Dr. Lisa Lix, professor of community health sciences and a UM Canada Research Chair in electronic health data quality, and Dr. Ryan Zarychanski, professor of internal medicine and the Lyonel G. Israels Research Chair in Hematology, are among the 49 new CAHS fellows for 2024.  

“Congratulations to Drs. Lix and Zarychanski,” said Dr. Peter Nickerson, UM vice-provost (health sciences) and dean of the Max Rady College of Medicine. “As a CAHS fellow myself, I welcome your expertise and enthusiasm to this Canada-wide group of accomplished scientists and scholars working to advance the health of Canadians and people around the world.”  

Dr. Trevor Young, president of the CAHS, said that election to the Canadian Academy of Health Sciences acknowledges outstanding contributions to the health sciences.  

“We are proud of these Fellows’ accomplishments, and we are honoured to welcome them to the Canadian Academy of Health Sciences,” Young said. 

Lix is an international leader in statistical and data science methods for population-based electronic health data. She is working on improving chronic disease prediction models and collaborates with such organizations as the Public Health Agency of Canada on chronic disease surveillance methods.  

She is the recipient of the Lifetime Achievement Award from the Canadian Society of Epidemiology and Biostatics and is a fellow of the American Statistical Association. Lix provides national leadership to train the next generation of scientists on artificial intelligence in public health.  

Lix said she is thrilled to be inducted into the Canadian Academy of Health Sciences.  

“While it is an honour to be recognized for my leadership and accomplishments in the health sciences, I also recognize that there is a responsibility for ongoing and continued commitment to the Canadian Academy of Health Sciences to contribute my expertise on health-related topics that are of importance to all Canadians,” Lix said.  

Zarychanski’s research focuses on the hematologic aspects of critical illness and he leads several national and international randomized trials in the fields of sepsis, anticoagulation and blood conservation.  

Throughout the COVID-19 pandemic, Zarychanski and team developed novel clinical trial methods to speed knowledge generation and facilitate global collaboration. These adaptive platform trials identified several effective therapies for hospitalized patients to improve survival and prevent illness progression that have been widely adopted in Canada and around the world.  

Zarychanski, who is also a researcher with CancerCare Manitoba, said it is a tremendous honour to be inducted into the CAHS and it speaks to the supportive scientific environment at UM and CancerCare Manitoba that helps support world-class science and made-in-Manitoba discoveries.  

“While the goal of the research and clinical trials our local team undertakes squarely focuses on improving patient outcomes and the function and sustainability of our health system, external validation of the team’s commitment and impact is energizing,” Zarychanski said. “With the decorated fellows in the academy, I look forward to promoting clinical trials in health research as one core component of a learning health system.” 

View the list of UM CAHS fellows.  

On Nov. 18, UM alumni, partners, faculty members, students and friends of the college will celebrate the 140th anniversary at a gala at the RBC Convention Centre. The event will raise funds for MD and grad student bursaries.

While the medical college has educated generations of physicians and served the community, it has also been a thriving centre for the advancement of medical science.

“We’re known for punching above our weight in terms of our research achievements,” says Peter Nickerson [B.Sc.(Med.)/86, MD/86], vice-provost (health sciences) and dean of the Max Rady College of Medicine and the Rady Faculty of Health Sciences.

“Each year, the college brings in more than $100 million in external research funding. Our investigators, including master’s and PhD students, conduct multidisciplinary research that influences health policy, improves patient care and saves lives.”

From innovative disease research carried out in labs and at hospital bedsides, to studies that give a voice to under-represented patient groups, to findings gleaned from one of the world’s richest storehouses of health data – the Manitoba Population Research Data Repository – the Max Rady College of Medicine is constantly generating new knowledge.

“Our strengths include being exceptionally collaborative, forging effective external partnerships and reaping the benefits of intergenerational chains of research mentors and mentees,” says Nickerson, a kidney specialist who is himself a distinguished research scientist.

In addition to the acclaimed faculty members and alumni who are laureates of the Canadian Medical Hall of Fame – we’re spotlighting them in a list on Nov. 16 – here are 10 Max Rady College of Medicine research highlights that have made an indelible impact.

Dr. Lorrie Kirshenbaum

• In 1948, a cardiologist convinced nearly 4,000 air force veterans to enrol in a study of their cardiovascular health. The extraordinary project, based at UM and known as the Manitoba Follow-up Study, is one of the world’s longest-running health studies of a specific cohort. One of its findings in the 1990s was that shorter men are at greater risk of dying of heart disease than taller men. The study, now led by Robert Tate [M.Sc./75, PhD/00] and marking 75 years, is still tracking a handful of surviving participants. Meanwhile, UM scientists like Lorrie Kirshenbaum [B.Sc./86, M.Sc./88, PhD/92], Canada Research Chair in molecular cardiology, are engaged in leading-edge cardiovascular research. Kirshenbaum has earned international recognition for his work on cardiac cell death and its impact on the development of heart failure.

Dr. Edward (Ted) Lyons

• In the mid-1960s, UM radiologist Edward (Ted) Lyons [B.Sc./63, B.Sc.(Med.)/68, MD/68] became one of the earliest pioneers of ultrasound. His groundbreaking research helped to establish ultrasound as safe for fetuses and mothers, and his findings influenced hospitals across the globe to adopt the technology. Lyons led the first lab in Canada to perform general ultrasound. For years, he worked with manufacturers to evolve the technology from a machine the size of a refrigerator to a portable device no larger than a cellphone. He has called himself “a traveller on a stream of new imaging technology.”

Dr. Stephen Moses

• Frank Plummer [MD/76], who passed away in 2020, was a key member of a multigenerational chain of researchers who have worked for more than 40 years in partnership with the University of Nairobi, making high-impact discoveries in the area of sexually transmitted infections. In the late 1980s, Plummer led a UM team in discovering that some Kenyan women sex workers who had been exposed to HIV infection were naturally immune to it. This breakthrough provided vital new information for HIV vaccine and drug development. In 2007, UM’s Dr. Stephen Moses co-led a study showing that circumcision reduced the risk of HIV infection by 50 to 60 per cent in men who had heterosexual sex. This insight was named one of the biggest medical breakthroughs of the year by Time magazine.

Dr. Heather Dean

• In the late 1980s, when Type 2 diabetes was considered an adult-only disease, UM pediatric endocrinologist Dr. Heather Dean and her colleagues made the startling discovery that some First Nations children in Manitoba and northwestern Ontario had the disease. They published the first paper about these children in 1992. Dean went on to work closely with First Nations communities to better understand the disease. Today, UM researchers continue to study many aspects of youth-onset Type 2 diabetes, including following a cohort of offspring of First Nations individuals who were first diagnosed as children.

Dr. Ryan Zarychanski (Photo: Doctors Manitoba)

• In 2012, a breakthrough by UM and CancerCare Manitoba scientists made the cover of Blood, the world’s top medical journal on blood disorders. The study, led by Dr. Ryan Zarychanski [B.Sc./95, B.Sc.(Med.)/00], identified the genetic mutation responsible for the hereditary blood disorder xerocytosis. Groundwork for this discovery had been laid 40 years earlier by UM hematologist Lyonel Israels [MD/49, M.Sc./50], founding father of CancerCare Manitoba. Zarychanski now holds the Lyonel G. Israels Research Chair in Hematology. This year, he was named Physician of the Year by Doctors Manitoba for leading international clinical research to rapidly assess potential treatments for COVID-19.

Dr. Gary Kobinger

Dr. Jason Kindrachuk

• During the Ebola outbreak in West Africa, UM’s Dr. Gary Kobinger was chief of special pathogens at the Public Health Agency of Canada (PHAC) National Microbiology Laboratory in Winnipeg. His team of UM and PHAC researchers co-developed an experimental antibody cocktail called ZMapp. In 2014, it was used in saving the life of an American doctor with Ebola – a dramatic event that made international headlines. Today, Dr. Jason Kindrachuk, Canada Research Chair in the molecular pathogenesis of emerging viruses, is keeping UM on the map as a virus centre through his work on viruses such as Ebola, mpox and coronaviruses.

Dr. Marcia Anderson

• UM is a national leader in partnering with Indigenous communities in health research. In 2019, for example, a landmark joint study by the First Nations Health and Social Secretariat of Manitoba and the Manitoba Centre for Health Policy in the Max Rady College of Medicine illuminated the worsening health gap between First Nation people and all other Manitobans. This year, UM’s Marcia Anderson [MD/02] took a leadership role in making Manitoba the first province to systematically ask hospital patients to voluntarily declare their race, ethnicity or Indigenous identity. The purpose of collecting this data is to address racial inequities in health care.

Dr. James Blanchard

• In 2022, health research and programming in India led by James Blanchard [B.Sc.(Med.)/86, MD/86], executive director of the UM Institute for Global Public Health, received a major injection of support from the Bill & Melinda Gates Foundation. The funding of US$87 million will support reproductive, maternal, newborn and child health in the state of Uttar Pradesh. In total, the Bill & Melinda Gates Foundation has invested US$280 million in international UM projects. The Institute for Global Public Health has been a world leader in forming partnerships to strengthen health systems and influence health policy, particularly in countries in Asia and Africa, says Blanchard, who holds a Canada Research Chair in epidemiology and global public health.

Dr. Ruth Ann Marrie

• An internationally renowned multiple sclerosis (MS) researcher at UM, neurologist Dr. Ruth Ann Marrie, directs the MS Clinic at Health Sciences Centre. This year, Marrie received a prestigious U.S. prize for her trailblazing body of work. She and her team were the first to explore the implications of comorbidities such as high blood pressure and heart disease in people with MS. She has also shown that the disease may have a “prodromal phase” that precedes the onset of specific MS symptoms. Her ongoing research is laying important groundwork for both prevention and improved treatment of MS.

Dr. Meghan Azad

• Meghan Azad [PhD/10] is a worldwide expert on the science of breast milk. She holds a Canada Research Chair in developmental origins of chronic disease at UM and is also a researcher with the Children’s Hospital Research Institute of Manitoba. This year, she and her team landed a grant of US$2.5 million from a prestigious U.S. funder, the National Institutes of Health. The project will include in-depth lab analyses of milk samples from 1,600 mother-child pairs, looking at breast milk in a way that is unique in the world. The data will then go to machine-learning experts at Stanford University, who will use artificial intelligence to explore it. The study is expected to generate the world’s largest and most detailed dataset of mothers, infants and breast milk.

All nine award recipients for 2023 have connections to the Max Rady College of Medicine at the Rady Faculty of Health Sciences. Five recipients are UM alumni, one is a current resident and seven hold positions with the college, including Physician of the Year Dr. Ryan Zarychanski.

“As a graduate of the Max Rady College of Medicine myself, I’m proud that all nine of the extraordinary physicians winning Doctors Manitoba Awards this year have a connection to the University of Manitoba,” said Dr. Candace Bradshaw, president of Doctors Manitoba.

“This speaks to the value of our university in the medical community and how physicians maintain a connection throughout their careers, whether they graduated from UM or moved here from out of province and forged that connection mid-career.”  

The winners were nominated by their physician peers and selected following an evaluation by a Doctors Manitoba committee. A gala awards celebration will be held this spring.

“Congratulations to the outstanding physicians who received Doctors Manitoba Awards this year,” said Dr. Peter Nickerson, vice-provost (health sciences), dean, Max Rady College of Medicine, and dean, Rady Faculty of Health Sciences.

“I’m thrilled to see that all nine recipients are associated with the Max Rady College of Medicine. This demonstrates the top-notch leaders our medical school develops, and the terrific physicians who work with the college as researchers, clinicians and instructors.”

PHYSICIAN of the YEAR

Dr. Ryan Zarychanski (Photo courtesy of Doctors Manitoba)

Dr. Ryan Zarychanski [B.Sc./95, B.Sc. (Med.)/00], associate professor of internal medicine at the Max Rady College of Medicine, led groundbreaking work during the pandemic to rapidly assess the effectiveness of potential treatments for COVID-19. This work was trailblazing at a global level, both in the treatments identified and the process developed to identify them. By establishing a global network of scientists, Zarychanski raised significant funding, led life-saving clinical studies spanning 104 countries, and developed a new method of conducting and analyzing randomized clinical trials to speed knowledge generation. Ultimately, these trials identified effective treatment options for patients with serious COVID-19 infections.

HUMANITARIAN of the YEAR

Dr. Tamara McColl (Photo courtesy of Doctors Manitoba)

Tamara McColl [B.Sc./07, B.Sc. (Med.)/11, MD/11], director of education scholarship and faculty development in the department of emergency medicine at the Max Rady College of Medicine, is an emergency medicine physician who has dedicated the last year to supporting the Ukrainian community in Manitoba and Ukraine. Her community service and humanitarian work have included leading local efforts to mobilize support through fundraising and rallies while also joining multiple medical relief missions to Ukraine through the Canadian Medical Assistant Teams and Canada Ukraine Surgical Aid Program.

DISTINGUISHED SERVICE

Dr. Maggie Morris (Photo courtesy of Doctors Manitoba)

Dr. Maggie Morris [M.Ed/10), professor of obstetrics, gynecology and reproductive sciences at the Max Rady College of Medicine, has served Manitoba for nearly 40 years as a physician, educator and leader in women’s health. As a clinician, she has dedicated much of her practice to vulnerable patients. She has played a pivotal role in the education of thousands of physicians and physician assistants, using innovative and engaging techniques. As chair of obstetrics, gynecology and reproductive sciences and provincial lead of women’s health, she oversaw major improvements in care and the design of the new HSC Winnipeg Women’s Hospital.

RESIDENT of the YEAR

Dr. Alwyn Gomez (Photo courtesy of Doctors Manitoba)

Dr. Alwyn Gomez, a medical resident and PhD student in the department of human anatomy and cell science at the Max Rady College of Medicine, is an exceptionally talented resident physician specializing in neurosurgery. He has a passion for research and his PhD work is focused on traumatic brain injury. He is also strongly dedicated to supporting medical education, helping to develop new programming in dissection and showcasing Manitoba’s postgraduate medical education program to prospective learners.

MEDALS of EXCELLENCE

Dr. Biniam Kidane (Photo courtesy of Doctors Manitoba)

Dr. Biniam Kidane, assistant professor of surgery at the Max Rady College of Medicine, is a thoracic and foregut surgeon and clinician-scientist. He is the medical director of the Wilf Taillieu Thoracic Surgery Endoscopy Unit. He is recognized for his constant dedication to his patients, along with his pioneering work to maintain care during the many disruptions to surgical and hospital services through the pandemic, including for lung and esophageal cancer patients. Guided by Kidane, Manitoba has become a leader in minimally invasive thoracic surgery and interventional endoscopy, which has resulted in shorter recovery times and better outcomes for patients.

Dr. Courtney Leary (Photo courtesy of Doctors Manitoba)

Courtney Leary [B.Sc./04, MD/08], who completed her MD degree and family medicine residency at UM, is the first physician to be raised in and now serve the people of Norway House Cree Nation. She is now the chief of staff for Norway House Hospital and Clinic, and her leadership was pivotal to the development of the new Health Centre of Excellence. Her deep roots and commitment to her community were vital during the pandemic, when she found innovative ways to ensure health care was available, delayed the arrival of COVID-19 in the community, and built relationships that were pivotal to achieving a high level of vaccine uptake.

Dr. Katherine Kearns and Dr. Christina Raimondi (Photo courtesy of Doctors Manitoba.

Dr. Katherine Kearns, who completed her medicine residency at UM and is an assistant professor of family medicine, and Christina Raimondi [B.Sc./00, MD/04], a lecturer at the Max Rady College of Medicine, together established the Winnipeg Breastfeeding Centre in 2017, responding to the overwhelming challenges many patients had in accessing help with lactation or infant feeding. Using the latest scientific evidence on breastfeeding, human milk feeding and infant feeding practices, the clinic and its experts are now trusted resources for patients and physicians. Kearns and Raimondi achieved all of this while maintaining their regular clinical practices.

Dr. Michael Loudon (Photo courtesy of Doctors Manitoba)

Dr. Michael Loudon, a clinical teacher at the Max Rady College of Medicine, is a champion for physician health. While maintaining his rural family medicine practice, he spent 15 years leading physician peer support programming and helping to destigmatize substance use disorders. His work helped physicians regain their health and continue to practise. He has also been a pivotal member of several physician health initiatives, including efforts to tackle the systemic and organizational causes of physician burnout and distress.

With files from Doctors Manitoba

Dr. Lauren Kelly, assistant professor of pharmacology and therapeutics, and community health sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, has received $4.9 million over three years from the Canadian Institutes of Health Research’s (CIHR) Clinical Trials Fund to create educational and mentoring opportunities for doctoral, postdoctoral and early career researchers and clinicians.

Dr. Lauren Kelly

The training platform, called Increasing Capacity for Maternal and Paediatric Clinical Trials (IMPaCT), will bring together more than 50 mentors and 20 clinical trial teams from across Canada and will launch at www.IMPaCTrials.ca in a few weeks.

“We need more people with the skills, expertise and passion to do clinical trials in the areas of pediatric and pregnancy, and this platform will help address that,” said Kelly, who is also the clinical trials director at the Children’s Hospital Research Institute of Manitoba, and a clinical trialist at the George & Fay Yee Centre for Healthcare Innovation. “My goal is that by the end of the three years, we will have a strong network for pediatric and pregnancy trials across Canada. The best way to build that is together.”

IMPaCT will have three major components. The first is an online component with open-access training available to anyone interested in learning about clinical trials. The second component is a fellowship program, which will include up to 60 fellowship opportunities. The third component is a summit, which will include a four-day professional development program and will focus on areas like grant writing, career mentorship and designing protocols.

Dr. Peter Nickerson, vice-provost (health sciences), dean, Max Rady College of Medicine, and dean, Rady Faculty of Health Sciences, said he is eager to see the launch of IMPaCT.

“IMPaCT will provide enthusiastic trainees with the knowledge and skills needed to run their own clinical trials in the future,” Nickerson said. “Expanding the number of individuals with clinical trial training in the areas of pregnancy and pediatrics is critical to advance patient care in these areas.”

IMPaCT will also develop a government advocacy program for five fellows and three mentors to learn how to work alongside the government to advocate for more investments in child health and pregnancy research.

“Clinical trials are complicated. There’s lots of paperwork, daunting words, government regulation and liability, so it can be a scary place,” Kelly said. “Our vision is to demystify this process and connect people so they’re supported to enter careers in clinical trials. That’s something I never had when I started, and I now have the opportunity to design the training program I wish I had when I was a trainee.”

Kelly plans to work alongside the newly CIHR-funded Accelerating Clinical Trials (ACT) Consortium to further build the capacity for clinical trials with pregnant people and children from across Canada. The ACT-Consortium was awarded more than $38 million to strengthen coordination between domestic and international clinical trial networks. Kelly and Dr. Ryan Zarychanski, associate professor of internal medicine, Max Rady College of Medicine and senior scientist at CancerCare Manitoba, are principal applicants and the Manitoba representatives for ACT-Consortium.

“This excellent showing by our faculty members and their partners in receiving this funding is a testament to the outstanding quality of research conducted at the University of Manitoba,” said Dr. Mario Pinto, UM’s vice-president (research and international). “I congratulate these research leaders, whose work continues to improve the quality of health and patient care here in Manitoba and around the world.”

Project: Anti-Thrombotic Therapy to Ameliorate Clinical Complications in Community Acquired Pneumonia (ATTACC-CAP)

Dr. Ryan Zarychanski and Dr. Sylvain Lother

Dr. Ryan Zarychanski, associate professor of internal medicine, Max Rady College of Medicine and senior scientist at CancerCare Manitoba, and his team received more than $3.9 million over five years.

Building on the knowledge the trial team gained while studying the blood thinner heparin in COVID-19 patients, the Manitoba-led team will conduct a large international adaptive randomized trial that will evaluate whether therapeutic-dose heparin reduces critical illness and mortality in hospitalized patients with non-COVID pneumonia.

“This is the first large international trial to be wholly managed by the University of Manitoba and will provide unique training opportunities to junior faculty like co-principal investigator Dr. Sylvain Lother,” said Zarychanski, UM Lyonel G. Israels Research Chair in Hematology. “It will also showcase UM’s clinical trial management and data coordination capacity at the George and Fay Yee Centre for Healthcare Innovation.”

Project: Regulation of Programmed Necrosis in the Heart

Dr. Lorrie Kirshenbaum

Dr. Lorrie Kirshenbaum, UM Canada Research Chair in molecular cardiology and professor of physiology & pathophysiology and pharmacology & therapeutics, Max Rady College of Medicine, and his team received $1.1 million over five years.

The study will focus on the role of mitochondrial-regulated cell death programs and how they integrate at the cellular level to cause heart failure. The study will look at the mechanisms underlying doxorubicin (a chemotherapy drug) cardiotoxicity. It will also explore the relationship between cell death and other cardiovascular diseases, such as heart attack, known to cause heart failure.

“The studies are highly innovative and clinically relevant, as many of the concepts and avenues of research have not been previously explored,” said Kirshenbaum, director of the Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre. “I am particularly excited about commencing this research and hopeful it will be translated into new drug discoveries that will reduce the incidence of heart failure and improve the quality of life of cancer patients and individuals following heart attack or other human diseases where cell death is known to play a major role.”

Project: Understanding the cellular mechanisms that drive clonal T cell expansion of the HIV reservoir

Dr. Thomas Murooka

Dr. Thomas Murooka, associate professor of immunology, Max Rady College of Medicine, and his team received more than $719,000 over five years.

The study aligns with emerging data that a distinct subset of T cells seems to harbour the majority of residual HIV. By understanding why some T cells contain virus and others don’t, it may lead to a more targeted approach to purge this HIV reservoir in T cells. Murooka and his team will use new imaging tools and animal models to identify, track and kill these rare, infected T cells, so that daily drug regimens are no longer required for people living with HIV.

“So far, the HIV cure field has used a sledgehammer approach to eliminate residual HIV infection, with limited success,” Murooka said. “We are developing a more targeted, immunological approach to specifically identify and destroy rare T cells that harbour HIV as a new approach to achieve HIV cure.”

Project: Mechanisms and consequences of senescent beta cell accumulation in Type 1 Diabetes

Dr. Peter Thompson

Dr. Peter Thompson, assistant professor of physiology & pathophysiology, Max Rady College of Medicine, and his team received more than $589,000 over five years.

Thompson’s recent research has discovered that beta cells are not entirely innocent in the process that leads to Type 1 diabetes and some of them may aid and abet the immune attack. In this study, he will explore the “nuts and bolts” of these sick beta cells to determine how and why they arise, and how they may be restored. The research will take him closer to establishing a new early clinical intervention to prevent Type 1 diabetes in people who are at risk.

“Our study is unique in that it is working from a completely different concept of how Type 1 diabetes occurs as compared with conventional wisdom,” Thompson said. “It has generally been assumed that Type 1 diabetes is just an autoimmune disease, where the beta cells are just targets of the immune attack and thus the vast majority of interventional efforts are aimed at restoring the immune system. Until recently, very little attention was paid to processes operating in beta cells that might contribute. So our work is operating from a different point of view – which is that some beta cells actually promote the immune attack, leading to Type 1 diabetes. This is a major paradigm shift in how we understand the disease with implications for developing new therapies and we are now poised to make exciting progress in this area.”

Project: Confronting Homophobia in Anal Health: Community-based Program Science and HPV among MSM in Nairobi, Kenya

Dr. Rob Lorway

Dr. Rob Lorway, UM Canada Research Chair in global intervention politics and social transformation and professor of community health sciences, Max Rady College of Medicine, and his team received more than $512,000 over three years.

Lorway’s project builds on the University of Manitoba’s extensive Kenyan-Canadian collaboration that has been studying sexually transmitted infections since the 1980s. His team will employ new community-based participatory strategies to identify the risk factors that underlie HPV-related anal diseases among gay, bisexual and other men who have sex with men in Kenya. Lorway aims to generate new scientific knowledge related to the clinical, social and epidemiological aspects of HPV infection to inform local sexual health services delivery.

“Although HPV immunization programs in Kenya tend to focus on cervical cancer among adolescent girls and young women, the evidence from this study will enable community health activists and their allied health care providers to advocate for the urgent need to expand immunization to include gay, bisexual and other men who have sex with men,” Lorway said.    

Project: Investigating the molecular and cellular abnormalities of the brain in Rett syndrome

Dr. Mojgan Rastegar

Dr. Mojgan Rastegar, professor of biochemistry & medical genetics, Max Rady College of Medicine, and her team received $100,000 over one year.

The study focuses on the molecular and cellular abnormalities of the brain in a neurodevelopmental disorder known as Rett syndrome. Rastegar and her team will perform side-by-side molecular and cellular research studies to determine the shared anomalies of the human and murine Rett syndrome brains. Her research will further include an investigation of rescue and recovery of the identified Rett syndrome-associated abnormalities, by the application of commonly used drugs in pre-clinical therapeutic studies in animal models of Rett syndrome. 

“Our research results from this project are expected to determine the extent of molecular and cellular damage in the brain of Rett syndrome patients and shared defects with animal models of this disease,” Rastegar said. “Our research may eventually lead to potential therapeutic solutions that are targeted towards commonly impaired characteristics of the brain in Rett syndrome. Our research results may also help to understand the unique characteristics of specific types of MeCP2 mutations for this complex and severe disease. MeCP2 is a protein that binds, reads and interprets genomic modifications.”

Senior author on the studies (Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19 and Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19), Dr. Ryan Zarychanski, associate professor of internal medicine, University of Manitoba, and hematologist, critical care physician and senior scientist at CancerCare Manitoba, Canada, said, “We had an unprecedented opportunity to work with colleagues across Canada, the United States and around the world to test the benefit of full-dose blood thinners on hospitalized COVID-19 patients. Therapeutic heparin improved survival and decreased progression to severe disease, thus reducing the pressure on intensive care units globally.”

The participating trial platforms that contributed to the global trial were Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC); Randomized, Embedded, Multi-factorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP); and Accelerating COVID-19 Therapeutic Interventions and Vaccines-4 (ACTIV-4) platforms. The worldwide multiplatform trial spanned five continents in over 300 hospitals to urgently test blood thinners on both sets of patients.

Early in the pandemic, physicians around the world observed increased rates of blood clots and inflammation among COVID-19 patients which affected multiple organs and led to complications such as lung failure, heart attack and stroke. Whether providing increased doses of blood thinners routinely administered to hospitalized patients would be safe and effective was unknown at that time.

“The goal [of our trials] was to improve survival and prevent patients from requiring ICU-level care or developing multi-organ failure,” said Dr. Patrick Lawler, cardiologist at the University of Toronto and Peter Munk Cardiac Centre at University Health Network, who was co-principal investigator of ATTACC, a member of the international trial steering committee for REMAP-CAP and on the ACTIV-4a protocol development committee.

In December 2020, results indicated that full dose anticoagulation with heparin was not beneficial and appeared to be harmful among critically ill patients – but the findings were completely different in non-critically ill patients. In January 2021, results of the treatment among moderately ill COVID patients showed full doses of heparin reduced the need for life support with improved survival.

Moderately ill patients are defined as hospitalized COVID-19 patients who were not in ICU and who were not receiving organ support such as mechanical ventilation at trial enrollment.

Trial data analysis involved 1,074 critically ill and 2,219 moderately ill patients. Physician investigators gauged how long participants were free of organ support up to 21 days after enrolling in the clinical trial. The investigators discovered that in moderately ill patients full-dose heparin reduced the need for organ support compared to those who received lower-dose heparin. By contrast, for critically ill patients, full-dose heparin was associated with a high probability of a worse outcome.

“Our conclusions have set a new standard of care for moderately ill hospitalized COVID-19 patients around the world using an affordable, accessible and familiar drug. As such the results of the trial can be immediately applied,” said Dr. Ewan Goligher, critical care physician and scientist at Toronto General Hospital, co-chair of the therapeutic anticoagulation domain in REMAP-CAP, co-principal investigator of the ATTACC platform.

“While the trial results will immediately impact care around the world, it is the methods of collaboration created that will be an enduring contribution of this first of a kind clinical trial that paves the way for future multiplatform clinical trial collaborations on a global scale,” said Zarychanski, senior author, chair of the ATTACC trial and the REMAP-CAP anticoagulation domain and member of the ACTIV-4a protocol development committee.

“We were excited to provide leadership on these innovative, large scale clinical trials – especially at a critical time during the COVID-19 pandemic – and our findings demonstrate the value of international multiplatform collaboration and the future possibilities for continuing to study ways to improve health outcomes in COVID-19 and possibly other diseases,” said Lawler.

“It is a testament to the dedication of researchers around the world who worked closely and collaboratively during a very difficult time that we were able to discover a treatment that can prevent patients from becoming severely ill and improve their recovery and outcomes, but our work is not over yet,” added Goligher.

“The Manitoba government is proud to have been an early supporter of this ground-breaking, life-saving research led out of our province,” Manitoba Premier Brian Pallister said. “The $5 million COVID-19 research fund announced last spring through Research Manitoba allowed local clinician-scientists to embed clinical trials into clinical care and collaborate in new ways so that their research findings can have global impact by advancing COVID-19 treatments.”

In Canada, the trials were supported by multiple international funding organizations including Canadian Institutes of Health Research (CAN), LifeArc, the Provinces of Ontario and Manitoba, the Peter Munk Cardiac Centre, the Thistledown Foundation, CancerCare Manitoba Foundation, and the Victoria General Hospital Foundation; trial management and data coordination was provided by Ozmosis Research and Socar Research. Internationally, the trials were supported by the NIH National Heart, Lung & Blood Institute, Translational Breast Cancer Research Consortium and the UPMC Learning While Doing Program (US), National Institute for Health Research (UK), National Health and Medical Research Council (AUS), Health Research Council of New Zealand, and the PREPARE and RECOVER consortia (EU).

The ATTAC trial (antithrombotic therapy to ameliorate complications of COVID-19), is an international multi-platform randomized control trial (mpRCT) led by Ryan Zarychanski, a hematol­ogist, critical care physician and associate professor. He has partnered with Patrick Lawler, at the Peter Munk Cardiac Centre and Ewan Goligher, from the University Health Network, both assistant professors at the University of Toronto.

“The trial is evaluating if therapeutic anticoagulation with heparin will improve clinical outcomes in patients hospitalized with COVID-19,” says Zarychanski, also a scientist at CancerCare Manitoba. “With regard to issues of anticoagulation, our trial will inform best-practice on a global scale.”

Commonly given to hospitalized patients to prevent blood clots, heparins are being studied as a COVID-19 treatment for several reasons. For starters, blood clots have been observed in a significant proportion of patients in hospital with COVID-19.

Manitoba COVID-19 clinical trial team members – Sheri Stein, Emily Rimmer, Hessam Kashani, Nicole Marten, Gary Annable, Maureen Hutmacher, Lauren Kelly, Dayna Solvason, Nora Choi, Maggie Wilson, Brett Houston, Ryan Zarychanski, Glen Drobot. MISSING: Quinn Tays, Soumya Alias, Rhonda Saliva, Terry Wurez, Sylvain Lother, Gloria Vazquez Grande, Amila Heendeniya, Lisa Albensi.

Heparins also possess anti-inflammatory properties, and COVID-19 is associated with inflammation, which can increase the likelihood of venous clots in the legs or lungs, or arterial clots which can cause heart attacks or strokes.

Additionally, heparin has been shown to impair the ability of the SARS CoV-2 virus from binding to the surface of cells and thus may have specific antiviral properties.

“The goal of the trial is not just to reduce blood clots but more importantly to reduce mortality and prevent people from needing ICU level care or developing multi-organ failure,” says Zarychanski.

The trial originated as two separate trials, with ATTACC studying therapeutic anticoagulation in hospitalized moderately ill patients and the Randomised, Embed­ded, Multi-factorial, Adaptive Platform (REMAP) trial studying therapeutic anti­coagulation in severely ill patients. Each trial has since extended their enrolment criteria and harmonized their protocols to form one large trial enrolling all eligible hospitalized COVID-19 patients.

Then, the National Institutes of Health (NIH), a U.S. government agency, decided to adopt the Manitoba-sponsored combined trial across the whole of the U.S. as part of the ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines) platform.

ATTACC, REMAP and ACTIV-IV have now merged to form a novel multiple plat­form RCT with sites in North and South America, Europe, India and Australia.

Dr. Ryan Zarychanski, Max Rady College of Medicine.

The ATTACC/REMAP/ACTIV trial, says Zaryhanski, is a new type of clinical trial strategy: the mpRCT methodology allows inde­pendent networks or platforms to enroll patients using the harmonized protocol and analyze individual patient data as one unified trial.”

This allows patients to be enrolled with great speed so a trial conclusion can be made as quickly as possible.

So far, over 3,000 patients have been enrolled in the mpRCT. The ATTACC platform alone has 58 activated sites with 1,200 patients enrolled in Canada, U.S., Brazil and Mexico. REMAP has enrolled nearly 1,500 patients in Canada, U.S., E.U., U.K., Ireland, Australia, New Zealand and Saudi Arabia. The NIH sponsored ACTIV-IV platform has enrolled approximately 400 patients and is expanding rapidly.

Zarychanski says, “Over 300 sites have been activated in more than a dozen countries and we’ve recently expanded to include sites in low and middle income countries through our REMAP platform.”

“Over 300 sites have been activated in more than a dozen countries and we’ve recently expanded to include sites in low and middle income countries through our REMAP platform.”

“Launching the trial in multiple countries gave us the greatest ability to successfully complete enrollment,” he says.

To action a trial as large as ATTACC, the project team is large and necessarily international. Day-to-day trial management is lead by Lindsay Bond of Ozmosis Research in Toronto, ON who works collabora­tively with Manitoba multi-site project managers Nicole Marten and Dayna Solvason. As the sponsor, UM expertly leads the processes of international contracting and payments.

“The trial is providing exciting opportunities for our local trainees and faculty,” says Zarychanski.

Brett Houston MD (PhD candidate), Gloria Vazquez Grande MD (PhD candidate), Sylvain Lother MD (MSc candidate), Vi Dao MD and Glen Drobot serve as local primary investigators for ATTACC/REMAP who work with a committed group of research coordinators to enroll patients at three hospitals in Winnipeg both on hospital wards and in the ICU.

ATTACC is funded by Canadian Institutes of Health Research (CIHR) ($3.6 million), LifeArc Foundation ($1.7 million), Peter Munk Cardiac Centre ($250,000) and Thistledown Foundation ($500,000). REMAP is funded by CIHR ($1.1 million). Zarychanski credits Research Manitoba, CancerCare Manitoba, and the Victoria General Hospital Foundation with providing essential start-up fund­ing that was leveraged to secure national and international funding.

Zarychanski’s team was able to quickly pivot to COVID-19 research due to their experience running clinical trials in hospitalized patients. As cases mount, they are working diligently to figure out whether heparin or other drugs will be effective treatments.

“It has been an exhausting experience for our research team–incredible responsibility and with an obvious expectation to finish the trials as soon as humanly possible,” he notes. “In the COVID world, two months feels like two years.”

A new model

While we wait for COVID-19 vaccinations in 2021, researchers are racing to find ways to treat the virus and its ensuing complications. In direct response to the challenges presented by the pandemic, teams were required to create or adopt novel methods to design and run trials.

The ATTACC/REMAP/ACTIV-4 multi-platform trial is helping to put UM and Manitoba on the map in the world of clinical trials. Using innova­tive trial methods designed specifically to meet the needs of a global pandemic, the Manitoba co-led initiative is expected to have an indelible impact in the ways clinical trials are conducted.

“The uniqueness of COVID-19 urgently called for novel methods in design and conduct of clinical trials,” says Zarychanski. “Manitoba has had a significant leadership role developing new trial methods that are expected to change the landscape of clinical trials going forward.”

Zarychanski calls it a “welcome feather in Manitoba’s cap,” for a Manitoba-co-led and sponsored trial to be supported by the U.S. He expects the new methods incorporated into ATTACC/REMAP/ACTIV will inform the design and conduct of international clinical trials in a post-COVID world.

“It’s a compelling model for international collaboration, and I can see already that design elements and methods we’ve created are being translated into other clinical trials in non-COVID disease states,” says Zarychanski. “The experi­ence conducting ATTACC and other COVID-19 trials is serving to increase UM’s research capacity and train the next generation of clinical trialists in Manitoba.”

Hip to Heparin is one of the feature stories in the Winter 2021 issue of ResearchLIFE magazine.

Three clinical trial platforms spanning five continents in over 300 hospitals, have been working together since May 2020 to urgently test whether there is a greater benefit of full doses of heparin (blood thinners) to treat adults hospitalized for non-critical COVID-19 illness compared to the lower dose typically administered to prevent blood clots in hospitalized patients.

Based on the interim results of more than 1300 moderately ill patients admitted to hospital, findings showed that full doses of blood thinners were not only safe, but superior to the doses normally given to prevent blood clots in hospitalized patients. Moderately ill patients are those not in ICU and who did not receive organ support such as mechanical ventilation at trial enrollment. The trial investigators are now working as fast as possible to make the full results of the study available so clinicians can make informed decisions about treating their COVID-19 patients.

These trial results reported today complement the group’s findings announced in December that routine use of full-dose anti-coagulation when started in the ICU in critically ill COVID-19 patients was not beneficial and appeared to be harmful. 

“In a disease with a limited number of effective therapies, our results have the potential  to define a new standard of care for moderately ill hospitalized COVID-19 patients around the world,” said Ryan Zarychanski, MD, M.Sc., associate professor, hematologist and critical care physician at the University of Manitoba and CancerCare Manitoba, Canada, and chair of the Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC) platform and of the therapeutic anticoagulation domain of the Randomized, Embedded, Multi-factorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP).

Early in the pandemic, physicians around the world observed increased rates of blood clots and inflammation among COVID-19 patients which affected multiple organs and led to complications such as lung failure, heart attack and stroke. Whether providing increased doses of blood thinners routinely administered to hospitalized patients would be safe and effective was unknown at that time.

“These results are very exciting and lead us to better understand the impact of applying the right therapies at the right time in the course of this challenging disease,” said Dr. Judith Hochman, chair of Accelerating COVID-19 Therapeutic Interventions and Vaccines-4 (ACTIV-4) platform, Harold Snyder Family Professor & Associate Director of Cardiology, Senior Associate Dean for Clinical Sciences and Co-Director, NYU-HHC Clinical and Translational Science Institute, NYU Grossman School of Medicine.

Knowing the effect of full dose blood thinners in hospitalized patients with non-critical disease was a key outstanding question that has now been answered.  Most COVID-19 patients hospitalized are non-critical and this study will impact their care and outcomes. The multiplatform trial further paves the way for future collaborations on a global scale.

“These are the first multi-platform international clinical trials ever undertaken and given the rapid discovery of Heparin’s positive impact on  patient outcomes during the middle of the deadly COVID-19 pandemic, I don’t think it will be the last time researchers, clinicians and patients join forces across continents to test potential treatments against any number of diseases,” said Patrick Lawler, MD, MPH cardiologist at the University of Toronto and Peter Munk Cardiac Centre at University Health Network, who was co-principal investigator of ATTACC and a member of the international trial steering committee for REMAP-CAP.

“Having cared for so many severely ill Covid-19 patients and witnessed the suffering involved for patients and their loved ones, it is profoundly gratifying that together we have discovered a treatment that can prevent patients from becoming severely ill and improve their recovery,” said critical care physician Ewan Goligher, MD, PhD, and co-chair of the therapeutic anticoagulation domain in REMAP-CAP, and assistant professor of medicine, University of Toronto and scientist, University Health Network

Clinical trials, overseen by independent boards, routinely review data. The positive conclusions drawn from results to date at these trial sites have now led to enrollment being stopped. However, an adaptive approach in response to scientific data enables this study, like others, to conduct safe, rapid testing of additional agents and evolve accordingly.

The trials are supported by multiple international funding organizations including Canadian Institutes of Health Research (CAN), the LifeArc Foundation, the NIH National Heart, Lung & Blood Institute, Translational Breast Cancer Research Consortium and the UPMC Learning While Doing Program  (US), National Institute for Health Research (UK), National Health and Medical Research Council (AUS), Health Research Council of New Zealand,  and the PREPARE and RECOVER consortia (EU).

As is normal for clinical trials, these trials are overseen by independent boards that routinely review the data and are composed of experts in ethics, biostatistics, clinical trials, and blood clotting disorders. Informed by the deliberations of these oversight boards, all of the trial sites have paused enrollment of the most critically ill hospitalized patients with COVID-19. A potential for harm in this sub-group could not be excluded. Increased bleeding is a known complication of full-dose anticoagulation. The trials are working urgently to undertake additional analyses which will be made available as soon as possible.  

At the recommendation of the oversight boards, patients who do not require ICU care at the time of enrollment will continue to be enrolled in the trial. Whether the use of full-dose compared to low-dose blood thinners leads to better outcomes in hospitalized patients with less severe disease remains a very important question.  

COVID-19 is associated with significant inflammation and clinical and pathologic evidence of widespread blood clots. These trials were launched because clinicians have observed that many patients ill with COVID-19, including those who have died from the disease, formed blood clots throughout their bodies, even in their smallest blood vessels. This unusual clotting can cause multiple health complications, including lung failure, heart attack, and stroke.

“In only our most critically ill patients with COVID-19, all of our trial sites have paused enrollment while we further analyze the data. These results question the benefit of giving full dose anticoagulants routinely in COVID-19 patients who are admitted to an ICU,” said Dr. Ryan Zarychanski, associate professor of medicine at the University of Manitoba and CancerCare Manitoba, a hematologist and critical care physician, who led the harmonization of the three trials.

The multiple-platform, randomized controlled trial (mpRCT) represents an unprecedented collaboration between three international partners. The Randomized, Embedded, Multi-factorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) Therapeutic Anticoagulation; Accelerating COVID-19 Therapeutic Interventions and Vaccines-4 (ACTIV-4) Antithrombotics Inpatient; and Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC) are a set of clinical trial platforms spanning five continents with the common goal of testing whether there is a benefit of full doses of blood thinners to treat adults hospitalized for COVID-19 illness on the ward or in the ICU compared to the lower dose used to prevent blood clots in hospitalized patients. To meet the challenge of this pandemic, investigators worldwide joined forces to answer this question as rapidly as possible.

“These results represent an immense collaborative effort involving patients, clinicians, and research staff around the world enabling us to rapidly learn how best to treat Covid-19,” says Dr. Ewan Goligher, assistant professor of medicine, University of Toronto and scientist, Toronto General Hospital Research Institute, University Health Network, and critical care physician. “The strength of the multiplatform clinical trial design enables us to pause in one subset and continue parts of the study.”

The trials are supported by multiple international funding organizations including Canadian Institutes of Health Research (CAN), National Institutes of Health Research (UK), National Health and Medical Research Council (AUS) and the National Institutes of Health (US) and the PREPARE and RECOVER consortia (EU).

In Canada, the collaboration was funded by Canadian Institutes of Health Research, LifeArc Foundation, Research Manitoba, Thistledown Foundation, Province of Ontario and Peter Munk Cardiac Centre at UHN.

The Honourable Patty Hajdu, Canada’s Minister of Health, announced the funding from the Government of Canada, through the Canadian Institutes of Health Research (CIHR), along with provincial partners, that invests more than $109 million over one year in COVID-19 research.

“I congratulate our successful investigators and their partners and collaborators for their essential research to address this global health emergency,” said Dr. Digvir Jayas, Vice-President (Research and International) and Distinguished Professor at UM.

The six UM researchers who are having their projects supported through CIHR and Research Manitoba include five located at the Max Rady College of Medicine and one at the Faculty of Arts.

Faculty of Arts:

Lori Wilkinson (Sociology and Criminology), CIHR – $671,332

Lori Wilkinson

The COVID-19 virus preys on people in vulnerable situations such as overcrowded housing and work stations, these conditions are frequent among racialized persons, Indigenous persons and newcomers, Wilkinson’s project will seeks answers to questions impacting populations of Indigenous, racialized persons and newcomers, in Canada, the U.S. and Mexico. The project will seek answers to two central questions: How have COVID-19 related government imposed regulations differentially influenced the mental health and well-being of Indigenous peoples, racialized persons and immigrants? And, to what extent have socioeconomic inequalities faced by Indigenous peoples, racialized persons and immigrants influenced their experience of COVID-19 and its related social and economic restrictions?

Max Rady College of Medicine:

Meghan Azad (Pediatrics & Child Health/Children’s Hospital Research Institute of Manitoba), Canada Research Chair in Developmental Origins of Chronic Disease, CIHR awarded $1,639,795; Research Manitoba awarded $100,000

Meghan Azad.

Social distancing policies and school and business closures have helped slow the spread of COVID-19, but we don’t know how they will affect mental health and wellbeing (especially in children) in the long term. We also don’t know why some people infected with the novel coronavirus get very sick and others do not, and we don’t know the true rate of infection in the population. These are urgent questions that must be answered quickly to control outbreaks and minimize the unintended consequences of pandemic management policies.  Azad and her team will study the direct effects of coronavirus infection and the indirect effects of the COVID-19 pandemic in the existing CHILD Cohort Study.

Kevin Coombs (Medical Microbiology & Infectious Diseases/Children’s Hospital Research Institute of Manitoba), CIHR awarded $790,162

Kevin Coombs

All strategies of rapidly developing tools to mitigate this catastrophic SARS-CoV-2 pandemic are fundamentally dependent on identifying and controlling those proteins that execute the cellular mechanisms critical for the virus to infect and replicate in host cells. Coombs will lead a multi-institutional consortium using a powerful novel tool, called SOMAscan, and next-generation sequencing, to rapidly determine how COVID-19 (SARS-CoV-2 coronavirus) – and a variety of other coronaviruses – affect large numbers of genes and proteins in different human lung cells, the normal target of the COVID-19 virus.

Josée Lavoie (Community Health Sciences/Indigenous Institute of Health and Healing Ongomiizwin – Research), Leona Star and Wanda Phillips-Beck, First Nations Health and Social Secretariat of Manitoba, CIHR awarded $475,836

Josée Lavoie

The COVID-19 pandemic highlighted the importance of modeling in estimating the course of the infection over time, the potential impact of public health measures and the resources required to meet response need. Lavoie—working in full partnership with the First Nations Health and Social Secretariat of Manitoba (FNHSSM)—a seasoned team of First Nations organization-based and university-based researchers with a long history of collaborating, will develop a FNHSSM-based agile platform, for modeling community pandemics. Models will be developed with data from community profiles, evidence of transmission and severity derived from the literature and approaches co-created through knowledge exchange.  This unique project will strengthen an existing platform and be made scalable to other Indigenous contexts.

Nathan Nickel (Community Health Sciences/Manitoba Centre for Health Policy/Children’s Hospital Research Institute of Manitoba), Leona Star, Wanda Phillips-Beck, Francis Chartrand, Julianne Sanguins, Rachel Dutton, Wayne Clark, CIHR – $317,917

Nathan Nickel

Some groups of Canadians are likely to be harder hit by the COVID-19 pandemic than others. First Nations, Métis and Inuit Canadians are examples of these. These groups have high rates of chronic illnesses (like heart disease and lung disease) that put them at high risk for poor COVID-19 outcomes. Nickel is undertaking this project in partnership with the First Nations Health and Social Secretariat, the Manitoba Metis Federation and the Manitoba Inuit Association. It will provide data on who is being tested for COVID-19, using the province of Manitoba as a sample for the rest of Canada. This information can then be used to direct and scale-up the public health response to COVID-19 where it is most needed.

Ryan Zarychanski (Internal Medicine/Research Institute of Oncology and Hematology), CIHR – $3,573,336

Ryan Zarychanski

COVID-19 is associated with inflammation and an unusually high risk of blood clots. Small studies have suggested that anticoagulant (blood thinning) medications reduce inflammation and prevent blood clots from forming and may improve the health and survival of hospitalized patients with COVID-19. The goal of this randomized trial is to establish whether anticoagulants called heparins can improve outcomes in hospitalized patients with COVID-19. This international trial will enroll patients from Canada, the U.S., Brazil and Mexico. Zarychanski is also a co-principal investigator with Dr. Alexis Turgeon (Université Laval) on another CIHR COVID-19 Rapid Response grant ($2.1 million) to further investigate heparin anticoagulation in patients who are critically ill.