University Health Network

Sunnybrook Health Sciences Centre

Subheadline

"These results are the start of an important shift in understanding the way in which diversity contributes to better quality care around the time of surgery"

Greater sex diversity in hospital anaesthesia-surgery teams is associated with better post-operative outcomes for patients, according to a study from ICES, Sunnybrook Research Institute and the UUֱ��.

The study, published in the British Journal of Surgery, found that teams with more than 35 per cent female anesthesiologists and surgeons were associated with a three per cent reduction in odds of post-operative complications in the three months following surgery.

This is one of the first studies to focus on sex diversity of operating room teams, building on past work that has compared the impact of individual surgeon and anesthesiologist characteristics on patient outcomes.

“We wanted to challenge the binary approach of comparing female and male clinicians and rather highlight the importance of diversity as a team asset or bonus in enhancing quality care,” says lead author Julie Hallet, a scientist with ICES and Sunnybrook Research Institute, and associate professor of surgery at UUֱ��’s Temerty Faculty of Medicine.

The study includes population-based, health-care data on 709,899 adult patients undergoing major in-patient surgeries in Ontario between 2009 and 2019.

Sex diversity of surgical teams was defined as the percentage of female anesthesiologists and surgeons among all anesthesiologists and surgeons working in the hospital each year. The primary outcome was 90-day major morbidity, which the researchers analyzed with a standardized classification scale to identify severe post-surgical complications.

The findings showed that reaching a critical mass of more than 35 per cent female anesthesiologists and surgeons was linked to lower odds of severe complications.

The association between greater sex diversity and reduced post-surgical complications was even greater for patients treated by female anesthesiologists and female surgeons – which aligns with previous studies comparing outcomes of male to female surgeons.

“These results are the start of an important shift in understanding the way in which diversity contributes to better quality care around the time of surgery,” says Hallet. “Ensuring a critical mass of female anesthesiologists and surgeons in operative teams is crucial to performance. Below a critical mass, female clinicians may withhold their perspectives, such that the benefits of diversity can only be achieved once minimum representation is reached.”

One limitation of the study is that the data did not include gender as a social construct. It is possible that gender roles, behaviours and attitudes would have influenced the strength of the association.

The study’s authors noted further research is also needed to explore diversity based on other sociodemographic variables, including but not limited to race and ethnicity.

Nevertheless, this study is the first to show a robust positive association between team sex diversity, patient outcomes and quality care.

“We hope that these results will encourage hospitals to intentionally foster sex diversity in operating room teams to reduce poor health outcomes, which, in turn, can improve patient satisfaction and promote sustainability of health systems,” says Gianni Lorello, staff anesthesiologist at Toronto Western Hospital, University Health Network and an associate professor in Temerty Medicine’s department of anesthesiology and pain medicine.

“Ensuring sex diversity in operative teams will require intentional effort for recruitment and retainment policies for female physicians, structural interventions such as minimum representation on teams, and monitoring and reporting of teams’ composition to build institutional accountability in existing systems.”

The research was supported by the Sunnybrook Alternate Funding Plan Innovation Fund.

Researchers uncover DNA repair mechanism that could yield treatments for cancer, premature aging

Christopher.Sorensen — Wed, 08 May 2024 14:03:08 +0000

Researchers uncover DNA repair mechanism that could yield treatments for cancer, premature aging

Christopher.Sorensen Wed, 05/08/2024 - 10:03

Cutline

From left to right: researchers Mia Stanić, Razqallah Hakem, Mitra Shokrollahi, Karim Mekhail and Anisha Hundal (photo by Erin Howe)

Erin Howe

Topic

Princess Margaret Cancer Centre

Laboratory Medicine and Pathobiology

Resarch & Innovation

Cancer

Subheadline

“It’s exciting to think about where these findings will lead us next”

Researchers at the UUֱ�� and partner hospitals have discovered a DNA repair mechanism that advances understanding of how human cells stay healthy – a finding that could lead to new treatments for cancer and premature aging.

The study, published in the journal Nature Structural and Molecular Biology, also sheds light on the mechanism of action of some existing chemotherapy drugs.

“We think this research solves the mystery of how DNA double-strand breaks and the nuclear envelope connect for repair in human cells,” said Karim Mekhail, co-principal investigator on the study and a professor of laboratory medicine and pathobiology in UUֱ��’s Temerty Faculty of Medicine.

“It also makes many previously published discoveries in other organisms applicable in the context of human DNA repair, which should help science move even faster.”

DNA double-strand breaks arise when cells are exposed to radiation and chemicals, and through internal processes such as DNA replication. They are one of the most serious types of DNA damage because they can stall cell growth or put it in overdrive, promoting aging and cancer.

The new discovery, made in human cells and in collaboration with Razqallah Hakem – a senior scientist at UHN’s Princess Margaret Cancer Centre, University Health Network, and a professor in Temerty Medicine’s department of medical biophysics and department of laboratory medicine and pathobiology – extends prior research on DNA damage in yeast by Mekhail and other scientists.

In 2015, Mekhail and collaborators showed how motor proteins deep inside the nucleus of yeast cells transport double-strand breaks to “DNA hospital-like” protein complexes embedded in the nuclear envelope at the edge of the nucleus.

Other studies uncovered related mechanisms during DNA repair in flies and other organisms. However, scientists exploring similar mechanisms in human and other mammalian cells reported little to no DNA mobility for most breaks.

“We knew that nuclear envelope proteins were important for DNA repair across most of these organisms, so we wondered how to explain the limited mobility of damaged DNA in mammalian cells,” Mekhail says.

The answer is both surprising and elegant.

When DNA inside the nucleus of a human cell is damaged, a specific network of microtubule filaments forms in the cytoplasm around the nucleus and pushes on the nuclear envelope. This prompts the formation of tiny tubes, or tubules, which reach into the nucleus and catch most double-strand breaks.

“It’s like fingers pushing on a balloon,” says Mekhail. “When you squeeze a balloon, your fingers form tunnels in its structure, which forces some parts of the balloon’s exterior inside itself.”

Further research by the study authors detailed several aspects of this process. Enzymes called DNA damage response kinases and tubulin acetyltransferase are the master regulators of the process, and promote the formation of the tubules.

Enzymes deposit a chemical mark on a specific part of the microtubule filaments, which causes them to recruit tiny motor proteins and push on the nuclear envelope. Consequently, the repair-promoting protein complexes push the envelope deep into the nucleus, creating bridges to the DNA breaks.

“This ensures that the nucleus undergoes a form of reversible metamorphosis, allowing the envelope to temporarily infiltrate DNA throughout the nucleus, capturing and reconnecting broken DNA,” says Mekhail.

The findings have significant implications for some cancer treatments.

Normal cells use the nuclear envelope tubules to repair DNA, but cancer cells appear to need them more. To explore the mechanism's potential impact, the team analyzed data representing over 8,500 patients with various cancers. The need was visible in several cancers, including triple-negative breast cancer, which is highly aggressive.

“There is a huge effort to identify new therapeutic avenues for cancer patients, and this discovery is a big step forward,” says Hakem.

“Until now, scientists were unclear as to the relative impact of the nuclear envelope in the repair of damaged DNA in human cells. Our collaboration revealed that targeting factors that modulate the nuclear envelope for damaged DNA repair effectively restrains breast cancer development,” Hakem says.

In the aggressive triple-negative breast cancer, there are elevated levels of the tubules – likely because they have more DNA damage than normal cells. When the researchers knocked out the genes needed to control the tubules, cancer cells were less able to form tumours.

One medication used to treat triple-negative breast cancer is a class of drugs called PARP inhibitors. PARP is an enzyme that binds to damaged DNA and helps repair it. PARP inhibitors block the enzyme from performing repair, preventing the ends of a DNA double-strand break in cancer cells from reconnecting to one another.

The cancer cells end up joining two broken ends that are not part of the same pair. As more mismatched pairs are created, the resulting DNA structures become impossible for cells to copy and divide.

“Our study shows that the drug’s ability to trigger these mismatches relies on the tubules. When fewer tubules are present, cancer cells are more resistant to PARP inhibitors,” says Hakem.

Mekhail says the work underscores the importance of cross-disciplinary collaboration.

“The brain power behind every project is crucial. Every team member counts. Also, every right collaborator added to the research project is akin to earning another doctorate in a new specialty – it’s powerful,” he says.

Mekhail notes the discovery is also relevant to premature aging conditions like progeria. The rare genetic condition causes rapid aging within the first two decades of life, commonly leading to early death.

Progeria is linked to a gene coding for lamin A. Mutations in this gene reduce the rigidity of the nuclear envelope. The team found that expression of mutant lamin A is sufficient to induce the tubules, which DNA damaging agents further boosted. The team thinks that even weak pressure on the nuclear envelope spurs the creation of tubules in premature aging cells.

The findings suggest that in progeria, DNA repair may be compromised by the presence of too many or poorly regulated tubules. The study results also have implications for many other clinical conditions, Mekhail says.

“It’s exciting to think about where these findings will lead us next,” says Mekhail. “We have excellent colleagues and incredible trainees here at Temerty Medicine and in our partner hospitals. We’re already working toward following this discovery and using our work to create novel therapeutics.”

The research was supported by the Canadian Institutes of Health Research, Royal Society of Canada, UUֱ�� and Princess Margaret Hospital.

UUֱ��, hospitals launch pilot program to boost commercialization of medical innovations

rahul.kalvapalle — Wed, 24 Apr 2024 14:19:19 +0000

UUֱ��, hospitals launch pilot program to boost commercialization of medical innovations

rahul.kalvapalle Wed, 04/24/2024 - 10:19

Cutline

(photo by Daria Perevezentsev)

Rahul Kalvapalle

Topic

Institutional Strategic Initiatives

Acceleration Consortium

Sunnybrook Health Sciences Centre

Artificial Intelligence

Department of Chemistry

Department of Computer Science

Entrepreneurship

Faculty of Art & Science

Hospital for Sick Children

Leslie Dan Faculty of Pharmacy

Startups

The UUֱ�� is collaborating with the University Health Network, the Hospital for Sick Children and Sunnybrook Research Institute on a new program that aims to leverage the expertise of entrepreneurs and business leaders to advance commercialization of emerging medical technologies and regenerative medicine research.

Funded by the Government of Ontario, the Entrepreneur-In-Residence program will support projects that display high potential for clinical impact and spin-off company formation, spanning areas ranging from regenerative therapies and medical devices to AI-powered clinical tools and apps for patient care.

The one-year pilot program is being launched with the help of a $300,000 grant from Intellectual Property Ontario (IPON), a provincial agency that was established in 2022 to provide IP resources and supports to researchers and businesses.

“The Entrepreneur-in-Residence program will help take medical innovations developed in academic and hospital environments and translate them into the commercial arena, generating economic opportunity for the region and expanding clinical impact globally,” said Leah Cowen, UUֱ��’s vice-president, research and innovation, and strategic initiatives.

“The UUֱ�� is grateful to IPON for its support of this initiative, which stands to strengthen existing networks of knowledge exchange and collaboration between the university and its partner hospitals.”

Jill Dunlop, left,Ontario’s minister of colleges and universities, said post-secondary institutions are critical incubators of innovation and commercialization (photo courtesy of IPON)

The program will see Entrepreneurs-in-Residence – individuals with a track record of launching science-based ventures and shepherding projects from proof-of-concept to incubation, acceleration and seed funding – liaise with UUֱ��’s Innovations & Partnerships Office and IPON to generate and protect IP. It is designed to add capacity and scope to UUֱ��’s thriving entrepreneurship and commercialization ecosystem, including existing Entrepreneur-in-Residence initiatives such as those offered by the Temerty Faculty of Medicine and Medicine By Design, an institutional strategic initiative (ISI).

“In today’s global knowledge-based economy, Ontario’s post-secondary institutions are critical – not just as centres of learning, but as incubators for innovation and commercialization,” said Jill Dunlop, minister of colleges and universities, in a recent announcement of new IPON-funded initiatives.

“Through the province’s support of IPON, our government is ensuring the social and economic benefits of publicly funded research stay in our province, so that Ontarians and the Ontario economy benefit from these new discoveries and innovations.”

Dunlop also spoke at an April 8 event with Christine Allen, a professor in UUֱ��’s Leslie Dan Faculty of Pharmacy who has an extensive track record of translating and commercializing lab discoveries.

Christine Allen, far right, is a professor in the Leslie Dan Faculty of Pharmacy and the founder and CEO of Intrepid Labs (photo courtesy of IPON)

At the event, Allen highlighted the growth of her startup, Intrepid Labs Inc., which she co-founded with Alán Aspuru-Guzik, a professor in the departments of chemistry and computer science in UUֱ��’s Faculty of Arts & Science and director of the Acceleration Consortium. The company marries Allen’s prowess in drug formulation and development with Aspuru-Guzik’s expertise in AI and advanced computing in order to accelerate the development of next-generation medicines. In the fall, the company closed a pre-seed round of US$4 million.

“The availability of top-notch talent in AI and life sciences made Toronto a great place to launch our company,” says Allen, who is Intrepid’s CEO, noting all four of the startup’s co-founders are from UUֱ��.

She added that UUֱ�� is a powerhouse for entrepreneurship and intellectual property, ranked second in North America for university-based startups, and that companies with founders or co-founders from UUֱ�� make up a significant percentage of some of the fastest-growing companies in Ontario.

“This is the beauty of being at the UUֱ�� and having the MaRS Discovery District across the street and all the hospitals around us. It’s such a rich environment,” she says.

“We can do this in Toronto.”

Allen stressed that a thriving lab-to-market ecosystem is critical to inspire the next generation of entrepreneurs.

“Students are increasingly seeking out roles in the private sector,” she says. “For them to see other students and faculty members [found startups] helps them realize that it’s possible for them to start companies, too.”

COVID-19 virus disrupts protein production, study finds

Christopher.Sorensen — Tue, 23 Apr 2024 20:58:38 +0000

COVID-19 virus disrupts protein production, study finds

Christopher.Sorensen Tue, 04/23/2024 - 16:58

Cutline

This transmission electron microscope image shows SARS-CoV-2, the virus that causes COVID-19, isolated from a patient in the U.S. (photo by NIAID)

Jenni Bozec

Topic

COVID-19

Laboratory Medicine and Pathobiology

Subheadline

Post-doctoral researcher Talya Yerlici calls SARS-CoV-2 "a clever saboteur inside our cells, making sure its own needs are met while disrupting our cells’ ability to defend themselves"

Despite huge advances in our understanding of COVID-19 over the past four years, the disease is still very much among us – and there remains a lot to learn.

One thing we do know: Following infection, it’s critical that our cells make new proteins to defend against the virus.

(photo supplied)

But Talya Yerlici, a post-doctoral researcher at the UUֱ��’s Temerty Faculty of Medicine, recently showed how SARS-CoV-2 disrupts the manufacture of proteins.

She is the first author of a paper detailing the process that was published recently in the journal Cell Reports.

Writer Jenni Bozec recently spoke with Yerlici – who is based in the lab of Professor Karim Mekhail in the department of laboratory medicine and pathobiology – about the findings.

What have you discovered about how COVID-19 uses proteins?

One way SARS-CoV-2 makes us sick is by using a strategy called “host shutoff.” This means that while the virus makes copies of itself, it also slows the production of vital components within our cells. As a result, our bodies take longer to respond to the infection.

When SARS-CoV-2 enters our cells, it disrupts the process of making proteins, which are essential for our cells to work correctly. A particular SARS-CoV-2 protein called Nsp1 has a crucial role in this process. It stops ribosomes, the machinery that makes proteins, from doing their job effectively. The virus is like a clever saboteur inside our cells, making sure its own needs are met while disrupting our cells’ ability to defend themselves.

We found that Nsp1 is good at blocking ribosomes from making new proteins, but also interferes with the production of new ribosomes. In effect, it shuts down the machinery output and the ability to make the machinery itself – a serious double hit.

It does this by blocking the maturation or processing of specialized RNA molecules needed to build ribosomes. This adds a new layer of complexity to our understanding of SARS-CoV-2's interference with the host cell.

How could this discovery impact treatment for those with COVID-19?

Building on our published research, it will be crucial to understand how Nsp1 works to stop different types of human cells, tissues and organs from making proteins when infected with different variants of SARS-CoV-2 and related coronaviruses.

Scientists have been working to find precision medicines that can counteract Nsp1 and help fight against the continually evolving SARS-CoV-2 virus. These drugs aim to help infected cells keep producing proteins and build a robust immune response when dealing with infection. Ongoing research on such drugs should now benefit from testing whether they can block Nsp1 from interfering with both the production and function of ribosomes, and this should help find more effective precision medicines.

What drew you to this line of research?

This project started because of circumstances during the COVID lockdown. We wanted to help in the fight against the pandemic. However, since I couldn't physically work in the lab, we took the opportunity to analyze next-generation sequencing datasets computationally from home.

Looking at published RNA-sequencing datasets, we realized that cells infected with SARS-CoV-2, compared to uninfected cells, may have difficulty processing the RNA molecules needed to build ribosomes. Through this analysis, together with Dr. Mekhail, we developed hypotheses and designed the project.

I had the privilege of collaborating closely with the talented members of the Mekhail lab, including Alexander Palazzo’s group from the department of biochemistry at Temerty Medicine and Brian Raught and Razqallah Hakem’s labs at the Princess Margaret Cancer Centre (University Health Network). This work wouldn't have been possible without the collective efforts of our team and collaborators, and I’m grateful for their contributions. My responsibilities included conducting numerous hands-on experiments and bioinformatics analyses, analyzing the results and preparing the paper for peer review and publication.

What were the most challenging and rewarding aspects of this project?

The most challenging part was conducting research during a global pandemic, which presented many logistical hurdles – from disrupted lab routines to limitations on collecting and using samples infected with SARS-CoV-2.

On the other hand, the opportunity to contribute to our understanding of SARS-CoV-2 viral mechanisms and shed light on potential therapeutic targets was incredibly fulfilling. Seeing our research culminate in a published paper and knowing it could inform future strategies for combating coronaviruses is deeply gratifying.

What are your longer-term goals as a scientist?

As an independent investigator in my future lab, I want to study how the complex processes of making ribosomes affect the body's natural defense against viruses. It's an area I find compelling and presents ample opportunities for further exploration. One approach I’m particularly interested in is integrating RNA-sequencing with genetic CRISPR and small-molecule chemical screens, targeting distinct stages of ribosome biogenesis across diverse infection or infection-mimicking conditions. Such integrated approaches hold promise for uncovering novel mechanisms underlying the regulation of antiviral responses and should help us find innovative and impactful ways to fight viral infections.

This research was supported by the Canadian Institutes of Health Research.

Heart-on-a-chip model used to glean insights into COVID-19-induced heart inflammation

Christopher.Sorensen — Mon, 08 Apr 2024 19:06:23 +0000

Heart-on-a-chip model used to glean insights into COVID-19-induced heart inflammation

Christopher.Sorensen Mon, 04/08/2024 - 15:06

Cutline

Researchers worked in the Toronto High Containment Facility at UUֱ�� to examine the effects of COVID-19 on heart inflammation (photo by Lisa Lightbourn)

Betty Zou

Topic

Institute of Biomedical Engineering

Faculty of Applied Science & Engineering

Unity Health

Alumni

Leslie Dan Faculty of Pharmacy

Subheadline

Researcher dedicates study to her late grandmother, who died from COVID-19-induced heart failure

Researchers at the UUֱ�� and its partner hospitals have created a unique heart-on-a-chip model that is helping untangle the causes of COVID-19-induced heart inflammation and uncover strategies to reduce its impact.

While COVID-19 is primarily a respiratory infection, clinicians and researchers are increasingly aware of the virus’s effects on other organs – including the heart. Data from the U.S. Centers for Disease Control and Prevention shows patients hospitalized with COVID-19 between March 2020 and January 2021 had 15 times higher risk for developing myocarditis, or inflammation of the heart muscle, compared to patients without COVID-19.

But the biology behind the association between SARS-CoV-2 infection and heart inflammation had remained unclear – in part because there have not been good models with which to study infection-related heart inflammation.

“Conventionally, people grow heart cells in a 2D setting and then expose it to SARS-CoV-2 to see how the virus damages the heart. But that’s not actually what happens in our body,” says Rick Lu, a PhD graduate from UUֱ��’s Institute for Biomedical Engineering who is currently a postdoctoral researcher at UUֱ��’s Leslie Dan Faculty of Pharmacy.

Lu is the first author of a new study published in Science Advances that describes a miniature 3D heart-on-a-chip model that more accurately captures the impact of SARS-CoV-2 infection and its associated immune response on cardiac dysfunction.

The first-of-its-kind model builds on previous work led by Milica Radisic, Lu’s PhD adviser, a senior scientist at University Health Network and a UUֱ�� professor of biomedical engineering. The approach uses a lab-made network of blood vessels surrounded by heart tissues grown from stem cells to mimic a real human heart with its tangle of vessels going in and out.

From left to right: Researchers Milica Radisic, Rick Lu and Claudia dos Santos (supplied images)

To examine the effects of COVID-19 on heart inflammation, Lu and his colleagues first had to adapt their model to work in the Toronto High Containment Facility, a specialized lab that allows researchers to study high-risk pathogens like SARS-CoV-2 in a safe and secure way.

“This work would simply not be possible without the Toronto High Containment Facility,” says Radisic, who holds the Canada Research Chair in Organ-on-a-Chip Engineering.

In the high containment lab, the researchers added live virus and immune cells to the blood vessels and allowed them to flow through their mini hearts-on-a-chip, replicating the immune response that happens after a SARS-CoV-2 infection. They found that the combination of SARS-CoV-2 and immune cells reduced the heart’s ability to contract and pump. To understand why, the researchers turned to mitochondria, the tiny energy storehouses that power the muscle’s beating movements. They showed that SARS-CoV-2 infection led to loss of mitochondria and a release of mitochondrial DNA from the heart cells into the nutrient broth used to grow the organoids.

Working with Claudia dos Santos, a scientist and critical care doctor at Unity Health Toronto, associate professor of medicine and Pitts Research Chair in Acute Care and Emergency Medicine at UUֱ��’s Temerty Faculty of Medicine, the researchers then asked whether the presence of freely circulating mitochondrial DNA is also seen in patients experiencing COVID-19-induced heart complications.

They analyzed blood samples from patients with and without COVID-19 and found nearly two-and-a-half times higher levels of mitochondrial DNA in patients who were COVID-19-positive. Their findings point to mitochondrial DNA levels as a powerful predictor of a person’s risk of experiencing cardiac problems after SARS-CoV-2 infection.

The team also showed that a new type of cell-based therapy called exosomes – little cargo vessels that bubble off cells – could reduce inflammation and mitochondria loss, as well as improve heart function, after SARS-CoV-2 infection, highlighting their potential to repair COVID-19-associated heart damage.

By integrating blood vessels and immune cells, Lu hopes that the innovative heart-on-a-chip model can help researchers and clinicians understand and identify treatment strategies for other infection-related heart conditions.

“The good thing about our system is that it’s readily adaptable to any kind of infectious disease,” says Lu. “The other benefit is that we don’t have to rely as much on animal models. Since we’re already using human-derived cells, the clinical translatability is much higher.”

As a next step, Radisic’s group plans to use the miniature organs to uncover why males are more likely than females to experience COVID-19-associated heart complications and to examine the cardiac issues commonly seen in people with long COVID-19.

Radisic says the motivation for this work was deeply personal. She dedicated the study to her late grandmother who died from COVID-19-induced heart failure after six weeks in the intensive care unit.

“The feeling of helplessness is rather profound when a loved one is dying,” she says. “As scientists, we can take small steps toward new cures so that other people do not meet the same fate. For me, this work meant overcoming the feeling of helplessness.”

The work was supported by investments from the Canada Foundation for Innovation and the creation of the UUֱ�� COVID-19 biobank and the Precision Medicine in Critical Care (PREDICT) Biobank at Unity Health Toronto – and by the contributions of patients and families that donated biological samples, making significant advances in research possible.

UUֱ�� receives $10 million from Ontario government for modernization of high containment facility

Christopher.Sorensen — Mon, 18 Mar 2024 18:15:01 +0000

UUֱ�� receives $10 million from Ontario government for modernization of high containment facility

Christopher.Sorensen Mon, 03/18/2024 - 14:15

Cutline

(photo by Julia Soudat)

Betty Zou

Topic

Emerging and Pandemic Infections Consortium

Institutional Strategic Initiatives

Sinai Health

Sunnybrook Health Sciences Centre

Hospital for Sick Children

Unity Health

Health

Subheadline

Renewal of the 20-year-old facility, which allows researchers to study high-risk pathogens, will provide increased capacity to develop new vaccines and therapeutics

Canada’s ability to respond rapidly to emerging infectious diseases is taking a step forward with a $9.9-million investment from the Ontario government to support critical research infrastructure updates to the Toronto High Containment Facility (THCF), which houses the largest containment level 3 lab in the province.

The facility, located at the UUֱ��, is specially equipped to allow researchers to study high-risk pathogens, such as SARS-CoV-2, HIV, tuberculosis and mpox, in a safe and secure way.

Research undertaken at the current facility has advanced our understanding of infectious diseases and strengthened our ability to respond to emerging health threats.

“The THCF strengthens Ontario’s position as a prime location for globally leading companies and top talent to discover and commercialize cutting-edge technologies, while improving our preparedness for future health challenges,” says Leah Cowen, UUֱ��’s vice-president, research and innovation, and strategic initiatives. “The updated facility will enhance Canada’s health infrastructure and health security, and ensure that Canadian researchers are trained and ready to respond to emerging infectious diseases.”

The provincial funding builds on a previous $35-million investment from the Canada Foundation for Innovation to support efforts to revitalize and expand the THCF and to transform it into the largest academic high-containment research centre in Canada.

The renewal of the 20-year-old facility will provide increased capacity to use state-of-the-art approaches supporting academic research projects as well as collaborative industry-led efforts to develop new vaccines and therapeutics for Canadians. The new provincial investment will also allow the facility to meet the growing demand from industry and public sector partners while maintaining ongoing research projects and an agile responsiveness to future outbreaks.

“The new THCF will allow our researchers to work on the most urgent infectious disease threats, provide greater opportunities to engage with government agencies and industry partners, and allow us to provide unique training opportunities for the next generation of infectious disease leaders, building a strong foundation for Canada’s response to future outbreaks,” says Scott Gray-Owen, academic director of the THCF and a professor of molecular genetics in UUֱ��’s Temerty Faculty of Medicine.

The provincial support is part of a suite of investments through the Ontario Research Fund and the Early Researcher Awards that also include support for quantum and artificial intelligence projects at UUֱ��. Support has also been extended to advance an infrastructure renewal of the province’s Advanced Research Computing (ARC) systems, including UUֱ��’s Niagara ARC supercomputer, used by researchers across the country.

As the only high containment facility of its kind in the Greater Toronto Area, the THCF is a unique asset to the life sciences ecosystem in the region, which is home to 55 per cent of Canada’s pharmaceutical companies. The modernized facility will be able to support greater engagement with industry partners to advance made-in-Ontario therapeutics such as the experimental drug paridiprubart from Markham-based Edesa Biotech, which is currently being tested in a Phase 3 clinical trial to treat acute respiratory distress syndrome, a common complication from COVID-19 or influenza infections.

In addition to industry partners, the THCF has been used by federal and provincial agencies including the Public Health Agency of Canada, Bank of Canada, Rogers Hixon Ontario Human Milk Bank and Ontario Ministry of Natural Resources and Forestry.

The THCF renewal will also be undertaken in collaboration with UUֱ��’s hospital partners: The Hospital for Sick Children, Sinai Health, Sunnybrook Health Sciences Centre, Unity Health Toronto and University Health Network. Construction of the facility has begun but the university is seeking additional funding to complete the project.

Based at the Temerty Faculty of Medicine, the THCF is the cornerstone of the Emerging and Pandemic Infections Consortium, a UUֱ�� institutional strategic initiative that brings together the university and Toronto Academic Health Science Network (TAHSN) hospital partners to drive innovative approaches to infectious diseases and prepare for future pandemics. It is also a key infrastructure resource for the Canadian Hub for Health Intelligence and Innovation in Infectious Diseases (HI3) which was established through the Canada Biomedical Research Fund. The hub brings together over 90 partners across several sectors to bolster Canada’s biomanufacturing capacity to ensure a fast and co-ordinated response to future pandemics and infectious threats.

The revitalized THCF will also have the capacity to train more than 100 new highly qualified professionals over a five-year period with industry-relevant skills, including manufacturing practices and vaccine and therapeutics development.

At the beginning of the COVID-19 pandemic, the THCF was the first lab in Canada – and one of the first in the world – to isolate the new coronavirus in March 2020. The facility and its highly trained staff played a key role in accelerating research breakthroughs that guided the pandemic response including, for example, methods to allow safe reuse of personal protective equipment in health-care settings and to ensure safe human milk banking for premature infants.

The THCF was also a core element of EPIC’s mpox rapid research response, housing a biobank of samples from patients with mpox which are being used by researchers to better understand the dynamics of viral shedding and other important questions about the disease.

In addition to a larger physical space, the updated facility will include a state-of-the-art high containment insectary to enable research on mosquito-borne viruses like Chikungunya, dengue, Zika and yellow fever. With its modular design and enhanced safety features, the new facility will also be better positioned to respond to emerging pathogens like highly pathogenic avian influenza.

Weeneebayko Area Health Authority works to transform health care with support of UHN

Christopher.Sorensen — Thu, 11 Jan 2024 16:21:57 +0000

Weeneebayko Area Health Authority works to transform health care with support of UHN

Christopher.Sorensen Thu, 01/11/2024 - 11:21

Cutline

The Weeneebayko Area Health Authority operates the Weeneebayko General Hospital in Moose Factory, Ont., the large, multi-winged building in the foreground (photo by Anne Simard)

Augusta Lipscombe

Topic

Institutional Strategic Initiatives

Ted Rogers Centre for Heart Research

Transform HF

Subheadline

Transform HF, a UUֱ�� institutional strategic initiative focused on digital innovation for heart failure care, is also supporting efforts to bring health care closer to home for the region's communities

Gloria Stoney waited five days in October to be medevaced to Toronto from her home in Peawanuck, Ont. – a Cree community near the shore of Hudson Bay – after she began experiencing serious cardiac symptoms.

“I didn’t feel so comfortable, but my family was there to take care of me and make sure I wasn’t alone,” she says.

Upon arriving at Toronto General Hospital, she was admitted immediately for further work-up and was able to return home to Peawanuck while she was monitored remotely. A short time later, she was flown out to Kingston, Ont., for more testing and returned home at the end of November.

Gloria’s experience criss-crossing the province could soon become less common for local residents thanks to efforts by the Weeneebayko Area Health Authority (WAHA) that are being supported by physicians at the Peter Munk Cardiac Centre, University Health Network (UHN).

With limited access to specialized cardiac care in the region, patients such as Gloria Stoney must travel more than 1,300 kilometres south by a combination of boat, train, plane and car (supplied image)

Building on an existing 2017 partnership, WAHA and UHN have signed a five-year memorandum of understanding that would support the cardiovascular needs of James Bay and Hudson Bay communities with a focus on direct care and remote management. That includes building local capacity and making use of remote technologies and other digital tools to bring diagnostics and treatment closer to where patients live.

“Signing the MOU emphasizes WAHA and UHN’s joint dedication to enhancing cardiac care in the James and Hudson Bay region," says Lynne Innes, WAHA's president and CEO. “Together, we’re working to improve cardiac care delivery, making it more accessible while enhancing quality of life.

“This partnership is a significant example of how health equity can be advanced in Indigenous communities.”

Using both Indigenous and western strategies, WAHA provides health care to six communities throughout the James Bay and Hudson Bay region, including Peawanuck.

Moose River (photo by Anne Simard)

Innes notes there is currently limited access to specialized cardiac care in the region, requiring patients such as Gloria to use a combination of boat, train, plane and car to travel more than 1,300 kilometres to the south.

“Leaving home for medical care is tough,” she says. “It requires the co-ordination of many people and organizations, and for our clients, it can mean a lot of anxiety from having to navigate a different city and hospital, all while missing the comfort of home. It’s a journey of healing mixed with the struggle of being far away from what’s familiar.”

Under the arrangement, co-ordinated clinical care would involve regular in-person visits by UHN staff to WAHA’s six communities and use of the Medly Program – a remote patient monitoring system for heart failure management that already counts more than 30 WAHA community members, including Gloria, as users.

There would also be opportunities for researchers and trainees to engage with WAHA and community members through Transform HF, a UUֱ�� institutional strategic initiative focused on digital innovation for heart failure care that brings together the university and the Ted Rogers Centre for Heart Research – itself a partnership between the UUֱ��, UHN and the Hospital for Sick Children.

Left to right: Samuel Petrie, Stella Kozuszko, Erica Groenewoud, Mena Gewarges, Tanis Ross, Heather Ross, Elaine Innes, Sandra Kioke, Anne Simard and Sahr Wali (supplied photo)

Heather Ross, head of the cardiology division at the Peter Munk Cardiac Centre at UHN and a professor in UUֱ��’s Temerty Faculty of Medicine, says improving access to culturally safe cardiovascular care in WAHA’s communities could drastically improve patient care and outcomes in the region.

“Digital innovation is the key,” says Ross, who is also co-lead of Transform HF. “It can provide access to health-care services not historically offered in the region and that require clients to travel out of community.”

A recent community-based study in Moosonee, Ont., found that community members are receptive to digital health tools, though they must be designed in a way that reflects their values and integrates western and Indigenous approaches.

Gloria, for one, says digital tools such as Medly have made a difference in her life.

“Medly has been helpful,” she says. “It saves me running to the clinic every time something happens. You get a response right away, and someone reaches out to you when something is up.”

Gloria says she also appreciates that her results are available through the app, so when she needs to receive care outside of her community, there’s no need to re-explain her symptoms and management.

“I’m not the only one in Peawanuck with a heart issue,” Gloria says. “Medly benefits a lot of people here.”

The partners are also initiating a screening program for earlier detection and primary prevention of heart failure.

Additionally, the partnership will support ongoing community-based qualitative and quantitative research with a focus on field testing digital devices, point-of-care testing and other innovations in community and on the land.

WAHA and UHN will also work together to build capacity in the community. Mentorship programs will facilitate exposure to clinical and research environments for the next generation of WAHA-based health-care providers, and opportunities will be created for Toronto cardiology residents and fellows to participate in this collaboration through observerships.

“Working in community, with community, is so important – this MOU supports that,” Ross says. “When you add in the layer of digital health and remote monitoring, I think we can support WAHA in keeping their community members healthy at home.”

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Transform HF

With heart-on-a-chip, researchers study genetic mutation underlying cardiac muscle disease

Christopher.Sorensen — Tue, 09 Jan 2024 16:44:17 +0000

With heart-on-a-chip, researchers study genetic mutation underlying cardiac muscle disease

Christopher.Sorensen Tue, 01/09/2024 - 11:44

Cutline

Professor Milica Radisic and UUֱ�� alumna Marianne Wauchop developed a heart-on-a-chip device to study the effects of a genetic mutation that causes dilated cardiomyopathy (supplied images)

Anika Hazra

Topic

Institute of Biomedical Engineering

Donnelly Centre for Cellular & Biomolecular Research

Faculty of Applied Science & Engineering

Subheadline

Device was used to observe the effects of a sodium channel mutation that disrupts regular electrical activity in the heart

Researchers at the UUֱ�� and its partner hospitals have led the development of a heart-on-a-chip device to study the effects of a genetic mutation that causes dilated cardiomyopathy, a heart muscle disease that impairs blood flow throughout the body.

While it’s been difficult to study cardiac muscle cells due to incomplete tissue maturation in the lab, the UUֱ��-led team was able to use the device to mature stem cells into adult cardiac tissue to observe the effects of a sodium channel mutation that disrupts regular electrical activity in the heart.

“Thanks to our heart-on-a-chip, we were able to overcome the challenges associated with the developmental regulation of the sodium channel mutation,” said Marianne Wauchop, first author of the study and former PhD student in the department of physiology in the Temerty Faculty of Medicine and the department of chemical engineering and applied chemistry in the Faculty of Applied Science & Engineering.

“Using the same device, we were also able to determine the effects of the mutation on cardiac function.”

The journal Biomaterials recently published the findings.

The results could help advance personalized treatment for heart diseases such as dilated cardiomyopathy, a heart condition in which the chambers of the heart lose their ability to contract, through a mutation-targeted approach – even in cases where the mutation is not often linked to the disease or associated symptoms. If left untreated, the condition can result in arrhythmia – and eventually heart failure.

“Currently, patients with dilated cardiomyopathy caused by sodium channel mutations are treated for heart failure, such as with beta blockers and diuretics,” said Milica Radisic, a co-principal investigator on the study and professor at UUֱ��’s Donnelly Centre for Cellular and Biomolecular Research and Institute of Biomedical Engineering. “Responses to these treatment methods are varied because they don’t target the specific mutations responsible for dilated cardiomyopathy.”

The researchers found the mutation disrupts interactions between sodium channels and structural proteins that are critical for cardiac muscle cells, leading to tissue dilation and impaired contractile performance.

The cells that carry the mutation were provided for the study by a patient of Kumaraswamy Nanthakumar, senior scientist in the Toronto General Hospital Research Institute at University Health Network and professor at UUֱ��’s Institute of Medical Science in the Temerty Faculty of Medicine.

The patient went into cardiac arrest while giving birth and has a family history of arrythmia, an irregular heartbeat. Nanthakumar sequenced the patient’s genome to identify the particular sodium channel mutation.

“We were faced with the challenge of culturing stem cells that express the mutation in question, as this only occurs following maturation of the cells,” says Wauchop. “To address this issue, we developed a heart-on-a-chip device, also called a biowire, to mature the heart tissues cultured from stem cells.”

The research team created biowires with either tissues taken directly from Nanthakumar’s patient or tissues in which the mutation was corrected with CRISPR, a gene-editing tool.

While it typically takes a few years for patients to start experiencing symptoms of dilated cardiomyopathy after heart cells carrying the sodium channel mutation mature to their adult form, the biowires allowed the team to study the impacts of the mutation on cardiac tissue after only eight weeks.

Throughout this period, the researchers stimulated maturation of the stem cells through electrical current.

Dilated cardiomyopathy and other heart diseases can be caused by more than one type of mutation, Wauchop notes. But, she adds, “We can give patients a fighting chance by first making the connection between the mutation and the disease, and then developing targeted treatments for that specific mutation.”

This research was supported by the Canadian Institutes of Health Research (CIHR), the Peter Munk Cardiac Centre Innovation Committee and the National Institutes of Health (NIH).

UUֱ�� community members recognized with Order of Canada

rahul.kalvapalle — Fri, 05 Jan 2024 21:23:33 +0000

UUֱ�� community members recognized with Order of Canada

rahul.kalvapalle Fri, 01/05/2024 - 16:23

Cutline

(photo by Sgt Johanie Maheu/OSGG-BSGG)

Rahul Kalvapalle

Topic

Centre for Addiction and Mental Health

UTogether

Alumni

Computer Science

Faculty of Arts & Science

Faculty of Music

Order of Canada