange is an important opportunity for UM researchers to share emerging knowledge with members of the public and the wider UM community. UM Knowledge Exchange is hosted by the Office of the Vice-President (Research and International), with support from the UM Learning for Life Network.

Heart disease is a leading cause of death worldwide and in Canada. Heart attack and heart failure can happen at any age, leading to significant impacts to quality of life for patients and their families. New ground-breaking research from UM is seeking to provide specialized supports and treatment for women living with heart disease and explores the genetic roots of cell death to hopefully someday, reverse or prevent heart failure.

Moderator

Dr. Lorrie Kirshenbaum, Director, Institute of Cardiovascular Sciences St. Boniface Hospital, Canada Research Chair in Molecular Cardiology, Professor, Max Rady College of Medicine, Rady Faculty of Health Sciences

Panelists

Dr. Inna Rabinovich-Nikitin, Assistant Professor, Evelyn Wyrzykowski Family Professor in Cardiovascular Sciences, Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Max Rady College of Medicine, Rady Faculty of Health Sciences

Dr. Shuangbo Liu, Assistant professor, Department of Internal Medicine and Department of Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences

Dr. Brad Doble, Associate Professor and Bihler Chair in Stem Cell Research, Departments of Pediatrics and Child Health & Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences

Heart Health and You February 28, 7pm-8:30pm (CDT) at Degrees Diner. UM Knowledge Exchange is a hybrid event with in-person and online options to attend.

Please register by February 23^rd to join the discussion.

Add Heart Health and You to your calendar. Coffee and other refreshments will be provided, and the kitchen at Degrees Diner will be open for specialty coffee and full food service. Parking is available with registration.

Or join us for online viewing 7 pm CDT to watch the live stream. Participate during the live session by asking your questions via email to: Research [dot] Communications [at] UManitoba [dot] ca

The seven-part UM Knowledge Exchange panel-discussion series is ongoing until May 2024. More details can be found on the UM Knowledge Exchange webpage.

The project, led by Dr. Adrian West, a bioengineer and assistant professor in physiology and pathophysiology is supported through the Government of Canada’s New Frontiers in Research Fund (NFRF) – Exploration stream, a fund dedicated to investing in high-risk, high-reward research to support world-leading innovation.

The multidisciplinary research team from the Rady Faculty of Health Sciences also comprises Dr. Joseph Gordon, associate professor of nursing, and Dr. Brad Doble, associate professor of pediatrics and child health (cross-appointed in biochemistry and medical genetics), with additional support from clinical genetic collaborators specializing in rare metabolic diseases.

Support for research to improve discovery of new treatments for rare heart disease is much needed. There are 7,000 known rare diseases affecting more than 3 million Canadians, representing a significant health, economic and social burden. Adding further strain to this challenge, heart tissue samples from rare disease patients are incredibly scarce, resulting in limited understanding of the metabolic and functional changes that lead to heart failure.

To address this knowledge gap, the multidisciplinary team will work with rare heart disease patients to replicate their unique tissue and cells within 3D bioprinted structures.  This UM-led innovation will be accessible to other laboratories to create unique heart tissue structures that will support greater understanding of treatment options. While most tissue engineered heart models aim to create healthy heart muscle, this research is unique in that it will replicate the tissue and stem cells of people with rare diseases to better understand their treatment options.

“With this exploration grant, we now have the opportunity to elevate our technology to create accessible 3D bioprinted heart tissue of patients with rare metabolic diseases,” said West. “The advantage of our research is we can recreate not just the form of a patient’s heart, but also its function in both physiology and disease.”

Co-principal investigator Gordon will have a lead role in the project by overseeing adaptation of existing heart disease models to the 3D bioprinting context. He will also direct metabolic analysis of the bioprinted muscle and administer novel treatments aimed at recovering metabolic function.

“This research will address the critical need to improve the way that rare diseases are studied in order to support customized patient treatments and improve health outcomes in Canada,” said Gordon.

The project is also supported by the expertise of Doble, a stem cell biologist and the inaugural Bihler Chair in Stem Cell Research, whose lab is located on the Bannatyne campus. His extensive experience in stem cell biology will contribute significantly to the project as he will direct all aspects of stem cell culture including growing patient cells and turning them into heart cells.

“This funding will help us disseminate our knowledge across institutions and hospitals in Canada and around the world as we build upon our work at UM,” said Doble.

“We are proud to be home to this bold innovation here at UM,” said Vice President (Research and International) Dr. Mario Pinto. “This funding recognizes the incredible possibilities when researchers take risks and work together across disciplinary boundaries. Through a cutting-edge, multidisciplinary approach, this team will make significant advancements in understanding rare metabolic diseases and finding new treatments to improve patient care both at home and around the world.”

The NFRF 2022 Exploration competition is funding 128 research projects that are bringing disciplines together in novel ways to form bold, innovative perspectives. The competition is administered by the Tri-agency Institutional Programs Secretariat on behalf of Canada’s three research granting agencies: the Social Sciences and Humanities Research Council, the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council.

One research team aims to better understand the lingering condition known as “long COVID” and the other to examine, at the cellular level, how a receptor for the disease-causing virus works.

Long COVID

The post-COVID-19 syndrome that some patients experience – a condition called long COVID – is poorly defined, said Dr. Alan Katz, director of the Manitoba Centre for Health Policy (MCHP) and professor of community health sciences and family medicine at the Max Rady College of Medicine in the Rady Faculty of Health Sciences.

Dr. Alan Katz

“This condition is really brand new, and clinicians just don’t know enough about it,” said Katz, the project’s nominated principal investigator. “I’m hoping that we can shine a light on these long-term effects of COVID-19 in a way that can help people deal with this in the future.” 

When a person visits their family doctor with long COVID symptoms – such as fatigue, shortness of breath or cough – it’s not easy for the physician to diagnose the syndrome because there is no test to confirm it, Katz said.

The goal of the study, which received $202,000 from the CIHR for one year, is to help clearly define the risk factors, determine who is more likely to get long COVID and describe the long-term effects of the syndrome. The researchers want to define the kinds of symptoms people are reporting, determine how frequent those symptoms are and provide guidance around diagnosing the condition.

To do this, they will study anonymized health data from the Manitoba Population Research Data Repository held at the MCHP. The researchers will zero in on patients with a COVID-19 diagnosis and follow them, analyzing whether there is an increase in visits to their doctors and tracking their symptoms.

The project’s other principal investigators are Dr. Lisa Lix, professor of community health sciences and Canada Research Chair in methods for electronic health data quality, Dr. Yoav Keynan, associate professor of internal medicine, and Dr. Alex Singer, associate professor of family medicine.

Viral signal transmission inside cells

Dr. Ruey-Chyi Su co-leads a team that will investigate how the binding of the spike proteins of various coronavirus variants to the host-cell receptor known as ACE2 affects viral spread and mortality rates. 

Dr. Ruey-Chyi Su

Little is known about what happens inside cells when the spike protein engages the receptor ACE2, said Su, a research scientist at the Public Health Agency of Canada and adjunct professor of medical microbiology and infectious diseases at the Max Rady College of Medicine.

“This is a much-understudied area,” Su said. “It’s very exciting for us because this grant allows us to study whether the engagement of coronavirus variants with ACE2 triggers different sets of events inside the infected cells, leading to increased viral replication and influencing the severity of the disease.”

The study, which received $430,000 from the CIHR for one year, aims to profile molecular changes caused by the viral spike protein binding to the ACE2 receptor and to identify the changes that are unique to the spike protein of each variant. These changes will be examined in cells from both men and women to determine whether sex has any influence.

The researchers also want to know if the cells of healthy people respond differently to the virus binding to the receptor than the cells of people with chronic diseases, such as diabetes.

“I believe what we find will open up a lot of questions, like, ‘Why do our cells respond differently during a viral infection, and what determines that difference?’” Su said. “The project will increase our knowledge of what to expect during a viral infection and also provide knowledge that might lead to treatments. It’s really a knowledge-building study.”

Su’s co-principal investigator is Dr. James Davie, distinguished professor of biochemistry and medical genetics. The co-applicants are Dr. Brad Doble, associate professor and Bihler Chair in Stem Cell Research in pediatrics, biochemistry and the regenerative medicine program, and Dr. Sandra Gonzalez-Diaz, Su’s post-doctoral fellow.