Amanda Ferguson

Researchers look to unleash the power of stem cells to repair brain injuries

Christopher.Sorensen — Tue, 31 May 2022 14:53:57 +0000

Researchers look to unleash the power of stem cells to repair brain injuries

Christopher.Sorensen Tue, 05/31/2022 - 10:53

Cutline

Andras Nagy was the principal investigator on a study by researchers at �山ǿ�� and Sinai Health that identified a new way to control the fate of neural stem cells (photo courtesy of Sinai Health Foundation)

Amanda Ferguson

Topic

Our Community

Sinai Health

Temerty Faculty of Medicine

Research & Innovation

Stem Cells

Scientists at the University of Toronto and Sinai Health say they have identified a new way to control the fate of neural stem cells, bringing researchers one step closer to unlocking the mystery of how to repair the brain after injury or stroke.

The findings, published recently in the journal Nature Communications, outline a small set of molecules able to keep two major classes of neural stem cells from losing their ability to differentiate into critical components of a mammal’s cortex, a part of the brain that controls language and information processing.

“This discovery is an exciting extension of platform technologies developed by our lab in recent years, which make cell therapy safe and universal with off-the-shelf products to treat degenerative diseases,” said Andras Nagy, who is principal investigator on the study, a professor of obstetrics and gynaecology �山ǿ��’s Temerty Faculty of Medicine, and a senior investigator at the Lunenfeld-Tanenbaum Research Institute at Sinai Health.

GABAergic and glutamatergic neurons are two major neuronal subtypes in the mammalian forebrain, or cerebral cortex. Both classes develop from cells known as neuroepithelial progenitors and play an early and important role in brain development, but then quickly lose their ability to form other cortical cell types.

To overcome this limitation, scientists in the Nagy lab identified a set of small molecules capable of keeping the progenitor cells growing without losing their developmental potential.

Furthermore, when researchers withdrew that cocktail of molecules from the stem cells, the cells continued to differentiate into cells of the human forebrain in large numbers.

“The ability to obtain an unlimited number of forebrain-forming neural epithelium from stem cells is essential for disease modelling and toxicity testing needed in the development of new drugs,” said Nagy, who is also affiliated with �山ǿ��'s Institute of Medical Science and holds the Canada Research Chair in Stem Cells and Regeneration. “These cells could be used in cell therapies, with the potential to treat strokes and other neurological diseases.”

Balazs Varga, first author on the paper who developed cell-based therapeutic approaches over the span of a decade for the project, said that understanding the forces orchestrating brain development will help identify underlying causes of diseases, leading to new treatments.

"Our work identified one way we can control the fate of neural stem cells,” said Varga, formerly a post-doctoral researcher in the Nagy lab who is now a research associate at Wellcome Trust Medical Research Council Cambridge Stem Cell Institute. “Better understanding the behaviour of the neuroepithelial cells will provide us with ideas about how we could control progenitor cell function and brain regeneration.”

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

New drug shows promise slowing tumour growth in some hard-to-treat cancers

Christopher.Sorensen — Thu, 28 Apr 2022 15:40:28 +0000

New drug shows promise slowing tumour growth in some hard-to-treat cancers

Christopher.Sorensen Thu, 04/28/2022 - 11:40

Cutline

Daniel Durocher's lab designed a new drug with CRISPR-Cas9 gene-editing technology that blocks an enzyme essential for the survival of certain cancer cells (photo courtesy of Sinai Health)

Amanda Ferguson

Topic

Breaking Research

Sinai Health

Temerty Faculty of Medicine

Alumni

Biochemistry

Molecular Genetics

Research & Innovation

Scientists at Sinai Health and the University of Toronto say a new drug designed to block an enzyme essential for the survival of certain cancer cells shows promise in curbing tumour growth.

The preclinical findings, published this month in the journal Nature, describe a new drug designed with CRISPR-Cas9 gene-editing technology in the lab of Daniel Durocher, a senior investigator at Sinai Health’s Lunenfeld-Tanenbaum Research Institute (LTRI) and a professor of molecular genetics in �山ǿ��’s Temerty Faculty of Medicine.

The researchers identified genes that are essential for the viability of CCNE1 amplified cancer cells, which are characteristic of some hard-to-treat ovarian, endometrial and bladder cancers. They found the enzyme PKMYT1 is essential in CCNE1 amplified cells, but not in otherwise healthy cells. In collaboration with precision oncology company Repare Therapeutics, the team developed a drug called RP-6306, which blocks PKMYT1 activity and effectively kills the cancer cell.

“These cancer cells depend on the PKMYT1 enzyme to survive,” said Durocher. “Our preclinical data show enormous promise in the drug RP-6306’s ability to target these types of tumours and profoundly inhibit tumour growth.”

Currently, tumors with CCNE1 amplification have very few therapeutic options. David Gallo, a senior scientist at Repare Therapeutics, said they’ve been able to demonstrate that RP-6306 is both potent and selective for oral use in humans.

“Gynecological and other solid tumours with amplifications of CCNE1 are notoriously resistant to current standard-of-care treatments,” said Gallo, co-first author on the Nature paper. “There is a dire need to find new options for these patients.”

The work was a close collaboration between the Durocher lab and Repare Therapeutics. Durocher founded Repare Therapeutics in 2016 alongside Frank Sicheri, also a Lunenfeld-Tanenbaum Research Institute senior investigator who is a professor of molecular genetics and biochemistry at �山ǿ��.

The company is built on the concept of synthetic lethality, a process that incorporates functional genomics to discover genetic vulnerabilities to specific cancer mutations.

“This close collaboration between our group and Repare highlights how industry and academia can work together to discover new treatment options for cancer patients,” said Durocher. “It’s rare that a new target is published alongside a launched clinical trial. This speaks volumes about the innovative capacity of the LTRI and its collaborators.”

Repare Therapeutics has initiated Phase I clinical trials in patients with CCNE1 amplified solid tumours, with initial results expected in late 2022.

The research was funded by Repare Therapeutics and the Canadian Institutes of Health Research.

This story was originally published at Sinai Health.

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

Cutline

(Photo by andresr via Getty Images)

Amanda Ferguson

Topic

Breaking Research

Princess Margaret Cancer Centre

Temerty Faculty of Medicine

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

University Health Network

A widely used and inexpensive type 2 diabetes drug, once hoped to hold enormous promise in treating breast cancer, does not prevent or stop the spread of the most common forms of the disease, according to new research.

The study, which has yet to be peer-reviewed, was led by Toronto researchers and run by the Canadian Cancer Trials Group under the umbrella of the Breast International Group network. It is the largest study of its kind to date, tracking more than 3,600 breast cancer patients from across Canada, the U.S., Switzerland and the U.K.

Pamela Goodwin (photo courtesy of Sinai Health)

The randomized, double-blind trial enrolled patients who were treated with two pills a day of either placebo or the diabetes drug metformin. Overall, researchers found the addition of metformin to standard breast cancer treatments did not improve outcomes in the two most common types of breast cancer, hormone receptor-positive or negative.

“The results tell us that metformin is not effective against the most common types of breast cancer and any off-label use of this drug for the treatment of these common types of breast cancer should be stopped,” said Pamela Goodwin, a professor in the department of medicine at the University of Toronto’s Temerty Faculty of Medicine, who also is a medical oncologist at Sinai Health and a clinician scientist at the Lunenfeld-Tanenbaum Research Institute.

Goodwin presented the findings this week at the 2021 San Antonio Breast Cancer Symposium.

While metformin was found not to be effective in treating the most common forms of breast cancer, Goodwin said the trial found a potentially important result for individuals with a less common but aggressive form of the disease called HER2-positive breast cancer.

For this subtype of breast cancer, researchers found there was evidence that use of metformin for five years might lead to a reduction in deaths. HER2-positive cancer makes up about 20 per cent of all breast cancers.

“Metformin is not beneficial for use in most common breast cancers, but in the cases of HER2 positive breast cancer, our findings suggest it may be beneficial,” said Goodwin, who is also a professor in the Institute of Health Policy, Management and Evaluation at the Dalla Lana School of Public Health.

“These results need to be replicated in future research before metformin is used as a breast cancer treatment, however, it could provide an additional treatment option for HER2-positive breast cancer,” said Goodwin.

Metformin belongs to a class of drugs called biguanides, which are used to treat high blood sugar or diabetes. Previous observational and pre-clinical studies suggested metformin may also reduce the risk of development and increase survival of some cancers, including breast cancer.

It was theorized the drug may slow breast cancer growth by improving patient metabolism, notably insulin levels, leading to reduced growth of cancer cells, or that it might impact cancer cells directly.

The results have been submitted for publication. A potential next step will be to prospectively test the impact of metformin in patients with HER2-positive breast cancer in a randomized clinical trial.

The multinational trial involved a large team of scientists including Goodwin and Vuk Stambolic, a professor of medical biophysics at �山ǿ�� and at senior scientist at the Princess Margaret Cancer Centre, University Health Network.

Professors Wendy Parulekar and Bingshu Chen of Queen's University and the Canadian Cancer Trials Group were also involved with the study.

The research was funded by the Canadian Cancer Society Research Institute, National Cancer Institute (U.S.), Canadian Breast Cancer Foundation, Breast Cancer Research Foundation, Cancer Research UK, Hold’Em for Life Charity Challenge and Apotex (Canada).

Moderna gives bigger antibody boost than Pfizer in elderly: �山ǿ�� researchers

Christopher.Sorensen — Tue, 17 Aug 2021 14:28:07 +0000

Moderna gives bigger antibody boost than Pfizer in elderly: �山ǿ�� researchers

Christopher.Sorensen Tue, 08/17/2021 - 10:28

Cutline

(Photo by Michael Heim via Getty Images)

Amanda Ferguson

Topic

Breaking Research

Coronavirus

Temerty Faculty of Medicine

Dalla Lana School of Public Health

Faculty & Staff

Mount Sinai Hospital

Vaccines

Early results from a new study led by researchers from the University of Toronto and Sinai Health reveals subtle differences between the immune responses of long-term care residents receiving the Pfizer-BioNTech and Moderna vaccines.

The research, which has not yet been peer-reviewed, suggests that long-term care residents in Ontario who received the Pfizer vaccine had lower antibody responses to Alpha, Beta and Gamma variants of COVID-19 than those vaccinated with the Moderna vaccine.

The researchers did not assess the Delta variant.

“Our study does raise concerns about the response to vaccination in some residents of long-term care homes in Ontario who overall responded more weakly to vaccination,” said Anne-Claude Gingras, a professor of molecular genetics in �山ǿ��’s Temerty Faculty of Medicine and a senior scientist at the Lunenfeld-Tanenbaum Research Institute (LTI), Sinai Health.

“In this population, the Moderna vaccine permitted more residents to generate an antibody response capable of neutralizing several SARS-CoV-2 variants,” added Gingras, who led study with LTRI Senior Scientist Allison McGeer, a professor in �山ǿ��’s department of laboratory medicine and pathobiology and at the Dalla Lana School of Public Health.

The study, funded by the Government of Canada through the COVID-19 Immunity Task Force, was posted last week on medRxiv, the pre-print server for health sciences. It examined the total and neutralizing antibodies produced before and after vaccination, comparing 198 long-term care residents to 78 caregivers and long-term care staff. All vaccines were given three to four weeks apart and samples were taken 14 to 28 days after the second dose of vaccine.

It showed that the differences between resident responses to the two vaccines were more common against variants of concern. Neutralizing antibodies against the Beta variant were undetectable in nearly 38 per cent of residents vaccinated with the Pfizer vaccine, compared to 11.5 per cent of residents vaccinated with the Moderna vaccine.

When it came to the Gamma variant, 29 per cent of those vaccinated with Pfizer did not neutralize the variant, whereas only five per cent of those vaccinated with Moderna were unable to neutralize Gamma.

It is unknown how these laboratory assays compare to real-life protection from COVID-19.

The study also showed that caregivers and staff, with a median age of 47, produced more neutralizing antibodies compared to residents, whose median age was 89. This is consistent with what is known about immune responses and age.

The scientists note that they only looked at one facet of the immune response – the production of antibodies – adding residents who do not mount strong neutralizing antibody responses may still be protected by other facets of their immune system, such as their T cells.

The levels of antibody needed to protect against COVID-19 infection, severe disease or hospitalization are also unknown.

“The first two waves of the pandemic had a devastating impact on LTC home residents, staff and families,” said McGeer. “As we may face a fourth wave of the pandemic, we need to be sure that we are using all the tools we have to ensure that we protect residents and staff from further harm. This includes considering whether a third vaccine dose should be offered to residents.”

McGeer said this study is timely given recent reports of several COVID-19 outbreaks due to variants of concern in Ontario long-term care homes.

Catherine Hankins, a co-chair of the COVID-19 Immunity Task Force, said the findings were valuable.

“The question of booster strategies for vulnerable people who may not mount as strong an immune response and who have had a suboptimal reaction to two doses of mRNA vaccines is drawing lots of attention and debate,” said Hankins. “The effect of the higher antigen dose in Moderna is clearly part of the puzzle.”

Hankins added that the task force is organizing a meta-analysis of data from seven studies that they have supported in long-term care settings, and they expect to have additional insights in the near future.

In memoriam: Louis Siminovitch, the father of genetic research in Canada

Christopher.Sorensen — Thu, 08 Apr 2021 15:28:46 +0000

In memoriam: Louis Siminovitch, the father of genetic research in Canada

Christopher.Sorensen Thu, 04/08/2021 - 11:28

Cutline

Louis Siminovitch was the first chair of what is now �山ǿ��'s department of molecular genetics and the founding director of Sinai Health's Lunenfeld-Tanenbaum Research Institute (photo by Dave Chan/Sinai Health Foundation)

Amanda Ferguson

Jim Oldfield

Topic

Our Community

Temerty Faculty of Medicine

Lunenfeld-Tanenbaum Research Institute

Molecular Genetics

Mount Sinai Hospital

The University of Toronto community is remembering University Professor Louis Siminovitch, a scientific visionary who was the first chair of what is today the department of molecular genetics in the Temerty Faculty of Medicine.

Siminovitch, who was also the founding director of the Lunenfeld-Tanenbaum Research Institute (LTRI) at Sinai Health, died this week nearly one year after celebrating his 100th birthday, which took place as COVID-19 forced the world to physically distance and scientists stepped up to confront the challenge of a lethal new virus.

Many former colleagues of “Lou,” as he was affectionately known, used the occasion to highlight his many contributions, and �山ǿ�� established a catalyst trainee award in his name.

“Lou had a transformative impact on biomedical research in Canada and around the globe,” said Leah Cowen, associate vice-president, research and former chair of molecular genetics at �山ǿ��.

“He was relentless in his pursuit of research excellence, with an inspiring commitment to mentoring generations of scientists and leading scientific communities.”

As a molecular biologist and pioneer in human genetics, Siminovitch made important contributions in the fields of bacterial and animal virus genetics, human genetics and cancer research, publishing more than 200 papers.

His work helped uncover the genetic bases of muscular dystrophy and cystic fibrosis, and it laid the groundwork for genetic connections to cancer. “The better the science, the better the patient care,” Siminovitch used to say.

Siminovitch contributed to the Nobel Prize-winning work in molecular genetics of Jacques Monod and Andre Lwoff during his years at the Pasteur Institute in Paris. He was an inductee in the Canadian Medical Hall of Fame, and a Companion of the Order of Canada.

Daniel Drucker recalled that when he returned from a postdoctoral position at Harvard University in the 1980s to set up a lab in Toronto as a principal investigator, a colleague suggested he speak to Siminovitch.

“Lou didn’t know me but he was very generous of his time and he gave me valuable advice on grants and direction in research that continued for many years,” said Drucker, a professor in the department of medicine at the Temerty Faculty of Medicine and a senior investigator at LTRI.

“He was a strong, opinionated personality, and not everyone was thankful when, unsolicited, he told them what to do and when. But he was a huge force in building the modern molecular biology research ecosystem in Toronto, Canada and the world.”

Siminovitch was renowned as a mentor and researcher, but also as a scientific builder. He played key roles in establishing and developing several top research environments in Canada, including the Ontario Cancer Institute at Princess Margaret Hospital and The Hospital for Sick Children Research Institute.

At age 65, when others might have contemplated retirement, Siminovitch was at the top of his game. Mount Sinai recruited him to build an academic research institute and, as inaugural director, he attracted 25 of the globe’s most eminent scientists to the team. Thanks to his foundational efforts, LTRI is today the top-ranked biomedical research institute in Canada.

“Canadian biomedical research owes a huge debt to Lou,” said Jim Woodgett, a professor of medical biophysics at the Temerty Faculty of Medicine and former Koffler director of research at LTRI. “He instilled the importance of mentorship, of quality, and of balance – and inspired us all to fulfill our potential. His impact will live on in the many scientists and leaders he inspired.”

A giant of science, Siminovitch was also a well-rounded individual with wide-ranging interests in the arts and a deep commitment to family. The Elinore and Lou Siminovitch Prize in Theatre bears his name and that of his late wife, a highly respected playwright.

Even in his final years, Siminovitch could still be found regularly at LTRI – often in the office of his daughter, Katherine Siminovitch, professor of medicine and immunology at the Temerty Faculty of Medicine and senior investigator at LTRI.

“Lou’s leadership to the scientific and academic community changed so many careers,” said Gary Newton, president and CEO of Sinai Health. “His work shaped Canadian medicine in a very profound way and his impact can be seen every day in the halls and labs of Mount Sinai Hospital.”

Mount Sinai Hospital will mark its 100th anniversary in 2023, and the hospital’s foundation is honouring Siminovitch’s achievements through a Sinai 100 Chair in his name.

At �山ǿ��, the department of molecular genetics will offer the Dr. Lou Siminovitch Catalyst Award on a competitive basis to the best acclaimed senior PhD student (3rd year or beyond), working in the broad area of genetics who demonstrates a commitment to mentorship and the importance of mentorship in enabling their scientific career.

�山ǿ�� researchers to help form national Coronavirus Variants Rapid Response Network

Christopher.Sorensen — Mon, 29 Mar 2021 19:13:41 +0000

�山ǿ�� researchers to help form national Coronavirus Variants Rapid Response Network

Christopher.Sorensen Mon, 03/29/2021 - 15:13

Cutline

Anne-Claude Gingras, a professor in the Temerty Faculty of Medicine and senior investigator at Sinai Health, is among several Canadian researchers participating in a national network to track and test COVID-19 variants (photo by Colin Dewar/Sinai Health)

Amanda Ferguson

Topic

Our Community

Coronavirus

Temerty Faculty of Medicine

Donnelly Centre for Cellular & Biomolecular Research

University Health Network

Canadian scientists at the forefront of the fight against COVID-19 – including several at the University of Toronto – have received funding from the federal government to track and test viral variants that are now spreading rapidly across the country.

The federal government said it will establish the Coronavirus Variants Rapid Response Network through a $9 million grant from the Canadian Institutes of Health Research, part of $14.3 million in new funding for research on COVID-19 variants.

More than 30 scientists are part of the effort, which is led by Marc-André Langlois at the University of Ottawa.

“Viral variants are emerging that have multiple combinations of mutations that may have different effects on the virus’s ability to infect cells or to hide from the immune system,” said Anne-Claude Gingras, a professor of molecular genetics at �山ǿ��’s Temerty Faculty of Medicine and a senior investigator in the Lunenfeld-Tanenbaum Research Institute (LTRI) at Sinai Health who is among eight co-principal applicants on the project.

“While many of the research groups involved, including ours, were already working on characterizing variants, this new funding will enable them to do so in a more efficient manner through collaborations across the country.”

Gingras is a cancer researcher who specializes in proteomics. She pivoted her lab in the early stages of the pandemic to develop blood tests that can look for antibodies to viral proteins. She said laboratories with specialized expertise will be able to join the network and contribute to variant characterization and rapidly share the results back with the rest of the team.

The scientists hope the network will allow them to rapidly act on the emergence of new variants of concern by quickly learning the virus’s features, including the potential for re-infection.

Jennifer Gommerman, a professor of immunology at the Temerty Faculty of Medicine and co-applicant on the grant, said the goal of the network is to communicate the new information in real time to Canadian public health officials and decision-makers, as well to the broader international scientific community.

“The data generated will directly alert us to the potential threats of re-infection, increased transmissibility and pathogenicity, and vaccine resistance,” Gommerman said. “This network was designed on one critical principle: to provide scientifically-based rapid-response to the variants of concern.”

Other Temerty Faculty of Medicine scientists involved in the project include James Rini, a professor in the departments of molecular genetics and biochemistry; Jason Moffat, a professor of molecular genetics and in the Donnelly Centre for Cellular and Biomolecular Research; and Andrew Morris, a professor in the department of medicine who is also medical director of the Sinai Health-University Health Network antimicrobial stewardship program.

Jeff Wrana is also part of the new network. He is professor of molecular genetics in the Temerty Faculty of Medicine and a senior investigator at LTRI who recently used his robotics lab to create an automated, next-generation sequencing platform that can accurately screen thousands for COVID-19.

Wrana and colleagues are now using that system, called SPAR-Seq, to screen all positive samples identified in the shared clinical diagnostics lab at Sinai Health and University Health Network. The goal is to identify known and novel variants that emerge in the population and are resistant to vaccination.

The grant will allow the network to operate for one year and to create a Biobank for rapid sharing of samples and data with other biobanks across Canada in order to have a harmonized approach to fight against COVID-19.

With an eye on COVID-19 variants, �山ǿ��, Sinai Health researchers design next-gen sequencing platform

Christopher.Sorensen — Wed, 03 Mar 2021 16:26:06 +0000

With an eye on COVID-19 variants, �山ǿ��, Sinai Health researchers design next-gen sequencing platform

Christopher.Sorensen Wed, 03/03/2021 - 11:26

Cutline

An automated robotics platform designed by �山ǿ�� and Sinai Health researchers is capable of analyzing thousands of COVID-19 patient samples in a single run with a high accuracy rate (photo courtesy of Sinai Health)

Topic

Temerty Faculty of Medicine

Graduate Students

Laboratory Medicine and Pathobiology

Molecular Genetics

Mount Sinai Hospital

Research & Innovation

University Health Network

A robotics platform designed by Sinai Health and University of Toronto researchers to screen COVID-19 samples could revolutionize how labs track the spread of viruses and other pathogens.

The next-generation, ultra-high-throughput sequencing system, called C19-SPAR-Seq, has a sensitivity rate greater than 95 per cent during peak virus onset and transmissibility, and over 90 per cent in samples with a low viral load.

The researchers’ approach was detailed in a study published this week in the journal Nature Communications.

“Identifying positive samples quickly and accurately is critical in beating this pandemic,” said Jeff Wrana, a professor of molecular genetics in �山ǿ��’s Temerty Faculty of Medicine and senior investigator at Sinai Health’s Lunenfeld-Tanenbaum Research Institute (LTRI).

“With new and potentially dangerous variants now circulating, this platform is scalable, automated and capable of analyzing thousands of COVID-19 patient samples in a single instrument run.”

Wrana and colleagues are now using the system to screen all positive samples identified in the shared clinical diagnostics lab at Sinai Health and University Health Network. The goal is to identify known and novel variants that emerge in the population.

“By systematically screening all positives using C19-SPAR-Seq, we can provide rapid feedback on the frequency of known variants in the population and quantitate their expansion – and most importantly, enable early discovery of emergent variants,” Wrana said, adding that, as SARS-CoV-2 continues to evolve, it will be critical to catalogue variants that might evade immune responses in previously infected or vaccinated people.

A team of trainees shifted from other areas of research to help develop and validate the platform, allowing the group to go from concept to published paper in under 12 months.

“The system is extremely reliable and readily adaptable,” said Javier Hernandez, a doctoral student in molecular genetics at �山ǿ�� who was a co-lead author on the study with Marie-Ming Aynaud and Seda Barutcu.

“The turnaround is approximately 24 hours. It’s very simple as we’ve automated practically every step in the process,” Hernandez said. “It’s been very exciting to see my work make a difference.”

Laurence Pelletier is a professor of molecular genetics at �山ǿ�� and a senior investigator at the Lunenfeld-Tanenbaum Research Institute who was co-corresponding author on the paper with Wrana. He said the shared clinical diagnostic lab provided access to thousands of samples and was key to the study’s success.

The diagnostic lab is led by Tony Mazzulli, a professor of both medicine and laboratory medicine and pathobiology at �山ǿ��, who is microbiologist-in-chief for Sinai Health and University Health Network.

“It has been an absolute pleasure to work with Jeff and his team at the LTRI,” said Mazzulli. “His novel SPAR-Seq system is cutting-edge technology and his team’s ability to sequence COVID-19 samples in real time has tremendous potential for impacting our understanding of the epidemiology and spread of novel mutants in the province.”

The platform is also cost-effective. The study notes it only costs about US$8 per test when running thousands of samples at once, as the cost per sample decreases due to economies of scale.

This study was supported by the university’s Toronto COVID-19 Action Fund and a donation from the Krembil Foundation.

Coronavirus antibodies last at least three months after infection, �山ǿ�� study finds

Christopher.Sorensen — Thu, 08 Oct 2020 21:44:46 +0000

Coronavirus antibodies last at least three months after infection, �山ǿ�� study finds

Christopher.Sorensen Thu, 10/08/2020 - 17:44

Cutline

�山ǿ��'s Jennifer Gommerman, who led the study's saliva testing effort, says a properly designed vaccine has the potential to induce a durable antibody response to the virus that causes COVID-19 (photo by Nick Iwanyshyn)

Amanda Ferguson

Topic

Breaking Research

Coronavirus

Temerty Faculty of Medicine

Biochemistry

Graduate Students

Immunology

Laboratory Medicine and Pathobiology

Molecular Genetics

Mount Sinai Hospital

Research & Innovation

St. Michael's Hospital

Coronavirus antibodies can last at least three months after a person becomes infected with the virus that causes COVID-19, according to a study published in Science Immunology.

Researchers from the University of Toronto and the Lunenfeld-Tanenbaum Research Institute at Sinai Health used both saliva and blood samples from COVID-19 patients to measure and compare antibody levels for over three months post-symptom onset.

They found that antibodies of the IgG class that bind to the SARS-CoV-2 spike protein are detectable for at least 115 days, representing the longest time interval measured. The study is also the first to show these antibodies can also be detected in the saliva.

“Our study shows that IgG antibodies against the spike protein of the virus are relatively durable in both blood and saliva,” said Jennifer Gommerman, professor of immunology in �山ǿ��’s Temerty Faculty of Medicine and leader of the saliva testing effort.

“Our study suggests saliva may serve as an alternative for antibody testing. While saliva is not as sensitive as serum, it is easy to collect.”

The saliva assay was developed at �山ǿ�� while a team at Lunenfeld-Tanenbaum, led by senior investigator Anne-Claude Gingras, who is also a professor of molecular genetics at �山ǿ��, executed the serum assay.

“The LTRI platform for detection of antibodies in serum, or blood, is incredibly robust and well suited for assessing the prevalence of infection within the community,” said Gingras. “This is another tool that can help us better understand and even overcome this virus.”

Anne-Claude Gingras, a professor of molecular genetics at �山ǿ��, led a team at the Lunenfeld-Tanenbaum Research Institute that executed the serum assay for the study (photo courtesy of Mount Sinai Hospital)

Most people who recover from COVID-19 develop immune agents in their blood called antibodies that are specific to the virus. These antibodies are useful in indicating who has been infected, regardless of whether they had symptoms or not.

A large team of scientists collaborated on the study, including Allison McGeer and Mario Ostrowski, who provided access to the paired saliva and serum samples from dozens of patients for the study.

McGeer is a professor of laboratory medicine and pathobiology at �山ǿ��, a senior clinician scientist at Lunenfeld-Tanenbaum and principal investigator of the Toronto Invasive Bacterial Diseases Network. Ostrowski is a professor of medicine, immunology, and laboratory medicine and pathobiology at �山ǿ�� and a scientist at St. Michael’s Hospital, Unity Health Toronto.

The study was co-led by �山ǿ�� graduate students Baweleta Isho, Kento Abe, Michelle Zuo and Alainna Jamal. James Rini, a professor of biochemistry and molecular genetics at �山ǿ��, and Yves Durocher from the National Research Council of Canada, provided key protein reagents for the saliva studies.

The durability of the antibody response to SARS-CoV-2 has been debated in recent months. An earlier study published in Nature Medicine suggested the antibodies can disappear after two months for some individuals who had the virus but did not experience symptoms.

This study led by the Toronto team is in agreement with findings from leading immunologists in the U.S. in describing the antibody response as longer lasting.

While the team admits there is a lot they still don’t know about antibody responses to SARS-CoV-2 infection, including how long the antibodies last beyond this period or what protection they afford against re-infection, the research could have broader implications in the development of an effective vaccine.

“This study suggests that if a vaccine is properly designed, it has the potential to induce a durable antibody response that can help protect the vaccinated person against the virus that causes COVID-19,” Gommerman said.

The research was supported by an Ontario Together grant and funding from the Canadian Institutes of Health Research. Funding for the development of the assays in the Gingras lab was provided through donations by the Royal Bank of Canada, Questcap and the Krembil Foundation.

�山ǿ�� antibody test detects past infection, quality of immune response for COVID-19

lanthierj — Thu, 16 Jul 2020 11:51:39 +0000

�山ǿ�� antibody test detects past infection, quality of immune response for COVID-19

lanthierj Thu, 07/16/2020 - 07:51

Cutline

Professor Anne-Claude Gingras* and her colleagues designed a blood test that can detect the presence of SARS-CoV-2 antibodies and evaluate the quality of the immune response (photo by Colin Dewar/Sinai Health)

Topic

A blood test designed by researchers at the University of Toronto and Sinai Health’s Lunenfeld-Tanenbaum Research Institute can accurately detect whether a person was previously infected with the virus that causes COVID-19 – and whether their immune response is functional.

The researchers found the test can detect the presence of antibodies to the SARS-CoV-2 virus and also evaluate whether these antibodies can block attachment of the viral spike protein to the human protein ACE2, a critical step in the infection process.

“This study goes well beyond the normal detection of antibodies and provides insight into the functionality of those antibodies,” said Anne-Claude Gingras, a co-leader of the effort who is a professor of molecular genetics at �山ǿ�� and senior investigator at LTRI. “It takes a village to make important scientific advances, and this project was no different.”

The biology pre-print server bioRxiv published the study results.

Gingras and her lab worked with James Rini, a professor of biochemistry and molecular genetics at �山ǿ��, as well as the National Microbiology Lab in Winnipeg, Canadian Blood Services and the National Research Council of Canada, among others.

“Using this test, we are able to quantitate the levels of receptor-blocking antibodies found in a given patient's serum,” Rini said. “Information of this sort provides insight into how we might develop therapeutics and vaccines to combat COVID-19.”

Neutralizing antibodies hold great promise in the development of COVID-19 vaccines and other potential therapies, although that potential has not yet been realized.

Jim Woodgett, Koffler director of research at LTRI and a professor of medical biophysics at �山ǿ��, said the assay for neutralizing antibodies provides a deeper understanding of the immune response to COVID-19 infection.

“This is a bit like the difference between finding a bunch of batteries versus knowing which ones actually work,” Woodgett said. “We don’t just want to know whether a person has had a prior infection but whether they generated a degree of immunity. This is why a functional assay is much more useful than a detection test.”

However, the researchers warn that it is still unclear how long those antibodies remain functional in fighting off reinfection.

Detecting neutralizing antibodies typically involves working with live virus, a requirement which greatly limits widespread screening. This form of testing does not use live virus, but instead uses purified fragments of the viral spike protein and ACE2, which means the assay can be performed in standard immunology and clinical laboratories.

In the coming months, the team hopes to test up to 1,000 volunteers as part of the next phase of their research into a mass-scale serology test for COVID-19.

The study was supported by the Canadian Institutes of Health Research, Canada Foundation for Innovation, Royal Bank of Canada, Questcap, the Krembil Foundation, Genome Canada, Ontario Genomics, Ontario Government, and the New York State Department of Health.

* In the photo above, Professor Gingras is using the appropriate level of safety gear for the lab pictured; read more about safety gear at �山ǿ��.

Researchers at �山ǿ��, Sinai Health working on blood test to screen thousands for COVID-19 immunity

Christopher.Sorensen — Tue, 07 Apr 2020 12:53:48 +0000

Researchers at �山ǿ��, Sinai Health working on blood test to screen thousands for COVID-19 immunity

Christopher.Sorensen Tue, 04/07/2020 - 08:53

Cutline

Project co-lead Anne-Claude Gingras, a �山ǿ�� professor of molecular genetics and a senior investigator at Sinai Health, says the test is needed to monitor the percentage of the population that has been infected (photo by Colin Dewar/Sinai Health)

Amanda Ferguson

Topic

Our Community

Coronavirus

Lunenfeld-Tanenbaum Research Institute

Research & Innovation

A team of researchers at Sinai Health System and the University of Toronto is in the early stages of developing a blood test that can identify who is immune to COVID-19 on a mass scale.

The test is an adaptation of an ELISA assay (enzyme-linked immunosorbent assay) and has the potential to enable hospitals and other institutions to screen up to 10,000 samples at once, allowing entire workforces to be tested efficiently.

The blood-based test, which the team hopes to test on volunteers within the next two weeks, does not directly detect the live virus and is not intended to replace current tests for infection.

Anne-Claude Gingras, project co-lead, said the test works by detecting antibodies in the immune system of infected patients. Those antibodies persist in blood even after the virus has been completely eliminated.

“The entire city has come together to make this possible,” said Gingras, a senior investigator at Sinai Health’s Lunenfeld-Tanenbaum Research Institute (LTRI) and a professor of molecular genetics at �山ǿ��. “This test is being developed with the goal of monitoring the percentage of the population that has been infected and to help in identifying those individuals that may have protective immunity.”

The project is a collaboration between Gingras and Jeff Wrana, also a senior investigator at LTRI and a professor of molecular genetics at �山ǿ��, and other researchers from the Faculty of Medicine.

The team includes James Rini, a professor of biochemistry and molecular genetics who was key to producing proteins for the assay, and Professors Jennifer Gommerman and Mario Ostrowski from the department of immunology, who helped supply samples from pre-pandemic subjects as well as patients infected early in the pandemic who have since recovered.

The new ELISA test can provide valuable information about the spread of SARS-CoV-2 in Canada, said Karen Maxwell, an assistant professor of biochemistry who is helping to co-ordinate COVID-19 research at �山ǿ��.

“This test will allow us to track the true spread and magnitude of the disease,” Maxwell said. “Determining who has been infected and has antibodies will be important information for making decisions about how and when we return to our normal activities.”

The test will make use of the robotics platform at LTRI. Jim Woodgett, director of research at LTRI and a professor of medical biophysics at �山ǿ��, said such advances are possible thanks to close collaboration between scientists across institutions.

“Sinai Health and the University of Toronto are ideally positioned to develop this critically important antibody-based test,” Woodgett said. “This research group is eager to contribute in any way possible to help Canada overcome this historic public health challenge.”