Princess Margaret Cancer Centre

Institutional Strategic Initiatives

Acceleration Consortium

Donnelly Centre for Cellular & Biomolecular Research

Artificial Intelligence

Faculty of Applied Science & Engineering

Robotics

Subheadline

The Self-Driving Laboratory for Human Organ Mimicry is one of six self-driving labs launched by the Acceleration Consortium to drive research across a range of fields

The UUֱ�� is home to a new “self-driving lab” that will allow researchers to better understand health and disease – and to more rapidly test the efficacy and toxicity of new drugs and materials.

Based at the Donnelly Centre for Cellular and Biomolecular Research, the Self-Driving Laboratory for Human Organ Mimicry is the latest self-driving lab to spring from a historic $200-million grant from the Canada First Research Excellence Fund to the Acceleration Consortium – a global effort to speed the discovery of materials and molecules that is one of several UUֱ�� institutional strategic initiatives.

The new lab will be led by Milica Radisic, Canada Research Chair in Organ-on-a-Chip Engineering and professor of biomedical engineering in the Faculty of Applied Science & Engineering, and Vuk Stambolic, senior scientist at the Princess Margaret Cancer Centre, University Health Network, and a professor of medical biophysics in the Temerty Faculty of Medicine.

“The lab will innovate new complex cellular models of human tissues, such as from the heart, liver, kidney and brain, through stem-cell-derived organoids and organ-on-a-chip technologies,” said Radisic. “In partnership with the Princess Margaret Cancer Centre, the lab will also enable automation of patient-derived tumour organoid cultures to accelerate the discovery of new cancer treatments.”

Tumour organoids stained with fluorescent dyes (image courtesy of Nikolina Radulovich and Laura Tamblyn)

The Self-Driving Laboratory for Human Organ Mimicry is one of six self-driving labs launched by the Acceleration Consortium at UUֱ�� to drive research across a range of fields, including materials, drug formulation, drug discovery and sustainable energy.

How does a self-driving lab work? Once set up, it runs with robots and artificial intelligence performing as much as 90 per cent of the work. That, in turn, speeds up the process of discovery by freeing researchers from the tedious process of trial and error so they can focus on higher-level analysis.

“The Self-Driving Lab for Human Organ Mimicry will enable other self-driving labs to develop new materials and drugs by rapidly determining their efficacy, as well as their potential toxic effects and other impacts on human tissues,” said Stambolic. “While animal testing is typically the go-to method to assess the safety of new molecules made for humans, this lab will replace trials involving animals with organoids and organs-on-chips. This will allow us to advance to human clinical trials much more quickly.”

Professors Milica Radisic and Vuk Stambolic (supplied images)

“The goal of our self-driving labs is to use AI to move the discovery process forward at the necessary pace to tackle global issues,” said Alán Aspuru-Guzik, director of the Acceleration Consortium and professor of chemistry and computer science in the Faculty of Arts & Science. “The Human Organ Mimicry SDL, as well as other self-driving labs launched through the Acceleration Consortium, will establish UUֱ�� and our extended research community as a global leader in AI for science.”

Donnelly Centre Director Stephane Angers says the centre is an ideal environment for the new lab, citing the the international hub for cross-disciplinary health and medical research’s reputation as a hotspot for technological innovation – one that offers resources to the wider research community.

“The Donnelly Centre is a thriving research community because it was founded on the principle of interdisciplinary collaboration,” said Angers, a professor of biochemistry and pharmaceutical sciences. “Our research strengths in computational biology, functional genomics and stem cell biology will catalyze the development and success of the Self-Driving Lab for Human Organ Mimicry.”

The launch of the new lab will also expand the Donnelly Centre’s team of experts with the hiring of five new staff who will work to make the self-driving lab fully automated. The lab is expected to be operational by the end of the year

“The Donnelly Centre is one of the foremost research institutes in the world, with outstanding strength in genomics, model organisms, organoids, computational biology and many other areas,” said Justin Nodwell, vice-dean of research and health science education at the Temerty Faculty of Medicine.

“I’m delighted to hear about the addition of the Acceleration Consortium’s artificial intelligence-powered self-driving lab to the centre’s existing technical base. It will facilitate new lines of research by some of the best minds in the country.”

Why is COVID-19 more severe in some people? Researchers use genetics, data science to find out

Christopher.Sorensen — Wed, 25 Oct 2023 14:08:53 +0000

Why is COVID-19 more severe in some people? Researchers use genetics, data science to find out

Christopher.Sorensen Wed, 10/25/2023 - 10:08

Cutline

(Photo by Cole Burston/AFP/Getty Images)

Tyler Irving

Topic

Institutional Strategic Initiatives

COVID-19

Data Sciences Institute

Sunnybrook Health Sciences Centre

Sinai Health

Dalla Lana School of Public Health

Unity Health

Computer Science

Faculty of Arts & Science

Hospital for Sick Children

Mount Sinai Hospital

St. Michael's Hospital

Statistical Sciences

Institute of Biomedical Engineering

Women's College Hospital

Subheadline

With the help of UUֱ��'s Data Sciences Institute, researchers from the university and partner hospitals gathered more than 11,000 full genome sequences from across Canada

Why do some people have a more severe course of COVID-19 disease than others? A genome sequence database created by an international collaboration of researchers, including many from the UUֱ�� and partner hospitals, may hold the answers to this question – and many more.

The origins of the Canadian COVID-19 Human Host Genome Sequencing Databank, known as CGEn HostSeq, can be traced to the earliest days of the pandemic.

Lisa Strug, senior scientist at The Hospital for Sick Children (SickKids) and academic director of UUֱ��’s Data Sciences Institute, one of several UUֱ�� institutional strategic initiatives, says genetic data was top of mind for her and other researchers in late 2019 and early 2020 as reports of a novel form of coronavirus emerged from China and then other locations across the globe.

Lisa Strug (Photo courtesy The Hospital for Sick Children)

“In my research, I use data science techniques to map the genes responsible for complex traits,” says Strug, who is a professor in UUֱ��’s departments of statistical sciences and computer science in the Faculty of Arts & Science and in the biostatistics division of the Dalla Lana School of Public Health.

“We knew that genes were a factor in the severity of previous SARS infections, so it made sense that COVID-19, which is caused by a closely related virus, would have a genetic component, too.

“Very early on, I started getting messages from several scientists who wanted to set up different studies that would help us find those genes.”

Over the next few months, Strug – who is also the associate director of SickKids’ Centre for Applied Genomics, one of three sites across Canada that form CGEn, Canada’s national platform for genome sequencing infrastructure for research – collaborated with nearly 100 researchers from across UUֱ�� and partner hospitals and institutions, as well as other researchers from across Canada to enrol individuals with COVID-19 and sequence their genomes.

Some of the key team members from the Toronto community included:

Stephen Scherer, chief of research at SickKids Research Institute and a University Professor in UUֱ��’s Temerty Faculty of Medicine, as well as director of the UUֱ�� McLaughlin Centre
Rayjean Hung, associate director of population health at the Lunenfeld-Tanenbaum Research Institute, Sinai Health, and a professor in UUֱ��’s Dalla Lana School of Public Health
Angela Cheung, clinician-scientist at University Health Network, senior scientist at Toronto General Hospital Research Institute and a professor in UUֱ��’s Temerty Faculty of Medicine
Upton Allen, head of the division of infectious diseases at SickKids and a professor in UUֱ��’s Temerty Faculty of Medicine

The projected was initiated by Scherer and CGEn’s Naveed Aziz, along with Strug, and a $20-million grant was secured from Innovation, Science and Economic Development Canada, administered through Genome Canada.

“We had to go right to the top to get this project funded fast and our labs and teams worked seven days a week on the project right through the pandemic,” Scherer recalls.

Identifying associations between individual genes and complex traits typically requires thousands of genomes – both from those with the trait and those without. Though there was no shortage of cases to choose from, it was critical to gather and sequence DNA – and then organize the data in a way that would be ethical, efficient and useful to researchers now and in the future.

“One of our key mandates at the Data Sciences Institute is developing techniques and programs that ensure that data remains as open, accessible and as re-producible as it can be,” Strug says.

“That vision was brought to bear as we assembled the data infrastructure for this project – for example, ensuring that consent forms were as broad as possible so that this data could be linked with other sources, from electronic medical records to other health databases.

“We wanted to be sure that even after the COVID-19 pandemic was over this could be a national whole genome sequencing resource to ask all kinds of questions about health and our genes. The development of the database and its open nature also enabled Canada to collaborate effectively with similar projects in other countries.”

Partner hospitals and institutions:

The Hospital for Sick Children (SickKids)
Lunenfeld-Tanenbaum Research Institute, Sinai Health
Mount Sinai Hospital, Sinai Health
St Michael’s Hospital, Unity Health Toronto
University Health Network (UHN)
Princess Margaret Cancer Centre, UHN
Ontario Institute for Cancer Research
Women’s College Hospital
Toronto General Hospital, UHN
Baycrest Health Sciences

In the end, the project gathered more than 11,000 full genome sequences from across Canada, representing patients with a wide range of health outcomes. Those data were then combined with even more sequences from patients in other countries under what came to be called the COVID-19 Host Genetics Initiative.

It didn’t take long for patterns to start to emerge. A paper published in Nature in 2021 identified 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19.

Since then, even more data have been added, and subsequent analysis has confirmed the significance of existing loci while also identifying new ones. The most recent update to the project, published in Nature earlier this year, brings the total number of distinct, genome-wide significant loci to 51.

“Identification of these loci can help one predict who might be more prone to a severe course of COVID-19 disease,” says Strug.

“When you identify a trait-associated locus, you can also unravel the mechanism by which this genetic region contributes to COVID-19 disease. This potentially identifies therapeutic targets and approaches that a future drug could be designed around.”

While it will take many more years to fully untangle the effects of the different loci that have been identified, Strug says that the database is already showing its worth in other ways.

“It can be difficult to find datasets with whole genome sequence and approved for linkage with other health information that are this large, and we want people to know that it is open and available for all kinds of research well beyond COVID through a completely independent data access committee,” she says.

“For example, several investigators from across Canada have been approved to use these data and we’ve even provided funding to trainees to encourage them to develop new data science methodologies or ask novel health questions using the CGen HostSeq data.”

“This was a humongous effort, where researchers from across Canada came together during the COVID-19 pandemic to recruit, obtain and sequence DNA from more than 11,000 Canadians in a systematic, co-operative, aligned way to create a made-in-Canada data resource that will hopefully be useful for years to come. I think that was really miraculous.”

Researchers challenge long-standing theory guiding nanoparticle treatment of tumours

Christopher.Sorensen — Mon, 25 Sep 2023 13:25:30 +0000

Researchers challenge long-standing theory guiding nanoparticle treatment of tumours

Christopher.Sorensen Mon, 09/25/2023 - 09:25

Cutline

PhD student Matthew Nguyen and Professor Warren Chan found that about 45 per cent of nanoparticles that accumulate in tumours end up exiting them (supplied photos)

Anika Hazra

Topic

Breaking Research

Donnelly Centre for Cellular & Biomolecular Research

Cancer

Faculty of Applied Science & Engineering

University Health Network staff

Subheadline

Study could explain why some cancer treatments are struggling in clinical trials

Researchers at the UUֱ�� have developed a new theory to explain how nanoparticles enter and exit the tumours they are meant to treat, potentially rewriting an understanding of cancer nanomedicine that has guided research for nearly four decades.

The Enhanced Permeability and Retention (EPR) effect, a concept largely unchallenged since the mid-1980s, posits that nanoparticles enter a tumour from the bloodstream through gaps between the endothelial cells that line its blood vessels – and then become trapped in the tumour due to dysfunctional lymphatic vessels.

“The retention aspect of the EPR theory is contingent on the lymphatic vessel cavity being too small for nanoparticles to exit, thereby helping nanoparticles that carry cancer-fighting drugs to stay in the tumours,” said Matthew Nguyen, a PhD student in the Institute of Biomedical Engineering in the Faculty of Applied Science & Engineering and the Donnelly Centre for Cellular and Biomolecular Research,

“But we found around 45 per cent of nanoparticles that accumulate in tumours will end up exiting them.”

Nguyen, who is a member of the lab of Professor Warren Chan, is the lead author on a new study that challenges the long-standing theory that was recently published in the journal Nature Materials. The researchers’ findings help explain why treatments based on the EPR effect are failing in clinical trials, building on earlier research from the Chan lab that showed less than one per cent of nanoparticles actually reach tumours.

Schematic of nanoparticle exit via the intratumoural lymphatic vessels. Nanoparticles in the tumour move towards the lymphatic vessel, cross the vessel wall and drain into the vessel lumen (Nguyen, L.N.M., Lin, Z.P., Sindhwani, S. et al.)

The researchers found that, contrary to the EPR effect, nanoparticles can leave tumours through their lymphatic vessels. The exit method for a nanoparticle depends on its size, with larger ones (50-100 nanometres wide) more likely to leave through lymphatic vessels in the tumours, and smaller ones (up to 15 nanometres wide) more likely to leave through lymphatic vessels surrounding the tumours.

In rare cases, nanoparticles will exit through blood vessels.

Nanoparticle exit from tumours occurs through spaces in the lymphatic vessel walls and transport vesicles that carry them across these walls. The researchers showed that nanoparticles will re-enter the bloodstream following lymphatic drainage, and hypothesized that these nanoparticles will eventually return to the tumour for another opportunity to treat it.

Disproving the EPR effect was no easy feat. The Chan lab spent six years working to understand why nanoparticles do not accumulate in tumours effectively. Prior to this study, the lab focused on how nanoparticles enter tumours in the first place. Through this and other studies, the lab developed a competing theory to the EPR effect, called the Active Transport and Retention (ATR) principle.

Nguyen noted that the field of nanomedicine has evolved since the publication of the nanoparticle entry study in 2020. “We got more pushback from other researchers on that study compared to this one,” he said. “People have started to accept that the EPR effect is flawed.”

With nearly half of accumulated nanoparticles exiting tumours, mostly through lymphatic vessels, future research could address this issue through nanoparticle treatments that prevent lymphatic drainage.

“We are excited to have a better understanding of the nanoparticle tumour delivery process,” said Chan. “The results of these fundamental studies on nanoparticle entry and exit will be important for engineering nanoparticles to treat cancer.”

The study’s findings, if applied across the field of cancer nanomedicine, promise a new direction to improve our understanding of how nanoparticles can be used to treat tumours.

“Trying to translate cancer nanomedicine to the clinic is like a working with a black box – some drugs work, some don’t, and it’s difficult to know why,” said Gang Zheng, associate research director at the Princess Margaret Cancer Centre and a professor of medical biophysics in UUֱ��’s Temerty Faculty of Medicine who was not involved in the study.

“Chan’s dedication to better understanding the mechanisms of nanoparticle uptake and exit is shining light on these processes to help make our translation efforts more efficient and successful.”

The research was supported by the Canadian Cancer Society, the Canadian Institutes of Health Research, NanoMedicines Innovation Network and the Canada Research Chairs program.

Gelareh Zadeh, a neurosurgeon-scientist, recognized with Canada Gairdner Momentum Award

Christopher.Sorensen — Thu, 30 Mar 2023 15:50:07 +0000

Gelareh Zadeh, a neurosurgeon-scientist, recognized with Canada Gairdner Momentum Award

Christopher.Sorensen Thu, 03/30/2023 - 11:50

Cutline

Gelareh Zadeh, a researcher at University Health Network and UUֱ��, is one of two winners of the inaugural Gairdner Momentum Award for her work on the classification and treatment of brain tumours (photo courtesy of UHN StRIDe)

Topic

Gelareh Zadeh, a researcher at University Health Network and the UUֱ��, has been recognized with a 2023 Canada Gairdner Award for her work on the classification and treatment of brain tumours.

She is one of two winners of the inaugural Momentum Award, created by the Gairdner Foundation to recognize mid-career researchers who have made significant discoveries with the potential to improve human health.

“It is such an honour to receive this award from the Gairdner Foundation,” said Zadeh, a senior scientist at University Health Network and a professor of surgery in UUֱ��’s Temerty Faculty of Medicine.

“I attribute my success in large part to the highly skilled and integrated research and clinical teams that I work with at University Health Network. My team’s achievements in translational brain research simply would not be possible without the exceptional researchers, trainees, neuro-oncologists, surgical teams and patients that we work with every day.”

The Gairdners are Canada’s most prestigious honour for health-related research and have developed a reputation since their inception in 1957 as a precursor to the Nobel Prize, with roughly a quarter of Gairdner recipients later winning a Nobel.

Zadeh was recognized for her contributions to the understanding of brain tumours. Her work has led to a new molecular classification of meningiomas, one of the most common types of brain tumours – an advance that could produce more effective treatments, models for predicting patient outcomes and biomarkers of treatment response.

Her research integrates molecular, genomic and epigenomic techniques with experimental models of brain tumours to accelerate translational research.

Zadeh has also led international efforts to define the genomic landscape of neuronal tumours that have not been the focus of significant biological research, including schwannomas, peripheral nerve tumours and malignant peripheral nerve sheath tumours. These efforts have revealed novel fusion proteins and resulted in the molecular sub-classification of schwannomas.

Additionally, her team has identified two biological pathways that drive the progression of benign peripheral nerve tumours toward malignant sarcomas. These molecular pathways provide a better biological understanding of tumour transformation, but also offer targets that could be used to develop therapeutic strategies, including the repurposing of existing pharmaceuticals.

In collaboration with researchers at the Princess Margaret Cancer Centre, Zadeh has advanced the development of blood-based biomarkers that can help discriminate among different brain tumour types and potentially to track response to therapy and early recurrence of disease.

Zadeh holds the Dan Family Chair in the division of neurosurgery in UUֱ��’s department of surgery and is the first woman in Canada to be named neurosurgery chair. She is also the head of neurosurgery at Toronto Western Hospital and co-director of the Krembil Brain Institute. She leads a 30-member research team at Princess Margaret Cancer Centre.

Her other prestigious honours include the William E. Rawls Prize from the Canadian Cancer Society, the Top 25 Women of Influence Award, and the Ab Guha Award, which is jointly awarded by the Society of Neuro-Oncology and American Association of Neurological Surgeons.

The Gairdner Momentum Award comes with a $50,000 prize and will be presented during Gairdner Science Week in October 2023.

A version of this story originally appeared at University Health Network.

UUֱ�� mourns the death of Queen Elizabeth II, lowers flags to half-mast

Christopher.Sorensen — Thu, 08 Sep 2022 23:35:48 +0000

UUֱ�� mourns the death of Queen Elizabeth II, lowers flags to half-mast

Christopher.Sorensen Thu, 09/08/2022 - 19:35

Cutline

Her Majesty Queen Elizabeth II, who died at the age of 96, was the longest-serving monarch in British history (photo by Tim Graham/Getty Images)

Rahul Kalvapalle

Topic

Global Lens

Faculty of Arts & Science

Sinai Health

Massey College

Meric Gertler

Mount Sinai Hospital

Munk School of Global Affairs & Public Policy

Queen

Royalty

St. George

Thomas Fisher Rare Book Library

UUֱ�� Libraries

UUֱ�� Mississauga

UUֱ�� Scarborough

The UUֱ�� is mourning the death of Her Majesty Queen Elizabeth II, the longest-serving monarch in British history, who visited the university on numerous occasions.

Flags on all three UUֱ�� campuses are being lowered to half-mast in memory of the Queen, who died Thursday at Balmoral Castle in Scotland at the age of 96. They will remain at half-mast until the day of her state funeral.

The university will also mark the event by having carillonists play the bells in Soldiers’ Tower on Friday at noon, tolling the largest bell once for each year of the Queen’s age at the time of her passing. The royal anthem and O Canada will also be played.

UUֱ�� President Meric Gertler said the UUֱ�� community joins all Canadians in mourning the loss of the sovereign, noting that, before acceding to the throne, she promised to devote her life to the service of her people.

“She fulfilled that promise with unparalleled grace and dignity, and in so doing set a magnificent example for us all,” President Gertler said in a statement. “Her unfailing devotion to duty has been a constant source of strength and continuity for generations of Canadians as well as countless others around the world.

“Indeed, it is difficult to imagine a world without her.”

Flags fly at half mast at, from left to right, UUֱ�� Mississauga, St. George and UUֱ�� Scarborough to mark the Queen’s death on Sept. 8, 2022 (photos by Nick Iwanyshyn, Johnny Guatto and Raquel Russell)

He also highlighted the Queen’s contributions to international peace and solidarity through the Commonwealth and noted the UUֱ�� community has been enriched by the contributions of students, faculty, librarians, staff and alumni who arrived from or live in fellow Commonwealth countries.

“In tribute to Her Majesty, in this time of sadness and in the years to come, let us remember and learn from her life of dedicated and extraordinarily generous service to others, and give thanks for a life very well lived.”

Princess Elizabeth and the Duke of Edinburgh are greeted at Hart House by UUֱ�� Chancellor Vincent Massey (Walter F. Mackenzie/UUֱ�� Archives)

The Queen’s passing comes 14 months after her husband Prince Philip, the Duke of Edinburgh, died aged 99.

Princess Elizabeth visits Hart House with UUֱ�� Chancellor Vincent Massey on Oct.13, 1951 (Walter F. Mackenzie/UUֱ�� Archives)

Prime Minister Justin Trudeau said that it is with the “heaviest of hearts” that Canadians learned of the passing of the country’s longest-reigning sovereign.

“For most Canadians, we have known no other Sovereign. Queen Elizabeth II was a constant presence in our lives. Time and again, Her Majesty marked Canada’s modern history,” he said in a statement.

Born Elizabeth Alexandra Mary on April 21, 1926, Queen Elizabeth II ascended to the crown in 1952 at age 25. She went on to become the longest-reigning monarch in British history, marking her Platinum Jubilee this past February.

She is to be succeeded as monarch by her eldest son Charles, Prince of Wales – now King Charles III.

David Onley, former lieutenant governor of Ontario and a senior lecturer in the department of political science at UUֱ�� Scarborough, said he has warm recollections of meeting the Queen at Buckingham Palace in 2008.

“The experience my wife and I had was quite amazing to us in that the conversation was not superficial. The Queen really engaged in our conversation,” Onley said.

He added that the Queen took great interest in the results of Canada’s federal election, which had taken place the night before. “I was really quite amazed as to how well-briefed she was. She wanted to know about Stephen Harper, she wanted to know about why the Liberals had lost so badly on that occasion – so it wasn’t just a superficial chit-chat.

“At the same time, I would say that she interacted with everybody like that – and that was one of the fundamental reasons for her passing being felt by so many people. Because everybody has stories – if you met the Queen, you had a story – and that was because of her degree of engagement.”

Onley said the Queen’s impeccable reputation during her seven-decade reign – he noted that her first prime minister was Winston Churchill and her last, the recently elected Elizabeth Truss; and that she had met all but one of the U.S. presidents since the Second World War – was testament to her complete devotion to the role.

“This is a particular accomplishment, and you would not have that kind of reputation if you were just effectively mailing in the responsibilities,” Onley said. “She saw it as a lifetime of service and executed that service right to the very end.”

He added that the frequency and range of the Queen’s visits to Ontario and Canada “give you the sense of the degree of interest that she had in this province, and other provinces as well.”

Queen Elizabeth II attends the Festival of Ontario at the CNE in 2002, making a stop in front of the UUֱ�� Blue Sky Solar Racing Team’s display (photo via Flickr)

Queen Elizabeth II and the Duke of Edinburgh visited Toronto seven times, with their first visit taking place in 1951, four months before the Queen’s coronation. On that occasion, the royal couple were driven to the steps of Hart House, where they waved to cheering crowds and posed for photos.

In 1973, the Queen returned to Toronto and laid the cornerstone for the new Mount Sinai Hospital, part of Sinai Health and one of UUֱ��’s partner hospitals. The hospital is located next to Princess Margaret Cancer Centre, named in honour of the Queen’s sister.

In 2002, the royal couple visited Toronto again during the Queen’s Golden Jubilee, which coincided with UUֱ��’s 175^th anniversary. During the celebrations, the Queen visited a UUֱ�� display where she spoke with undergraduate students from the Blue Sky Solar Racing team who were present with their solar-powered car.

“I recall that the Queen had such a presence,” said Nicolle Wahl, director of content in UUֱ�� Mississauga’s Office of Communications, who was present at the UUֱ�� display. “[She was] very warm and curious – and it was wonderful to see how excited the students were to meet her.”

A letter written by Princess Elizabeth to UUֱ�� Chancellor Vincent Massey dated Feb. 17, 1952 (photo by Larysa Woloszansky)

The Queen’s 22^ndand final tour of Canada took place in 2010 and included a visit to Queen’s Park – named in honour of her great-great-grandmother Queen Victoria and located amid UUֱ��’s St. George campus – where she presented Ontario Medals for Good Citizenship and waved to thousands of cheering well-wishers.

The Queen’s impact on UUֱ�� did not end with her last visit to Toronto, however. In 2017, Massey College announced that the Queen agreed to designate the college’s St. Catherine’s Chapel as the third Chapel Royal in Canada, which made it the first interdenominational Chapel Royal in the country.The request for the designation was made by John Fraser, then the master of Massey College, with the support of the Mississaugas of the New Credit First Nation. It was inspired in part by the Truth and Reconciliation Commission of Canada’s Calls to Action.

UUֱ��’s Thomas Fisher Rare Book Library has one of 25 souvenir Bibles created to mark the Queen’s coronation in 1953 (photo by Johnny Guatto)

The Queen’s ties with Massey College can be traced back to her close relationship with the college’s founder Vincent Massey, who was Canada’s 18^th Governor General and a UUֱ�� chancellor from 1947 to 1953.

Letters written by the Queen to Massey – and preserved at UUֱ��’s Thomas Fisher Rare Book Library – speak to a warm personal rapport.

In one letter dated February 1952, the Queen responded to a letter of condolence sent to her by Massey upon the passing of her father, King George VI. In her letter, the Queen expresses her gratitude for Massey’s condolences and notes that her father was in much better condition when Massey had last met him, but had then taken a turn for the worse. The Queen also states her regret at the fact that she was on a tour in Africa when her father died and was saddened by not being able to be home to comfort and console her mother and sister.

Another letter written from Balmoral Castle – where the Queen would eventually take her last breath – thanked Massey for being a great governor general. In another letter to Massey, written from Buckingham Palace in 1957, the Queen recounts her visit to the United States.

A letter written by Queen Elizabeth II to Vincent Massey on the occasion of his retirement as governor general of Canada (photo by Johnny Guatto)

The Thomas Fisher Rare Book Library is also in possession of one of 25 souvenir Bibles created to mark the Queen’s coronation in 1953. Bible #1 was used for the coronation ceremony – the Queen gifted Bible #17 to Massey.

Randall Hansen, professor in the department of political science in the Faculty of Arts & Science and the director of the global migration lab at the Munk School of Global Affairs & Public Policy, said the Queen’s many accomplishments include overseeing a modernization of the monarchy – noting as examples her decision to agree to pay income tax and the landmark wedding of Prince Harry and Meghan Markle.

“Leaving aside how it all ended, the marriage of Meghan Markle and Prince Harry was a moment of a highly modern monarchy – an inter-racial marriage and a Black Baptist American minister who oversaw the service.”

He added that the Queen’s son and heir to the throne will benefit from the prestige of the monarchy and the Queen’s impact on the institution.

“It is the institution of the Crown, it is the institution of the monarchy that bestows the prestige … that institution will bequeath on him the full prestige of the monarchy,” Hansen said. “I suspect that he’s going to be quite a successful King.”

Hansen said it was remarkable that Queen Elizabeth II, over the course of an extraordinarily long reign, was not embroiled in a scandal of any significance.

“The Queen somehow managed to be above all of that, decade after decade after decade.”

John Dick and Zulfiqar Bhutta win Canada Gairdner Awards

Christopher.Sorensen — Tue, 05 Apr 2022 13:20:56 +0000

John Dick and Zulfiqar Bhutta win Canada Gairdner Awards

Christopher.Sorensen Tue, 04/05/2022 - 09:20

Cutline

John Dick and Zulfiqar Bhutta have been honoured with 2022 Canada Gairdner Awards, the country’s most prestigious awards for medical and health science (photos courtesy of Images by Delmar and The Hospital for Sick Children)

Jim Oldfield

Topic

Dalla Lana School of Public Health

Pediatrics

Gairdner Award

Hospital for Sick Children

Molecular Genetics

Nutritional Sciences

Two researchers at the UUֱ�� and its hospital partners – one a stem cell biologist, the other a global health researcher – have been honoured with 2022 Canada Gairdner Awards, the country’s most prestigious awards for medical and health science.

John Dick was recognized with a Gairdner International Award for the discovery of leukemic stem cells and later work on the diagnosis and treatment of acute myeloid leukemia. He first received the news from Janet Rossant, president and scientific director of the Gairdner Foundation, earlier this year.

“When Janet called, it was definitely an ‘Oh my gosh’ moment,” said Dick, a professor of molecular genetics at UUֱ��’s Temerty Faculty of Medicine and a senior scientist at Princess Margaret Cancer Centre, University Health Network.

“I recall being asked to sit on an evaluation panel for the Gairdners in the early 1990s, not long after setting up my lab in Toronto. That seemed like the epitome of achievement and I never imagined in my wildest dreams that one day I’d receive a Gairdner award.”

The John Dirks Canada Gairdner Global Health Award went to Zulfiqar Bhutta for his research on community-based and policy interventions in child and maternal health, especially among vulnerable populations.

“I’m very pleased and grateful,” said Bhutta, a professor in the departments of nutritional sciences and pediatrics at Temerty Medicine and at the Dalla Lana School of Public Health, and the director of the Centre for Global Child Health and a senior scientist at The Hospital for Sick Children.

“There are not many awards for research in global or public health, and the Gairdners occupy a special place in Canada and globally,” said Bhutta, who moved to Toronto in 2013 and maintains a research group at the Aga Khan University in Pakistan. “It really is a pinnacle and most humbling.”

John Dick: Growing Toronto’s stem cell legacy

Dick and his lab were the first to discover and describe leukemia stem cells, which can self-renew and drive both cancer growth and relapse after treatment.

Those findings have led to new clinical approaches for acute myeloid leukemia and related blood cancers, and spurred research on the role of stem cells in solid tumours of the colon, breast and brain, among other sites.

Dick said he didn’t set out to discover leukemia stem cells, but instead began by “plugging away” at basic science on the blood system in mice, experimenting with ways to put genes into stem cells.

In a key advance in the late 1980s, Dick’s lab developed a way to transplant human blood stem cells into immune-deficient mice. This “xenograft assay” was a world-first and enabled Dick and other researchers to track and test the human cells’ growth and replication, albeit in the living system of the mouse.

At the same time, Dick’s lab created the first xenograft models of human leukemia and developed a method to purify leukemia stem cells, allowing for detailed comparisons of those cells and leukemia cells without stem-like properties.

“Most people thought those early experiments wouldn’t work,” said Dick. “But lo and behold some of them worked beautifully, and we were able to characterize leukemia stem cells and non-stem cells. Leukemia is a caricature of normal development and we exploited that.”

Dick and his team began counting individual cells – much like James Till and Ernest McCulloch after their discovery of stem cells in Toronto in 1961, Dick noted. They made the startling finding that stem cells are extremely rare in acute myeloid leukemia – roughly one in a million, in a given population of leukemia cells.

They later found that relapse of acute myeloid leukemia is linked to the survival of leukemia stem cells after therapy and, using patient blood samples, they showed that leukemia stem cells that cause relapse are already present in the blood the day the patient first shows up at the clinic and before therapy begins.

Dick’s lab eventually developed a 17-gene “stemness score” that physicians use to predict patient risk and outcomes, which increasingly helps guide therapeutics. “It’s a new kind of approach for effective patient-specific intervention, which is gratifying,” Dick said.

Dick credits many colleagues for his successes, starting with the trainees in his lab. He said their technical skills and passion were critical, and that their ideas were often essential.

“For most of our findings, no one had the right ideas,” Dick said. “We just threw our thoughts in a melting pot – the good and the bad, and the resulting fusion took us in completely unexpected directions. In that intellectual foment, trainees have contributed so much. They’ve been the best post-docs and graduate students you could imagine.”

He also thanked his clinical collaborators at Princess Margaret Cancer Centre and other hospitals, as well as his colleagues at UUֱ��.

“Human disease is the best sourcebook for raising and testing research questions, so I needed that constant interchange with clinicians,” Dick said. “But I benefited hugely from the intellectual rigour and collegiality of my colleagues in molecular genetics. I don’t think I could have done this work anywhere but Toronto.”

Zulfiqar Bhutta: Thinking big for the smallest and vulnerable

Bhutta’s career began in neonatology in Pakistan, but he soon expanded his focus beyond infants.

“I realized you can’t work with babies without working with mothers – and the moment you start working with mothers, you get to social determinants of health,” said Bhutta, the first UUֱ�� faculty member to win the John Dirks Canada Gairdner Global Health Award.

For more than three decades, Bhutta’s research has influenced policy and practice in global child and maternal health through implementation science, research synthesis and trials, as well as studies of malnutrition and obesity, among other approaches.

“I’ve learned as I went along, but I’ve been fortunate to work in a variety of areas, often on large-scale projects, with opportunities to make a difference in the short- and long-term,” said Bhutta, who is also affiliated with UUֱ��’s Joannah & Brian Lawson Centre for Child Nutrition.

Bhutta and his colleagues at Aga Khan University provided some of the first scientific evidence on the impact of “lady health workers” in community-based interventions in Pakistan. The government of Benazir Bhutto began employing the workers in the mid-1990s, with the goal of reducing child and maternal risk factors and deaths.

Bhutta and his team helped evaluate those interventions in a series of cluster randomized trials – a method common in public health that allows researchers to compare program impacts across groups or clusters of people. Among their findings: using chlorhexidine for cord care during home births reduced neonatal infection and death – and public-sector community health workers working in rural populations could indeed help reduce perinatal fatalities.

They also showed that when women began to visit health facilities, facility-based births increased. Moreover, they found that women’s embrace of the community health system did not falter after the formal period of the intervention ended.

“That’s diffusion of innovation, when improvements become ingrained,” said Bhutta. “People said that women would suffer de-development after the initial intervention, but that did not happen. The lesson was that when you increase capacity around women’s health, you can move away and they never look back.”

Bhutta and his team provided evidence for expansion of the community-based worker model in Pakistan and countries in the Global South, but their work also highlighted the limits of what those workers can achieve.

“You can’t do much about a woman who is bleeding to death without access to a facility with a blood bank,” Bhutta said. “I’ve seen many efforts to upgrade community interventions to physician-level care fall flat because community workers are not physicians.”

Many of those failures were closely linked to social determinants of health, Bhutta said. He recalled that in a Pakistani hospital where his wife worked in the 1990s, pregnant women kept arriving dead at the hospital despite living just a few kilometres away. It turned out the delays were often due to an imbalance in decision-making power between males in females, a lack of money for transport or misunderstanding of the severity of the medical crisis.

“These problems don’t have a biomedical solution,” said Bhutta. “They need education, women’s empowerment, and building social and economic resources at the community level.”

Today, Bhutta continues to pursue research on child and maternal health in the Global South and among marginalized populations in high-income countries. But he is broadening his focus further to address another social determinant of health: climate change.

“I would like to work on solutions to climate change for the poorest of poor before countries agree and develop policy,” said Bhutta. “People are dying now from food shortages and heat shocks. I want to help bring communities together on a self-help basis to promote innovations without the need for external supports. Watch that space.”

The Gairdner Foundation was established in 1957 to recognize research that impacts human health and has since given 402 awards to scientists around the world. About a quarter of those researchers later received Nobel Prizes. The foundation gives seven awards annually. Each recipient receives $100,000 and participates in public lectures, research symposia and other outreach events. The foundation is supported by the Government of Canada.

Gut bacteria linked to immune suppression in pancreatic cancer: Study

Christopher.Sorensen — Wed, 09 Feb 2022 17:20:25 +0000

Gut bacteria linked to immune suppression in pancreatic cancer: Study

Christopher.Sorensen Wed, 02/09/2022 - 12:20

Cutline

Tracy McGaha, a senior scientist at Princess Margaret Cancer Centre and a UUֱ�� professor of immunology, says that "in some conditions, the constituency of the microbiome may have a negative impact" on cancer outcomes (photo courtesy of Tracy McGaha)

Jim Oldfield

Topic

Breaking Research

Cancer

Immunology

Research and Innovation

Researchers at the University Health Network (UHN) and UUֱ�� have shown how probiotic bacteria in the gut could undermine immunity in pancreatic cancer, pointing toward more personalized cancer treatments.

Lactobacillus – a type of bacteria thought to promote gut health – can alter the function of immune cells called macrophages in the pancreatic tumour environment and spur cancer growth, the researchers found.

“Most studies focus on positive correlations between the microbiome and cancer outcomes,” said Tracy McGaha, a senior scientist at Princess Margaret Cancer Centre, UHN, and a professor of immunology in UUֱ��’s Temerty Faculty of Medicine. “This work focused on negative correlations of the microbiome with cancer, and suggests that in some conditions, the constituency of the microbiome may have a negative impact.”

The research was published this week in the journal Immunity.

Macrophages are tissue-resident immune cells thought to play an important role in tumour growth and metastasis. The researchers showed that Lactobacillus affects macrophage function by metabolizing dietary tryptophan, an essential amino acid found in protein from plant- and animal-based foods.

Indoles, a class of metabolites resulting from microbial tryptophan metabolization, activate the aryl hydrocarbon receptor, or AHR – a protein that regulates gene expression, and which can enable both beneficial inflammation and immune suppression in other areas of the body.

Deletion or inhibition of AHR in macrophages led to reduced growth of pancreatic cancer, better sensitivity to treatments and increased numbers of inflammatory T cells, the researchers found. The activation of AHR thwarted these beneficial effects.

McGaha said he was surprised the microbiome had such a strong impact on AHR and immune function.

“We weren’t thinking about the microbiome at first, we were just interested in AHR as a factor in the tumour microenvironment,” McGaha said. “But when we blocked the mammalian genes that can activate AHR, it had no effect.”

The researchers then looked to Lactobacillus in part because previous studies had shown that the bacteria correlated with AHR activity and reduced inflammation – both of which can enable cancer growth.

They tested the effects of the bacteria in mice with surgical models of pancreatic cancer, working in UUֱ��’s germ-free animal facility and in collaboration with Dana Philpott, who is also a professor of immunology in the Temerty Faculty of Medicine.

They also moved the project forward with single cell analysis – a technology that provides genome-scale data on individual cells, and which McGaha said was a big draw when he moved to Toronto from the U.S. in 2015.

“The technology was new then, but it’s been invaluable for us to see population responses in the gene expression patterns of macrophages and other immune cells, and what’s going on around them.”

The researchers later used tissue samples and data from human trials to show that high expression of AHR correlates with disease progression, immune suppression and patient survival.

Pancreatic cancer is notoriously difficult to treat. It is the third-most deadly cancer in Canada, despite being relatively rare, and patients with the disease have not seen the gains in survival common in other cancers over the last three decades.

To help address the urgent need for more effective treatments, McGaha is working with clinician scientists at UHN on a clinical trial called PASS-01. The study is a collaboration with other Canadian and U.S. cancer centres that aims to uncover personalized predictors of patient response to chemotherapy.

The team will collect stool samples before and after chemotherapy to look for enrichment of Lactobacillus, and whether the bacteria correlates to treatment response, patient survival and their observations on how it acts in the tumour environment.

“It’s exciting as a basic scientist to be involved in translational research, and it’s been nice to see the physician scientists interested in this work,” McGaha said.

Longer term, McGaha said his lab will pursue a deeper understanding of how immune cells interact with the microbiome. The hope is to improve on promising therapies such as fecal microbiota transplants, which have been hampered by the complexity and variety of gut bacteria – or to try a new approach.

“It could be possible to bypass the need to manipulate the microbiome, through precise targeting of the immune response to microbial metabolites,” said McGaha. “That’s a cool new direction we’d like to explore.”

The research was supported by the U.S. National Institutes of Health, the Terry Fox Research Institute, the Canada First Research Excellence Fund through UUֱ��’s Medicine by Design, the John R. Evans Leaders Fund and the Canadian Institutes of Health Research.

Researchers working on injection-free cell therapy for diabetes

Christopher.Sorensen — Fri, 17 Dec 2021 20:40:18 +0000

Researchers working on injection-free cell therapy for diabetes

Christopher.Sorensen Fri, 12/17/2021 - 15:40

Cutline

Juan Carlos Zúñiga-Pflücker and Sarah Crome are among the researchers working on generating pancreatic cells that can be transplanted to diabetes patients without being destroyed by their immune systems (photos courtesy of Medicine by Design)

Julie Crljen

Topic

Institute of Biomedical Engineering

Insulin 100

Sunnybrook Health Sciences

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 UUֱ�� 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 UUֱ��, 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 UUֱ��. “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 UUֱ�� and affiliated research institutes; UHN’s Princess Margaret Cancer Centre, Toronto General Hospital Research Institute and McEwen Stem Cell Institute; and Sunnybrook Research Institute.”

Common diabetes drug not effective against early-stage breast cancer, researchers say

Christopher.Sorensen — Wed, 08 Dec 2021 03:53:19 +0000

Common diabetes drug not effective against early-stage breast cancer, researchers say

Christopher.Sorensen Tue, 12/07/2021 - 22:53

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(Photo by andresr via Getty Images)

Amanda Ferguson

Topic

Breaking Research

Institute of Health Policy Management and Evaluation

Lunenfeld-Tanenbaum Research Institute

Breast Cancer

Cancer

Dalla Lana School of Public Health

Mount Sinai Hospital

Research and Innovation