Insulin 100

Princess Margaret Cancer Centre

Sunnybrook Health Sciences

University Health Network

Toronto General Hospital

Resarch & Innovation

Medicine by Design

Stem Cell

In a person with type 1 diabetes, the body mistakenly attacks pancreatic cells that produce insulin, a hormone responsible for regulating blood sugar.

Without insulin, serious and eventually fatal symptoms will occur. Yet, imagine if, instead of needing daily insulin injections, people with diabetes could have insulin-producing cells placed back into the body, fixing the problem at its source. This is the vision of a Medicine by Design-funded research team.

The approach is not without its challenges.

“Scientists are able to generate pancreatic cells from stem cells in the lab, and they can be transplanted to someone who has lost pancreatic function, but they’ll be reattacked by the immune system,” says Juan-Carlos Zúñiga-Pflücker, senior scientist at Sunnybrook Research Institute and professor of immunology in the Temerty Faculty of Medicine. “What our work is meant to do is enable those transplants to be broadly acceptable so anyone can benefit from transplanted therapies. But the barrier of the immune system is a difficult thing to overcome, and even more so in the context of autoimmunity.”

The cells are attacked because the immune system recognizes them as harmful invaders instead of helpful therapies. It is a complex problem that demands a complex strategy – and that strategy is an emerging area of research called immunoengineering, which uses bioengineering techniques to manipulate the immune system.

The only way to currently suppress the immune system is through drug treatments, but they’re not selective; they suppress the whole immune system and leave people vulnerable to infection and illness.

The team’s strategy aims to be more precise. They want to finely tune the immune system to maintain a healthy system while not rejecting a therapeutic transplant.

Zúñiga-Pflücker says a collaborative effort is important in solving this major challenge to regenerative medicine. “We can optimize cell types and engineer effective tissues in our separate labs. But if we don’t come together to create better tools to engineer the immune system, these therapies will not be usable. It’s something very fundamental.”

The team is one of 12 sharing nearly $21 million in funding from Medicine by Design over three years. Funded by a $114-million grant from the Canada First Research Excellence Fund, Medicine by Design is a strategic research initiative that is working at the convergence of engineering, medicine and science to catalyze transformative discoveries in regenerative medicine and accelerate them toward clinical impact.

Though the research could be applied broadly across regenerative medicine therapies, type 1 diabetes makes an ideal test case, says Zúñiga-Pflücker, who is also chair of the department of immunology.

“Not only is diabetes an autoimmune disease, where the diabetic’s own immune system attacks and kills insulin producing cells, but attempts to replace the lost cells with transplanted cells are also challenged by other impacts of the disease, as well as the presence of auto-reactive immune cells,” he says. “This makes it a powerful test case for our research since we can test the transplants under multiple immune stresses.”

Zúñiga-Pflücker leads the project, which brings the work of six different labs together.

Two labs, led by the Temerty Faculty of Medicine’s Maria Cristina Nostro, a senior scientist at the University Health Network’s (UHN) McEwen Stem Cell Institute; and Sara Nunes Vasconcelos, a scientist at UHN’s Toronto General Hospital Research Institute, are using stem cells to generate tissues containing insulin-secreting cells for transplants.

Zúñiga-Pflücker says that this arm of the project is well ahead of schedule. “The Nostro and Vasconcelos labs are defining the right conditions that are necessary for generating insulin-producing cells, which are called islet cells. They’re creating newer and more effective ways to make these tissues.”

Nostro and Vasconcelos are also associate professors at ��TV in the department of physiology and Institute of Biomedical Engineering, respectively.

The tissues created in their labs will be used to test the work of the other four labs involved in the project, which are concerned with engineering the immune reaction. And here, each of these labs is bringing a piece of the puzzle.

Read about research into therapeutic cell “cloaking”

Zúñiga-Pflücker and Naoto Hirano, a senior scientist at Princess Margaret Cancer Centre and a professor of immunology at ��TV, work on producing regulatory T cells (Tregs). These cells can supress immune response and play a role in preventing autoimmune diseases like diabetes.

In earlier Medicine by Design-funded research, Zúñiga-Pflücker and Hirano came up with a method for producing T cells in a defined way. Some of the key breakthroughs developed as part of this research helped lay the foundation for Notch Therapeutics, a company co-founded by Zúñiga-Pflücker, which closed an $85-million (U.S.) Series A financing earlier this year.

Now, in the current research project, the two labs are crafting methods for producing Tregs and investigating how harnessing the power of other types of immune cells to work alongside the Tregs can induce the immune system to tolerate transplanted therapies.

The third investigator is Tracy McGaha, whose lab is looking at the role of macrophages, a type of white blood cell that that typically helps to attack foreign substances but can also play a role in repairing damaged tissues. McGaha is a senior scientist at Princess Margaret Cancer Centre, UHN, and a professor in the department of immunology in the Temerty Faculty of Medicine.

A fourth lab, led by Sarah Crome, is investigating a family of immune cells called innate lymphoid cells (ILCs), which act within tissues to help induce and modulate immune responses.

“We know several immune cell populations we individually study can protect from harmful immune responses and promote immune tolerance,” says Crome, who is a scientist at the Toronto General Hospital Research Institute, UHN, and an assistant professor of immunology at ��TV. “The trouble is when you get into a situation that combines an autoimmune disease with rejection that can occur following islet transplantation, it’s a real challenge shutting down multiple harmful and sustained immune responses.”

Crome says that there are many different types of ILCs, so her work focuses on narrowing down which types of ILCs are best to use along with the Tregs.

Right now, each of the four labs working with immune cells are optimizing their cell types and techniques, and then, Crome says they will bring all their “best players” together.

“We’re really looking at harnessing whole networks of cells, instead of just looking at one cell population at a time. It’s bringing all of our collective expertise together into one project that makes this a powerful approach.”

Zúñiga-Pflücker says Medicine by Design has been instrumental in uniting this team of experts.

“Thanks to Medicine by Design’s support of our immunoenigneering program, we’re able to bring together multiple research sites within the University of Toronto and affiliated research institutes; UHN’s Princess Margaret Cancer Centre, Toronto General Hospital Research Institute and McEwen Stem Cell Institute; and Sunnybrook Research Institute.”

Researchers investigate health effects of fracking in B.C.’s Northeast

rahul.kalvapalle — Thu, 25 Nov 2021 18:04:16 +0000

Researchers investigate health effects of fracking in B.C.’s Northeast

rahul.kalvapalle Thu, 11/25/2021 - 13:04

Cutline

��TV's Élyse Caron-Beaudoin and Marianne Hatzopoulou are working together to shed light on how fracking impacts air quality for B.C. communities and residents' exposure to contaminants (photo by Johnny Guatto)

Rahul Kalvapalle

Topic

Faculty of Applied Science & Engineering

Health

Sustainability

��TV Scarborough

With thousands of wells and counting, the Northeast region of British Columbia is one of Canada’s most important hubs of hydraulic fracturing, or fracking – the process of blasting pressurized liquid at rock formations to fracture them and release the natural gas trapped inside.

Part of the region sits atop the Montney Formation, a massive, football-shaped tract of land that stretches into northwestern Alberta and is believed to contain one of the world’s richest reserves of shale gas.

But in addition to releasing gas, fracking also causes the emission of chemicals that can cause or exacerbate health problems including birth defects, cancers and asthma. And while communities located near fracking areas have raised concerns about the health impacts, there has been a dearth of Canadian studies on the topic – until now.

Élyse Caron-Beaudoin, an assistant professor in environmental health in the department of health and society at the University of Toronto Scarborough, is lead author of the only Canadian studies to have explored the health impacts and exposure to contaminants associated with fracking. The latest study, published in Science of the Total Environment, found high levels of some volatile organic compounds (VOCs) in tap water and indoor air in the homes of pregnant women living in the Peace River Valley in Northeast B.C. The study was designed in partnership with the Treaty 8 Tribal Association, the West Moberly First Nations and the Saulteau First Nations.

“Overall, there are consistent associations with negative health effects,” says Caron-Beaudoin, who co-leads one of the only research groups actively investigating the health impacts of fracking in Canada and previously ran a smaller pilot study that found high levels of trace metals in urine and hair samples of pregnant women in two Northeast B.C. communities.

“What we don’t have a lot of in the literature is exposure assessment – measuring the level of exposure of local communities to chemicals that are potentially emitted or released during unconventional natural gas operations.”

To help fill this gap, Caron-Beaudoin is teaming up with Marianne Hatzopoulou, a professor in the department of civil and mineral engineering in the Faculty of Applied Science & Engineering, to shed light on how fracking impacts air quality and exposure to contaminants.

The project combines Hatzopoulou’s expertise in air quality research – modelling road transportation emissions, assessing urban air quality and evaluating population exposure to air pollutants – with Caron-Beaudoin’s scholarship in environmental health to lay the groundwork for a better understanding of the environmental and health justice implications of fracking.

It’s being supported by a $120,000 grant from XSeed, a funding program that aims to catalyze inter-disciplinary research collaborations involving scholars from the Faculty of Applied Science & Engineering and one of ��TV’s other academic divisions.

Hatzopoulou’s first task is to develop air quality models – computer simulations that estimate the concentration of air pollutants generated by an activity, and the degree of population exposure to these contaminants – for various fracking scenarios.

“In urban environments, we try to quantify how much a car emits while it’s driving one kilometre,” says Hatzopoulou. “In industrial settings, we may try to understand how much is emitted from the stack as a function of the production of a certain material. With gas fracking, we try to understand what is being emitted during the different life stages of gas wells.

The modelling, which involves combining existing measurements, data from regulatory agencies and data from published literature, includes creating an “emissions inventory.” It’s effectively a database containing information on the pollutants generated by different kinds of wells across their various stages of operation.

“What the air quality model does is resolve how air pollutants being emitted in the environment are going to disperse because of wind, meteorology, etc., and how they are going to chemically react with other species that are present in the atmosphere. Eventually, the output includes concentrations of multiple air pollutants that individuals are exposed to,” Hatzopolou says.

“Once exposures from the model are assigned to various individuals, we want to investigate how they relate to measurements conducted in homes and other markers in biological samples.”

This is where data from Caron-Beaudoin’s studies – she measured chemicals in indoor air and tap water, as well as the hair and nails of pregnant women – come into play.

“The urine gives you an indication of short-term exposure and the nails and hair more of a long-term exposure, so we can trace their exposure patterns back in time using those different types of samples,” Caron-Beaudoin says.

By probing the associations between Hatzopoulou’s modelled air pollution data and the chemical and biological samples gathered by Caron-Beaudoin, the researchers hope to develop a better understanding of the links between fracking activity and exposure to toxins.

Caron-Beaudoin’s team have also been working on developing exposure metrics related to well density, proximity and the different stages of well operation. That includes well pad preparation, drilling, fracking and gas production. The association between those metrics and modelled fracking emissions will also be investigated.

Ultimately, the goal is to generate evidence – and a suite of tools – to help estimate exposure to contaminants, an area where little knowledge exists due to the exorbitant cost of carrying out ongoing exposure studies.

“A big challenge of exposure assessment is the logistics and cost – it costs a lot of money to go to remote areas and have air quality sampling and water quality sampling,” Caron-Beaudoin says. “Hopefully our project can provide tools to estimate exposure accurately without having to rely on traditional exposure assessment methods that are costly and difficult to implement.”

Hatzopoulou adds that she hopes their work can be leveraged to inform regulations and engineering decisions that make it possible to curb the detrimental health impacts of fracking. What if well numbers are capped in certain areas? Should exploration be concentrated in certain spaces? How can air pollution be minimized through smart engineering decisions?

“This study will provide health and exposure information, which are lacking when regulatory agencies are currently issuing permits for fracking,” Hatzopoulou says.

A more immediate priority is to empower communities with knowledge about the impact of fracking operations on their health. Such information is critical given that the communities located near Canada’s fracking hotspots are disproportionately rural and Indigenous, and are therefore already disadvantaged by health and economic disparities.

“First and foremost, it’s important to arm communities with data about their exposures, what they’re breathing and the impact of what they’re seeing every day,” Hatzopoulou says.

“That’s the goal,” Caron-Beaudoin adds. “To share the data and results with communities so that they have as much information as possible to help make decisions on the types of industrial development happening on their territory.”

Insulin 100: Parks Canada unveils commemorative bronze plaque at ��TV

rahul.kalvapalle — Fri, 12 Nov 2021 20:15:21 +0000

Insulin 100: Parks Canada unveils commemorative bronze plaque at ��TV

rahul.kalvapalle Fri, 11/12/2021 - 15:15

Cutline

Christine Allen, ��TV’s associate vice-president and vice-provost, strategic initiatives, and Christine Loth-Brown, vice-president, Indigenous Affairs and Cultural Heritage, Parks Canada, unveil the plaque (Photo by Johnny Guatto)

Topic

Myhal Centre for Engineering Innovation & Entrepreneurship

Toronto General Hospital

One hundred years ago this month, scientists at the University of Toronto and its partner hospitals carried out the first studies that demonstrated the ability of insulin to lower blood sugar levels in animals and prevent their death from diabetes.

Three months later, insulin was successfully administered to a person with type 1 diabetes at Toronto General Hospital. His life would become the first of millions around the world to be saved by insulin – one of the landmark medical discoveries of the 20^th century.

On Friday, the historical significance of the discovery was marked by the unveiling of a commemorative bronze plaque at a ceremony hosted by Parks Canada and the Historic Sites and Monuments Board of Canada (HSMBC) at the Myhal Centre for Engineering Innovation & Entrepreneurship on ��TV’s St. George campus.

The event was attended by government dignitaries including Sonia Sidhu, member of parliament for Brampton South. The final location of the plaque, which is inscribed by bilingual text, will be determined at a later date.

“The story of insulin is a brilliant example of the power of collaboration – in this case, how a university, its hospital partners and a pharmaceutical company could work together and change the world,” said Christine Allen, ��TV’s associate vice-president and vice-provost, strategic initiatives.

“On this illustrious foundation, ��TV and its hospital and industry partners built a culture of discovery, innovation and collaboration that has transformed health care and continues to have a ripple effect worldwide.

From left: Patricia Brubaker, Richard Alway, Sonia Sidhu, Christine Allen, Christine Loth-Brown and Lynn Wilson (photo by Johnny Guatto)

The ceremony marked the culmination of Insulin 100, a year-long campaign to mark the centenary of insulin’s discovery and celebrate a legacy of health innovation that continues to be advanced by ��TV and its partner hospitals, research institutes and industry partners.

“The Parks Canada plaque not only serves as a fitting reminder of the critical research discoveries made here at ��TV – it will also inspire future trainees and researchers whose work will be pivotal in the health research discoveries made over the next hundred years,” Allen said.

Patricia Brubaker, a professor in the departments of physiology and medicine at the Temerty Faculty of Medicine and member of the faculty’s Banting & Best Diabetes Centre, described the key areas of diabetes research being investigated by ��TV faculty and students today.

“Our interests cover the spectrum of diabetes research, including not only type 1 diabetes, but also type 2 diabetes, which is now reaching epidemic levels, affecting one in six Canadians, as well as gestational diabetes or diabetes during pregnancy,” said Brubaker, who has been conducting diabetes research for four decades.

“We are studying the causes of diabetes through research into obesity, a major risk factor for type 2 diabetes; we are interrogating new approaches to the treatment of diabetes, including stem cell replacement therapy and new pharmacologic treatments; and our researchers are exploring the fundamental mechanisms that underlie the normal regulation of glucose and fat metabolism and how this is disrupted in diabetes, leading to long-term complications such as kidney and cardiovascular disease.”

Brubaker also reflected on the impact of insulin and diabetes research on her own life. As a person living with type 1 diabetes, she noted she is “one of legions who would not be alive today without the discovery of insulin.”

In addition to saving countless lives, the discovery of insulin helped establish ��TV, its partner hospitals and Toronto more generally as a vanguard of diabetes research and treatment.

In April, some of the latest developments in the field were discussed at the Insulin100 conference, a two-day virtual symposium that drew over 6,000 attendees from around the world.

Also in April, ��TV’s Banting & Best Diabetes Centre and Diabetes Action Canada hosted “100 Years of Insulin – Celebrating its Impact on our Lives,” a public celebration and forum featuring an array of topics of interest to people living with diabetes.

It was at this public celebration that Canada Post unveiled a special stamp to commemorate the discovery of insulin. The stamp, which depicts a vial of insulin resting on an excerpt from Banting’s unpublished memoirs, was unveiled from the Banting House National Historic Site of Canada in London, Ont. – in the very room where Banting first got the idea that eventually led to the discovery of insulin. Brubaker and Scott Heximer, chair of the department of physiology at the Temerty Faculty of Medicine and a principal investigator at the Ted Rogers Centre for Heart Research, worked with Canada Post and Banting House to ensure the stamp’s historical accuracy and help source archival material.

The stamp would be the first of several commemorations to mark the place of insulin in the cultural tapestry of Canada’s heritage.

In May, Historica Canada released a Heritage Minutes segment paying tribute to the discovery. The segment depicts the plight of 13-year-old diabetes patient Leonard Thompson, and the efforts of Banting and Best to formulate and refine the insulin treatment that ultimately saves Thompson’s life. Again, experts from ��TV – including science and medicine librarian Alexandra Carter, archivist Natalya Rattan and medical historian Christopher Rutty – were consulted on the project to ensure historical accuracy.

In July, the Royal Canadian Mint issued its own commemoration in the form of a two-dollar coin depicting a monomer (a building block of the insulin molecule), insulin cells, blood cells, glucose and the scientific instruments used in early formulations of insulin.

The importance of insulin was recognized almost immediately after its initial discovery. In 1923, the Nobel Prize in Physiology or Medicine was awarded to Frederick Banting and James McLeod, who isolated insulin in ��TV’s department of physiology. The prize was shared with physiology and biochemistry student Charles Best and biochemist James Collip.

��TV researchers continue to be recognized for their stellar work in advancing diabetes research.

Brubaker was honoured last year with a Lifetime Achievement Award from Diabetes Canada, a recognition of her longstanding contribution to diabetes research and the Canadian diabetes community. And, earlier this year, Daniel Drucker, professor of medicine in the Temerty Faculty of Medicine and a senior investigator at the Lunenfeld-Tanenbaum Research Institute at Sinai Health, was awarded a Canada Gairdner International Award for research on glucagon-like peptides that has helped revolutionize treatments for type 2 diabetes – an honour he shared with collaborators at Harvard University and the University of Copenhagen.

Getting to net-zero emissions – what role does the health-care sector play?

Christopher.Sorensen — Thu, 04 Nov 2021 15:39:35 +0000

Getting to net-zero emissions – what role does the health-care sector play?

Christopher.Sorensen Thu, 11/04/2021 - 11:39

Cutline

Fiona Miller, director of ��TV's Centre for Sustainable Health Systems, says the global health-care sector, if it were a nation, would be the world's fifth-largest emitter of greenhouse gases (photo by Johnny Guatto)

Topic

Institute of Health Policy Management and Evaluation

Dalla Lana School of Public Health

Sustainability

As the world grapples with the negative health effects posed by climate change, Fiona Miller says the health-care sector must not only treat the resulting medical conditions — but take steps to ensure it's not contributing to them.

“In Canada and in most other countries, the health-care sector accounts for about five per cent of greenhouse gas emissions,” says Miller, professor of health policy at the Institute of Health Policy, Management and Evaluation (IHPME) in the Dalla Lana School of Public Health at the University of Toronto.

“Globally, if health care were a nation, it would be the fifth largest emitter.”

Miller is director of IHPME’s Centre for Sustainable Health Systems and chair in Health Management Strategies.

When she speaks of health care and its impact on environmental degradation, Miller is referring to everything involved in caring for the health of society. That includes massive hospitals that require heating and cooling – and may be generating power from coal – to the overuse of single-use medical items such as hypodermic needles and syringes, as well as the packaging that becomes garbage. It includes individuals driving to see a doctor for an in-person physical that may not be medically necessary – and the use of certain kinds of inhalers and anesthetic gases that are not environmentally-friendly.

“The health-care sector is buying an enormous quantity of products,” Miller says. “They own lots of capital and infrastructure. They are very much part of urban environments. And with everything that goes with that, they have negative environmental impacts.”

The paradox, she says, is the health-care sector is inadvertently helping to create new health problems – linked to pollution and climate change – in its effort to treat others.

“We often don’t recognize that these very significant social institutions are part and parcel of climate change.”

But Miller, who recently received a Connaught Global Challenge Award for her work, notes that there are signs the sector is changing its ways.

“Organizations around the world are waking up to their responsibility to manage sustainability,” she says. “Health care is no different in terms of needing to get its house in order and mitigate the environmental harms it is responsible for. In fact, there is a greater obligation in health care because its mission is health.”

Miller points to the precedent-setting work of the National Health Service in England, which has committed to a net-zero health system for the full scope of its direct and indirect emissions by 2045. She also notes Choosing Wisely Canada (which sprung from a U.S. initiative that launched in 2012) that is encouraging health professionals and patients to take a hard look at identifying unnecessary medical tests, treatments and procedures.

And the push for sustainable health care got a big boost earlier this year when Environment and Climate Change Canada awarded $6 million to launch CASCADES (Creating a Sustainable Canadian Health System in a Climate Crisis).

The project is being led by Miller, who is partnering with Sean Christie and Gillian Ritcey of Dalhousie University, Andrea MacNeill of the University of British Columbia, and Linda Varangu of the Canadian Coalition for Green Health Care.

The mandate of CASCADES, says Miller, is to “build and leverage capacity on the front lines, among management and leadership levels, through continuing professional development, knowledge mobilization and networking, supporting the testing, spreading and scaling of innovations in sustainable care, using improvement methods.”

She adds that CASCADES will focus on encouraging health systems in Canada to work in a co-ordinated way to achieving net-zero emissions. While there have been “pockets of extraordinary excellence and effort,” it has often been too piecemeal, she says.

Andrea MacNeill believes CASCADES is the right initiative to manage these limitations.

“We possess sustainability and health-care expertise, with deep connections with both sectors,” she says. “We understand how to engage diverse members of the health-care community on their own terms and pursue national co-ordination while respecting local priorities, provincial and territorial jurisdiction and differences across professions, practices and context.”

And Miller is pleased to report that there is “actually tremendous energy in the health-care sector around this. I think the appetite is really there. The timing of launching CASCADES is very good, given the urgency. People want to know how to bring this into their professional lives and how to be on the right side of history on this issue.”

A century after the discovery of insulin, ��TV and its hospital and industry partners have built a culture of discovery, innovation and collaboration that has transformed health care and continues to have a ripple effect worldwide. This article is part of a series featuring researchers working on medical and health innovations for the future.

'A Swiss Army knife': Daniel Drucker bets the gut hormone GLP-1 can be used to treat far more than diabetes

Christopher.Sorensen — Wed, 03 Nov 2021 14:28:07 +0000

'A Swiss Army knife': Daniel Drucker bets the gut hormone GLP-1 can be used to treat far more than diabetes

Christopher.Sorensen Wed, 11/03/2021 - 10:28

Cutline

A pioneer of gut hormone research that led to therapies for type 2 diabetes, obesity and short bowel syndrome, Daniel Drucker is investigating whether the same hormones can help treat everything from heart disease to Alzheimer's (photo by Johnny Guatto)

Brianne Tulk

Topic

Mount Sinai Hospital

Research & Innovation. Faculty of Arts & Science

Daniel Drucker is unraveling a medical mystery.

Drucker, a professor in the department of medicine at the University of Toronto’s Temerty Faculty of Medicine and a senior scientist at the Lunenfeld-Tanenbaum Research Institute at Sinai Health, has pioneered research on gut hormones that has led to life-changing therapies for people with type 2 diabetes, obesity and short bowel syndrome.

Now, Drucker’s lab is studying how these same hormones work in the context of other conditions throughout the body, which could result in treatments for an even wider variety of diseases.

Drucker, an inductee to the Canadian Medical Hall of Fame and winner of the Canada Gairdner International Award, is most well-known for his contributions to the discovery of glucagon-like peptides (GLP-1 and GLP-2), gut hormones that help control insulin and balance blood sugar levels, and for the development of related therapies for diabetes, obesity and intestinal failure.

Yet, beyond conventional metabolism, drugs based on GLP-1 can also reduce plaque formation in arteries, or atherosclerosis, and control inflammation in several organs. Plaque and inflammation are linked to heart attack, stroke and other cardiovascular diseases – some of the leading causes of death in people with type 2 diabetes and obesity.

The drugs also show promise for treating liver disease and Alzheimer’s disease.

In a study recently published in JCI Insight, Drucker’s research team investigated the role that specific GLP-1 receptors play to make GLP-1 drugs effective against cardiovascular and liver disease in the aorta and liver of mice.

In the first half of the study, Drucker’s team saw that the GLP-1 drug reduced plaque in the arteries, but the presence or lack of the GLP-1 receptor in blood vessel and immune cells in the aorta did not play a role.

“We’ve ruled out the importance of receptors in these cell types, but we still don’t fully understand how GLP-1 reduces atherosclerosis," says Drucker.

This negative result was valuable, but the second story the paper told was more novel.

The mice developed fatty liver disease, liver fibrosis and liver inflammation through the same high-fat diet that triggered plaque development in their arteries. The researchers saw that the mice with GLP-1 receptors in specific cells in their livers responded well to the GLP-1 drugs, whereas the “knockout” mice without the GLP-1 receptor in these cells did not – despite both groups losing weight as an effect of the GLP-1 drug.

This outcome suggests that even though weight loss has conventionally been important for GLP-1 action to reduce fat and inflammation in the liver, it may not be the whole story. In, fact GLP-1 may reduce liver inflammation through mechanisms independent of weight loss.

“This paper is the first to show that even though weight loss is the same in both groups of animals that we studied, the animals that were missing the GLP-1 receptor in the immune cells in the liver did not have the same therapeutic benefit,” Drucker says. “It's really the first paper to show that there's another element to the story of how GLP-1 works in the liver.”

GLP-1 drugs are already in phase three trials to treat liver diseases such as non-alcoholic steatohepatitis, a more aggressive form of fatty liver disease. So, it was not surprising for the researchers to see that mice treated with GLP-1 drugs saw reduced liver inflammation.

But Drucker said it was exciting to identify GLP-1 receptors in specific immune cells in the liver, which may be necessary to get the full therapeutic effects of GLP-1 drugs to treat fatty liver and liver inflammation. This finding could lead to more targeted and effective treatment options.

Overall, the study is another piece in the puzzle of how GLP-1 works in different areas of the body. But researchers still need a better understanding of how GLP-1 drugs produce their multiple therapeutic benefits in treating diseases.

“If I could figure out how GLP-1 reduces heart attacks and strokes, and I knew where that magic was happening, maybe we could make even better, more targeted GLP-1 therapies to produce more effective medicines,” Drucker says.

Drucker credits his background as a clinician scientist for bringing the perspective of patients and their unmet medical needs into his research. Although he hasn’t been directly involved in patient care for 12 years, he calls his training as a physician and a clinician scientist the “secret sauce” to his research.

“What clinician scientists are really good at is asking the important questions that are directly relevant to human disease,” he says. “I’ve always tried to ask questions that are not just interesting for the sake of basic science, which is important by itself, but also questions that might inform how disease pathophysiology and drugs work clinically.”

He says that what makes the GLP-1 story so exciting is that physicians are able to treat diabetes and obesity by conventionally lowering blood sugar or bodyweight, but also by attacking cardiovascular risk, the number-one cause of death these patients face.

“Until recently, there haven't been therapies that go beyond lowering blood sugar or reducing bodyweight to actually show there's a reduction in death,” Drucker says. “GLP-1 therapies are changing the natural history of these diseases.”

Improved disease outcomes may soon extend to other conditions. Emerging data suggest that GLP-1 drugs have an anti-inflammatory effect to treat a wide variety of diseases, and the next frontier could be Alzheimer’s disease now that GLP-1 drugs targeting the condition recently entered phase three trials.

Drucker says that if GLP-1 drugs work to treat Alzheimer’s, it would likely reflect a combination of neuroprotection, improved brain metabolism and reduction of inflammation associated with the condition, which could also improve cognition and slow the course of disease.

“Whether it’s in the pancreas, blood vessels, the liver, or the brain, increased inflammation is a driving component of the pathology of all kinds of different diseases,” he says. “I believe that one reason GLP-1 is the Swiss Army knife of metabolism – that it can do so many different things in so many different organs – is its ability to reduce inflammation.”

Exactly how that happens, however, is still shrouded in mystery, Drucker says.

“There’s a huge amount of uncertainty as to how GLP-1 controls inflammation in different organs in the body, and that’s a major focus for our lab right now.”

��TV researchers' lab-grown muscles used to study Duchenne muscular dystrophy, develop treatments

lanthierj — Mon, 25 Oct 2021 19:39:11 +0000

��TV researchers' lab-grown muscles used to study Duchenne muscular dystrophy, develop treatments

lanthierj Mon, 10/25/2021 - 15:39

Cutline

��TV researchers Penney Gilbert and Bryan Stewart obtained cells from people living with Duchenne muscular dystrophy to grow miniature muscles that are being used to develop new treatments for the genetic disorder (photo by Johnny Guatto)

Topic

Donnelly Centre for Cellular & Biomolecular Research

Biology

University of Toronto Mississauga

Inside a Petri dish in a lab at the University of Toronto is a muscle – made from scratch using human stem cells – that has Duchenne muscular dystrophy (DMD).

To study the biological properties of DMD, a degenerative muscle disorder that mainly affects males, ��TV researchers obtained cell lines from people living with the condition and used them to create miniature muscles in a dish. Now, they’re helping other researchers and industry partners develop and test new treatments that may help the boys and young men who are afflicted with DMD.

The research team is led by Bryan Stewart, professor of biology at ��TV Mississauga, and Penney Gilbert, associate professor in the Institute of Biomedical Engineering and at ��TV’s Donnelly Centre for Cellular & Biomolecular Research. Stewart specializes in the physiology of neurons and muscles. Gilbert, a cell biologist, specializes in restoring skeletal muscle (the muscles attached to bone) by using stem cells. They decided to collaborate after meeting at a research leadership workshop organized by University Professor Molly Shoichet about six years ago.

“We learned we were both studying skeletal muscle,” says Gilbert. “Bryan’s lab was using fruit flies to understand the muscle-nerve connection, which enables the brain to tell, for example, our arm to move.

“My lab was creating human tissue to make models of the muscle-nerve connection. Together, we realized our unique tools and methods could enable us to look at DMD in a different way from, literally, any group in the world.”

DMD is caused by a gene mutation that prevents the body from producing dystrophin, the protein that enables muscles to function. It is a rare condition – occurring in one out of 3,500 to 5,000 male children worldwide – but it is devastating. Starting around age five, DMD progressively damages and weakens the muscles, including the heart. Most children with DMD will have to use a wheelchair. And most will die before they reach 30.

Gilbert says the biomedical innovation of creating muscle “means that for the first time ever it is actually possible to study DMD and the nerve-muscle connection outside of the body.

“This gives us the opportunity to revisit observations that had been made decades ago that seemed to suggest that the muscle-nerve connection in DMD might be impaired,” she says. “Now, we will see if this can be observed in our model. And if we do see it, could we try to use that as a starting point to find molecules that might improve the muscle-nerve connection?”

The team is working to make its 3D muscle models more representative of what is actually found in humans. They are especially paying attention to the variation in muscle structure and function that can exist in people who have DMD. Gilbert and Stewart note the expertise brought to the work by post-doctoral researchers Christine Nguyen and Majid Ebrahimi.

Stewart emphasizes that while the team is not directly creating drugs or therapies, their work will be an important foundational system for other researchers to use in developing pharmaceutical treatments or for testing the gene therapy experiments that will soon move to clinical trials.

Michael Rudnicki, a noted Canadian stem cell expert, agrees.

“The DMD pre-clinical assays being developed by Gilbert and Stewart are a critical facet of the translational pipeline, making it possible to test current and future therapeutics in the context of human cells,” says Rudnicki, senior scientist and director of the regenerative medicine program and Sprott Centre for Stem Cell Research at the Ottawa Hospital Research Institute.

“There is a wealth of great work being done on DMD around the world,” says Stewart. “Penney and I knew when we met at that workshop that there could be a lot of power in merging our two groups.

“I think we are at a point where we can help to launch a new surge in testing and discovery that will begin to benefit the people and families living with DMD.”

Cloaking technology: Helping therapeutic cells evade your immune system

lanthierj — Fri, 08 Oct 2021 10:57:51 +0000

Cloaking technology: Helping therapeutic cells evade your immune system

lanthierj Fri, 10/08/2021 - 06:57

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Andras Nagy (Photo provided by Sinai Health Foundation)

Topic

Breaking Research

Institutional Strategic Initiatives

Toronto General Hospital

Medicine by Design

Mount Sinai Hospital

University Health Network

Stem Cells

Stem cell pioneer Andras Nagy has a way of describing the work of your immune system: “It’s surveillance inside our body.”

That surveillance does us good when harmful bacteria or viruses enter our body. The immune system releases fighter cells to kill the invaders.

But regenerative medicine therapies often involve transplanting tissues or cells into a person. When new heart or pancreatic cells are transplanted, for example, the immune system will see these good things as enemies and reject them. Drug treatment can be used to suppress this immune response, but it can leave the person open to serious infection.

Nagy, a professor in the department of obstetrics and gynaecology at the University of Toronto's Temerty Faculty of Medicine and a senior investigator at Sinai Health System’s Lunenfeld-Tanenbaum Research Institute, and his research team have been experimenting with a process called “cloaking,” which he believes could be used to hide therapeutic cells from the immune surveillance system and allow them to do their good work.

Though this research will one day be applicable to all cell therapies, Nagy’s team is currently testing the cloaking technology with insulin-secreting pancreatic cells that are made from stem cells and could be a powerful cell therapy for type 1 diabetes.

Stem cells are cells that can be reprogrammed and turned into an unlimited source of any type of human cell needed for treatment. Nagy notes that the first years of stem cell research were at the basic science level, as scientists worked to understand the nature of stem cells. He says about 10 years ago, there was a notable shift to what he calls “translational” research. His work is part of this wave of applied science; in fact, in 2015 he co-founded a biotech company, panCELLa Inc., to make his cell technologies widely available.

“Regenerative medicine is at a point now where we can translate our research into therapies that can help all humankind,” he says.

The Canada Research Chair in Stem Cells and Regeneration, Nagy says that researchers have long known that transplanted cells and tissues can be attacked by the immune system.

“We wondered if there was a way to hide or ‘cloak’ these good cells, so the immune response wouldn’t destroy them,” says Nagy. “But before we could move into that we had to deal with a significant hurdle – the safety of the implanted cells.”

Nagy points out that when these new cells are created, there is a chance they could mutate and become cancerous. The more cells needed for a therapy, the more cell divisions that take place, meaning a higher chance of mutation and cancer.

In earlier research, partially funded by a previous Medicine by Design team projects award, Nagy published a paper in Nature that described a “fail safe” cell technology that he and his team devised that can increase the safety of a cell graft and has a formula to quantify the risk of mutation so that people can make an informed decision on whether such a risk is acceptable to them.

The fail-safe system is a switch that eliminates potentially dangerous cells during cell therapy. The switch is introduced into stem cells, which are then turned into the therapeutic cells. The switch is turned on by a drug that can be added to the cell graft or applied directly into the body after transplant.

Nagy says the killer switch is fail safe because it is composed of two genes, one required for division and one that can trigger cell suicide, stitched together. If a mutated gene begins dividing, the drug is there to activate the kill switch and kill the cell. And if the cell loses the switch, it also loses the ability to multiply.

With the important first step of creating the fail safe switch done, Nagy turned to the cloaking, work that is supported by his team’s current Medicine by Design team projects award.

Nagy’s team is one of 12 sharing nearly $21 million in funding from Medicine by Design over three years. Funded by a $114-million grant from the Canada First Research Excellence Fund, Medicine by Design is an institutional strategic research initiative that is working at the convergence of engineering, medicine and science to catalyze transformative discoveries in regenerative medicine and accelerate them toward clinical impact.

“Medicine by Design has been really important in supporting scientists in bringing the possibilities of regenerative medicine to patients. I’m grateful to Medicine by Design for funding the high-risk and high impact projects that many other funding agencies often say are just too ambitious.”

The cloaking technology involves turning off certain genetic switches in the cells created from stem cells to avoid detection by the immune system. This work was supported by findings from a devastating cancer found in Tasmanian devils, the marsupial native to the Australian state of Tasmania.

Between 1996 and 2015, 95 per cent of the Tasmanian devil population was wiped out as a result of contagious facial cancer cells transmitted when the devils bit each other. Nagy’s research found that the cancer had a way of cloaking itself from the devils’ immune system, which backed up his theory that cells could be hidden from the immune system.

Nagy identified eight genes that are central to immunity. He reasoned that just as the Tasmanian devils’ facial cancer could avoid detection by turning off the right genetic switches, his stem cell-derived cells could similarly become cloaked. Scientists in Nagy lab have been testing the cloaking in mice with encouraging results.

Sara Vasconcelos

Working with Nagy are Maria Cristina Nostro, senior scientist at the University Health Network’s (UHN) McEwen Stem Cell Institute and associate professor, department of physiology at ��TV; and Sara Vasconcelos, scientist at the UHN’s Toronto General Hospital Research Institute and associate professor at ��TV’s Institute of Biomedical Engineering.

The Nostro lab’s focus is to generate insulin-secreting pancreatic cells from stem cells. These cells could one day have the potential to treat patients with type 1 diabetes. Nostro works closely with Vasconcelos, whose lab focuses on helping to keep the transplanted cells alive once they enter the body. Cells need oxygen and other nutrients, which are delivered through the blood vessels.

Together, the team is testing ways to integrate Nagy’s technologies into Nostro’s functional pancreatic cells. Vasconcelos’s aim is for these therapies to survive in the body.

“When you just transplant the cells, they don’t have blood vessels, so they’ll die, independent of whether the immune system kills them or not. If they die, we’ll never know if it was the immune system or lack of oxygen,” Vasconcelos says. The Vasconcelos lab team repurposes small vessels, which exist in fat. They then use the vessels as units to increase blood flow and allow the cells to engraft and survive after they have been transplanted.

Nagy says the combination of the fail safe and cloaking technologies will make for a powerful therapy. “On the one hand, we can now introduce good cells into recipient’s body that can be hidden from the immune response and do the work they were intended to do. And that means doctors won’t have to use immunosuppression drugs. Finally, if one of the newly created cells is cancerous to the patient, our safe-cell technology can kill it or at least give us information on risk that we can communicate to the patient.”

When stem cell-derived therapies are created for individual patients, Nagy says, it is expensive, costing hundreds of thousands of dollars per patient. Nagy envisions turning his cells that combine fail safe and immune cloaking technologies into “off-the-shelf” products that can be used by anyone and are inexpensive.

Nagy has been building a notable research career in regenerative medicine since he came to Canada from Hungary in 1989, initially joining the lab of renowned researcher and University Professor Janet Rossant at the Samuel Lunenfeld Research Institute (now the Lunenfeld-Tannenbaum Research Institute) at Mount Sinai Hospital.

With a focus on skin cells, ��TV's Michael Sefton seeks 'huge step forward' in diabetes treatment

Christopher.Sorensen — Wed, 25 Aug 2021 16:29:55 +0000

With a focus on skin cells, ��TV's Michael Sefton seeks 'huge step forward' in diabetes treatment

Christopher.Sorensen Wed, 08/25/2021 - 12:29

Cutline

Michael Sefton, a ��TV tissue engineer and executive director of Medicine by Design, is investigating whether dendritic skin cells can aid in the successful transplantation of insulin-producing islet cells in diabetes patients (photo by Neil Ta)

Topic

Princess Margaret Cancer Centre

Donnelly Centre for Cellular & Biomolecular Research

Chemical Engineering

Faculty of Applied Science & Engineering

Medicine by Design

University Health Network

Can dendritic cells found in the skin be an important piece of the puzzle of enabling stem cell transplants for diabetes?

Michael Sefton, a renowned University of Toronto tissue engineer, is confident enough about the possibility that – with support from the type 1 diabetes non-profit JDRF – he is about to launch a major new chapter in his research.

The work will build on a finding from a research team at the University of Alberta in 2000 that proved islet cells (also called islets of Langerhans), which produce insulin and are found in the pancreas, could be transplanted from a donor into the livers of people living with type 1 diabetes. The patients who were treated saw their diabetes disappear for long periods of time and no longer needed to inject insulin. The procedure came to be known as the Edmonton Protocol.

“It was a huge finding from that group,” says Sefton, who is executive director of Medicine by Design and University Professor in the department of chemical engineering and applied chemistry and the Institute of Biomedical Engineering in the Faculty of Applied Science & Engineering. “But the problem was the liver. It was a hostile environment to those new cells and mounted an immune response that killed many of them and the patients’ diabetes returned eventually.”

Nevertheless, it got Sefton thinking: What if there was a better place to implant the cells?

He thought of the skin. Research had proven that the skin – or just under it – is an area less likely to be hostile to transplanted cells such as pancreatic cells. Not only that, but implanting cells under the skin is less invasive than doing so in the liver. The cells could be retrieved more easily, which might make the therapy safer for the patient

But the method raised another problem. The skin has too few blood vessels to enable the implanted cells to survive and enable the body to manage blood sugar. Could scientists find a way to create blood vessels?

In 2016, JDRF awarded Sefton more than $1 million to explore the possibility. To create the blood vessels, the Sefton team used a material that contained methacrylic acid (MAA).

“Once we insert a polymer gel with MAA under the skin, the MAA interacts with the living system in the body (mice are currently being used) and it creates the blood vessels,” Sefton says. “We’re just beginning to understand how MAA works. And this enables the implanted pancreatic cells to deliver insulin throughout the body to do its work in controlling blood sugar and, thus, stopping the diabetic condition.”

Another major hurdle was obtaining enough pancreatic cells for transplant. Sefton, whose lab is located at the Donnelly Centre for Cellular and Biomolecular Research, says about a million pancreatic islets (each islet contains about a thousand cells) were needed for each patient treated through the Edmonton Protocol model. Acquiring the islets often required two donors.

But now, Sefton says, scientists such as Maria Cristina Nostro – a senior scientist at McEwen Stem Cell Institute, University Health Network, who is also a Medicine by Design-funded researcher and an associate professor of physiology at the Temerty Faculty of Medicine – can create insulin-producing cells from stem cells, which provides an unlimited supply.

With these big problems solved, the team still has another one to deal with – the immune response that the body mounts when the new pancreatic cells are transplanted.

The body’s natural response is to reject, say, a new heart or kidney. It’s the body going after what it perceives to be an invader, in the same way the immune system attacks harmful bacteria or viruses that have entered the body.

While, as Sefton says, the skin tends to respond differently than the liver, there will still be a response enacted that will try to reject the transplanted pancreatic islets once implanted.

This is where Sefton believes the dendritic cells can play an important role.

Discovered by German pathologist Paul Langerhans (the same scientist who also discovered the pancreatic islets named for him) in 1869, dendritic cells are powerful immune cells found in the skin.

“They will, of course, mount an immune response once we implant the pancreatic islets,” Sefton says. “But we believe that the MAA has properties that will work on the skin’s dendritic cells to be tolerant of the pancreatic cells. We don’t want to suppress the immune system because that is dangerous for the patient.

“We want to fool it into accepting the new pancreatic cells as if they are part of the patient’s body. And if we can do that, we’ll have taken a huge step forward.”

Sefton and his team will use the new JDRF grant over the next two years to continue to explore this hunch.

Adventurous health science research isn’t new to Sefton, who has built a record for innovation in biomedical research that has earned him global respect.

He was named a University Professor in 2003, the highest honour ��TV bestows on its faculty. In 2017, he was honoured with the Order of Canada for his leadership in biomedical engineering. Before joining Medicine by Design, he was director of ��TV’s Institute of Biomedical Engineering and boasts many scientific achievements as a scientist, including being among the first to combine living cells with polymers and effectively launching the field now called tissue engineering.

Today, as the executive director of the Medicine by Design strategic research initiative, Sefton speaks with both pride and excitement about the work of scientists tackling difficult health challenges using regenerative medicine, a branch of health research and treatment that has exploded globally since stem cells were discovered by ��TV scientists James Till and Ernest McCulloch at Toronto’s Princess Margaret Hospital – now Princess Margaret Cancer Centre – in 1961.

“The hallmark of our approach is the convergence of scientists from a multitude of disciplines across the University of Toronto and our nine partner research hospitals,” he says. “We’ve got biologists, biochemistry experts, physicists, engineers and specialists in all aspects of medicine working together and sharing ideas. Our goal is to think way beyond the obvious and to act boldly in finding ways to improve treatment and maybe even cure major diseases.”

Medicine by Design was founded in 2015 with a $114 million from the Canada First Research Excellence Fund. The projects in Medicine by Design’s portfolio focus on using stem cells as living therapies, harnessing the body’s capacity for repair, disabling the triggers of disease and creating technologies to advance regenerative medicine.

Within that slate of exploration, Medicine by Design research teams are making progress on treating a multitude of diseases such as restoring vision lost to age-related macular degeneration, using stem cells to treat diseased livers in patients who have no hope of a liver transplant, stopping dangerous and hard-to-diagnose abdominal aortic aneurysms before they do their damage and creating methods to help the brain repair itself after stroke.

“We place a huge emphasis on new ideas and research that is risky,” says Sefton. “That’s the way you have to think when you want to really change things. I want people to hear about our work and think that what we are trying to achieve is impossible. l believe firmly that when it comes to disease, we don’t have to just accept what nature gives us with, say, cancer or stroke or diabetes. We can do better than nature.”

He also emphasizes that advances in technology are essential components of enabling breakthroughs. He points to the importance of tools like CRISPR, a powerful gene editing technology that won the Nobel Prize for Emmanuelle Charpentier and Jennifer Doudna in 2020 for creating opportunities that were unthinkable even 30 years ago.

“That’s why I say that 30 years from now, regenerative medicine will be at the centre of how we treat disease,” says Sefton. “It will be standard practice and it will be giving us a level of health we would have never thought possible.

“We may well be able to even eliminate many diseases.”

New study uncovers evolutionary forces in aging of blood system and increased risk of cancer

geoff.vendeville — Fri, 20 Aug 2021 14:42:03 +0000

New study uncovers evolutionary forces in aging of blood system and increased risk of cancer

geoff.vendeville Fri, 08/20/2021 - 10:42

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Professor Philip Awadalla Photo courtesy of OICR)

Hal Costie

Topic

Breaking Research

Ontario Institute for Cancer Research

Donnelly Centre for Cellular & Biomolecular Research

Cancer

Vector Institute

A new study by researchers at the University of Toronto and Ontario Institute for Cancer Research provides insight into why some people develop a type of leukemia while others do not, despite an age-related increase in blood cells that replicate with genetic mutations.

Their findings, published in Nature Communications last week, have the potential to significantly advance early detection and treatment of acute myeloid leukemia (AML), a fast-growing and often deadly cancer, by enabling clinicians to identify people at high risk for the disease.

The researchers found that an interplay of positive, neutral and negative evolutionary selection, which acts on mutations in blood stem cells during a process called age-related clonal hematopoiesis or ARCH, can lead to AML.

Negative or “purifying selection,” the researchers showed, was present in people who did not develop a malignancy, and thereby prevented disease-related cells from dominating the cell population.

“We have shown that the constellation of evolutionary forces at play within hematopoietic stem cells can be a robust indicator of those who are at increased risk of blood cancers such as AML,” said Philip Awadalla, a professor of molecular genetics at ��TV’s Temerty Faculty of Medicine and the director of computational biology at OICR. “Being able to accurately classify patients based on risk can allow for more frequent and intensive screening for those with ARCH mutations with a concerning evolutionary signature.”

The researchers computationally generated more than five million blood populations, trained a deep neural network model to recognize different evolutionary dynamics and employed the model to analyze blood samples that had undergone deep genomic sequencing.

Quaid Morris

These samples were from 92 individuals who went on to develop AML, and 385 who did not despite the presence of ARCH. The study is one of the first to use a single system of tools to capture the interaction of the multiple evolutionary forces at play in ARCH.

“The models we developed in this study can significantly increase the value of ARCH as a biomarker for blood malignancies,” said Quaid Morris, a computational biologist at Memorial Sloan Kettering Cancer Center in New York City, OICR associate and former professor at the Donnelly Centre for Cellular and Biomolecular Research. “Our team is looking forward to continuing to bolster our understanding of ARCH and seeing these advancements help patients.”

The researchers showed that these alternative evolutionary models were predictive of AML risk over time. Similarly, the tools enabled the team to identify genes where mutations that are damaging to stem cells can accumulate.

Kimberly Skead

“Our novel application of deep learning tools and population genetic models to genomic sequencing allowed us to classify the evolutionary interactions within a blood sample with a very high degree of accuracy,” said Kimberly Skead, the first author of the study and a doctoral candidate in molecular genetics at ��TV and the Vector Institute for Artificial Intelligence. “This level of resolution enabled us to understand how both positive and negative selection shape the aging blood system and to establish strong links to individual health outcomes, which bodes well for potential clinical use.”

Awadalla said it would be reasonable to anticipate future screening blood samples for early detection of disease and blood cancers. “With these tools, we can more proactively monitor people’s health,” he said. “Early detection of cancer is critical with respect to prevention and effectiveness of treatment.”

This research was supported by OICR, the Ontario Ministry of Colleges and Universities, Canadian Institutes of Health Research, Vector Institute for Artificial Intelligence, Natural Sciences and Engineering Research Council of Canada, Canadian Institute for Advanced Research, National Institutes of Health, Memorial Sloan Kettering Cancer Center, Canadian Data Integration Centre, Genome Canada, Ontario Genomics and ��TV.

Low-glycemic diet reduces cardiometabolic risks for people with diabetes: ��TV study

Christopher.Sorensen — Thu, 12 Aug 2021 16:54:53 +0000

Low-glycemic diet reduces cardiometabolic risks for people with diabetes: ��TV study

Christopher.Sorensen Thu, 08/12/2021 - 12:54

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(Photo by Sharon Pittaway via Unsplash)

Topic

Alumni

Nutritional Sciences