Temerty Faculty of Medicine

Institute of Health Policy Management and Evaluation

Unity Health

Alumni

Chemistry

Dalla Lana School of Public Health

Faculty of Applied Science & Engineering

Faculty of Arts & Science

Faculty of Music

Hospital for Sick Children

Leslie Dan Faculty of Pharmacy

Order of Canada

Political Science

St. Michael's College

University College

University Health Network

Victoria College

Subheadline

"The Order of Canada recognizes individuals who have made positive and lasting impacts on communities here in Canada or who have brought honour to our country abroad"

An innovator in chemical catalyst development. A global leader in cardiac surgery and care. And a public health expert who led the rollout of Canada’s first colon cancer screening program.

These are a few members of the UUֱ�� community who were recently honoured with appointments or promotions within the Order of Canada.

The Governor General recently announced 83 new appointments to the Order of Canada, including two promotions within the Order.

They include Doug Stephan, a University Professor of chemistry in the Faculty of Arts & Science; Lee Errett, a professor in the Temerty Faculty of Medicine’s department of surgery, and Linda Rabeneck, a health executive and professor in the Temerty Faculty of Medicine and the Dalla Lana School of Public Health.

Established in 1967, the Order of Canada is one of the country’s highest honours, recognizing extraordinary contributions across all sectors of society.

“The Order of Canada recognizes individuals who have made positive and lasting impacts on communities here in Canada or who have brought honour to our country abroad,” Gov. Gen. Mary Simon said in a statement.

Here is a list of UUֱ�� faculty, alumni and supporters who were appointed to, or promoted within, the Order of Canada in the latest round of honourees.

Current and former faculty

Edward Cole, a staff nephrologist at Toronto General Hospital and professor in the Temerty Faculty of Medicine’s department of medicine, was named a Member of the Order for his dedication to advancing and delivering care to people living with kidney disease, his instrumental role in establishing a globally impactful kidney-paired donation program and his leadership as former physician-in-chief at the University Health Network.

Lee Errett, a professor in the Temerty Faculty of Medicine’s department of surgery, was appointed a Member of the Order for his transformative leadership in cardiac research and care, including his role in establishing St. Michael’s Hospital as a world-class centre for cardiac surgery, his dedication to educating future medical leaders and providing care in underserved areas worldwide.

Franklyn Griffiths, a professor emeritus and George Ignatieff Chair Emeritus of Peace and Conflict Studies in the department of political science in the Faculty of Arts & Science, was appointed a Member of the Order for his scholarship on Russian affairs which has advanced the Western world’s understanding of Soviet politics. An expert in Arctic international relations, Griffiths helped create the Arctic Council and pushed for Indigenous voices to play a central role in the council’s workings.

Beverley Johnston, an internationally renowned percussionist who is an adjunct professor in the Faculty of Music, was appointed an Officer of the Order for her work developing and promoting Canadian music to audiences around the world. Working in a male-dominated field, Johnston’s unconventional performances combine classical transcriptions, contemporary music and an element of theatre.

Daphne Maurer, a professor emeritus of psychology, neuroscience and behaviour at McMaster University who holds a status appointment at UUֱ��’s Institute of Health Policy Management and Evaluation in the Dalla Lana School of Public Health, was appointed an Officer of the Order for her research on visual and cognitive development in early childhood.

Linda Rabeneck, a gastroenterologist, health executive and professor in the Temerty Faculty of Medicine and the Dalla Lana School of Public Health, was named a Member of the Order for her leadership in colorectal cancer screening and prevention. Formerly the director of the Division of Gastroenterology at UUֱ��, she led the rollout of ColonCancerCheck, Canada’s first province-wide screening program.

Stephen Randall, who taught at UUֱ�� in 1971 to 1974, was named a Member of the Order for his academic contributions and advisory role in international relations. A professor emeritus at the University of Calgary, Randall’s expertise in myriad issues affecting the United States and Latin America, notably Colombia, has informed Canada’s foreign policy.

Bibudhendra Sarkar, senior scientist emeritus at the Research Institute of the Hospital for Sick Children and professor emeritus at UUֱ��’s department of biochemistry in the Temerty Faculty of Medicine, was named a Member of the Order for his achievements in advancing medical research in Canada and abroad. He discovered a novel treatment for patients with Menkes disease, a rare genetic condition, and led international efforts in South and Southeast Asia to address public health crises from contaminated groundwater.

Jonathan Scott Rose, a professor in the Edward S. Rogers Sr. department of electrical and computer engineering in the Faculty of Applied Science & Engineering, was named a Member of the Order for his pioneering work in architecture and software used in field-programmable gate arrays. Rose served as the chair of the department from 2004 to 2009 and received his PhD degree in electrical engineering from UUֱ�� in 1986.

Doug Stephan, a University Professor in the department of chemistry in the Faculty of Arts & Science, was named an Officer of the Order in recognition his world-leading research in inorganic and organometallic chemistry. His many achievements include discovering – and commercializing – a new class of catalysts that is now used in one of the largest chemical manufacturing facilities in the world. He also achieved global renown for founding the field of “Frustrated Lewis Pair” chemistry.

Alumni and friends

Sleight-of-hand artist David Ben, who graduated from University College in 1983, was named a Member of the Order for his four decades of dedication to the exploration, development and preservation of magic, including penning several books on the subject and co-founding the Magicana organization.

William Fox, a research fellow and adjunct professor at Trent University who earned his honours bachelor of arts and master of arts in archeology at UUֱ��, was named a Member of the Order for his distinguished contributions to Canadian archeology, his leadership in the Ontario Archaeological Society, and his steadfast advocacy for the involvement of Indigenous communities in preserving their material heritage.

Martha Friendly, who founded the Childcare Resource and Research Unit at UUֱ��’s Centre for Urban and Community Studies in the early 1980s, was appointed an Officer of the Order for her work with the now-independent non-profit and her advocacy for accessible, publicly funded early childhood education and care, and women’s equality.

Rosemary Ganley, a writer, activist, teacher and an alumna of St. Michael’s College, was named a Member of the Order for her lifelong advocacy for human rights, gender equity, and social justice, including co-founding Jamaican Self Help, an organization of Canadians working to support the development of healthy Jamaican communities.

Arnie Gelbart, a member of the Chancellors’ Circle of Benefactors, was named a Member of the Order for his decades-long leadership in independent film and television in his role as founder, executive producer and CEO of Galafilm Productions Inc.

James David Meekison, with a 45-year career spanning investment banking, cable television and private equity, was named a Member of the Order for his extensive philanthropy. The Jim Meekison and Carolyn Keystone Foundation supported UUֱ��’s Leslie Dan Faculty of Pharmacy’s efforts to launch the Discovery Pharmacy on the St. George campus.

Michael Perley, a UUֱ�� alumnus who completed a master’s degree in French language and literature, was named a Member of the Order for his lifelong dedication to tackling environmental and health challenges. He has been an advocate for tighter tobacco control laws, reducing second-hand smoke exposure and has led coalitions on acid rain and air pollution.

Dan Poenaru, a pediatric surgeon and professor at McGill University who earned two degrees at UUֱ��, was named a Member of the Order for his contributions to pediatric surgery in Africa, including establishing a surgical unit and training program in Kenya, co-founding three medical schools and leading initiatives for children's surgery globally.

Vaira Vike-Freiberga, an alumna of Victoria College and the first woman to serve as Latvia’s president, was named an honorary Officer of the Order for her work enriching Canada-Latvia relations and for reflecting Canadian values abroad.

– with files from Mariam Matti and Rahul Kalvapalle

New cancer treatment slows aggressive neuroendocrine tumours: Study

rahul.kalvapalle — Tue, 02 Jul 2024 13:45:10 +0000

New cancer treatment slows aggressive neuroendocrine tumours: Study

rahul.kalvapalle Tue, 07/02/2024 - 09:45

Cutline

Simron Singh, a medical oncologist at Sunnybrook Health Sciences Centre and associate professor in the Temerty Faculty of Medicine, led a study that found that radioligand therapy reduces the risk of advanced neuroendocrine tumour progression and death (photo by Kevin Van Paassen, Sunnybrook)

Topic

Sunnybrook Health Sciences Centre

Department of Medicine

Cancer

Subheadline

Research led by scientists at Sunnybrook Health Sciences Centre and UUֱ�� showed radioligand therapy to be an effective first-line treatment for advanced uncurable cancers

A novel approach for early cancer treatment known as radioligand therapy (RLT) has been shown to significantly reduce the risk of advanced neuroendocrine tumour progression and death, according to research led by scientists at Sunnybrook Health Sciences Centre and the UUֱ��.

Results of the multi-centre clinical trial, which were published in The Lancet, provided evidence for the first time that RLT – when applied in the early stages after a patient’s diagnosis – slowed down the progression of aggressive grade 2 and 3 neuroendocrine tumours of the gastrointestinal tract.

The treatment was shown to extend the average time of “progression-free survival” from approximately 8.5 months to 22.8 months.

“This is the first study to show the effectiveness of RLT as the ‘first-line’ treatment with advanced uncurable cancer, or any cancer,” said the study’s global principal investigator Simron Singh, a medical oncologist at Sunnybrook and associate professor in the department of medicine at UUֱ��’s Temerty Faculty of Medicine. “This trial is groundbreaking not only for patients with neuroendocrine cancers, but for all cancer patients as it has implications for the practice of cancer treatment broadly.”

Singh described RLT as a “game changer” in the treatment of cancer, which has traditionally been carried out by surgery, drugs or radiation. “While it’s technically radiation, it is given via a chemotherapy route through the blood until it reaches the precise location of the tumour,” said Singh, who is also an affiliate scientist at Sunnybrook Research Institute and co-founder of the Susan Leslie Clinic for Neuroendocrine Tumours at Sunnybrook’s Odette Cancer Centre.

RLT involves injecting radioactive isotopes – in this case, the drug Lutathera – through an IV. This method targets specific cancer cell receptors, delivering precise radiation to kill cancer cells while preserving healthy tissue.

The study evaluated the use of RLT earlier as a first-line (or “up front”) treatment for patients newly diagnosed with grade 2 or 3 advanced gastrointestinal neuroendocrine tumours. Although neuroendocrine cancer is uncommon, incidence is rising rapidly, and few treatments exist for patients. This cancer is resistant to most therapies, making it challenging to treat.

The results confirm the clinical benefit of earlier use of RLT for patients diagnosed with aggressive and life-threatening tumours, said Singh. “This is the next step in personalized targeted cancer therapy for patients, focused on more effectively killing cancer cells, while limiting the damage to surrounding healthy tissues.”

Further investigations of RLT as a therapeutic option are ongoing to evaluate overall survival and long-term safety, which will better define next steps for how this therapy will change cancer treatment world-wide.

The multi-site trial included investigators and participants from Canada, the United States, France, Germany, Italy, Netherlands, South Korea, Spain and the UK. An overview of the results was presented at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium in January 2024.

Add new author/reporter

Nadia Radovini

Researchers examine impact of psychosocial support program for teens with cancer

rahul.kalvapalle — Wed, 12 Jun 2024 14:59:44 +0000

Researchers examine impact of psychosocial support program for teens with cancer

rahul.kalvapalle Wed, 06/12/2024 - 10:59

Cutline

(photo by Vadym Petrochenko/iStock)

Rebecca Biason

Topic

Hospital for Sick Children

Lawrence S. Bloomberg Faculty of Nursing

Subheadline

The Teens4Teens virtual peer support group was launched to help strengthen connections between adolescents with cancer and tackle isolation

A virtual peer support program created at the Hospital for Sick Children (SickKids) shows significant potential in helping immunocompromised teenagers cope with the challenges of social isolation and physical distancing, positively impacting their well-being, a study finds.

The study – carried out by researchers at SickKids and the UUֱ�� and published in the journal Supportive Care in Cancer – examined the impact of a program called Teens4Teens on adolescents undergoing cancer treatment.

A weekly peer support group and patient education program, Teens4Teens was launched at SickKids in 2020 with the goal of supporting the psychosocial and physical health of adolescents with cancer.

According to the study, program participants reported a number of positive impacts that included feeling relatable and understood, conveying their emotions through art, developing coping mechanisms and discussing grief and relationships with family.

“One of the biggest takeaways for teens in our study group was the peer support component,” says the study’s first author Alicia Kilfoy, a PhD student in the Lawrence Bloomberg Faculty of Nursing. “They wanted a safe space to communicate with other teens with cancer who understood what they were going through.”

An unexpected finding was that Teens4Teens also acted as a training ground for broader skills development in realms such as peer mentorship, career planning and applying to post-secondary education opportunities.

For adolescents who are immunocompromised, physical distancing can be important in managing their risk of serious infection, but it can be an especially negative experience during some of their most formative years.

“The cancer situation for teens is very unique, in that the disease hits at a time when they are trying to develop their own sense of autonomy,” says Kilfoy’s supervisor and study co-author Lindsay Jibb, a scientist in the Child Health Evaluative Services program at SickKids and assistant professor at the Lawrence Bloomberg Faculty of Nursing. “Resources in pediatric oncology are often not tailored to this age group, and so this support program, according to our results, appears to be a step in the right direction.”

(L-R) Alicia Kilfoy, Lindsay Jibb and Chana Korenblum (supplied images)

Teens4Teens was originally designed by Chana Korenblum, a staff physician in SickKids’s division of adolescent medicine and assistant professor in the department of paediatrics in UUֱ��’s Temerty Faculty of Medicine.

It was implemented for young cancer patients during the COVID-19 pandemic, with the aim of providing teens with a space to connect through virtual sessions with speakers who engaged them on an array of topics related to cancer and also generally on navigating life as a teen.

Sessions were moderated by child life specialists and included guest speakers from various disciplines including nursing and creative art therapy. Each group was involved in addressing coping strategies for grief and navigating difficult feelings using activities such as music and art therapy.

“Teens told us they valued having a space where all thoughts and feelings about cancer were welcome, where they could share their stories and swap coping strategies without judgment – and most importantly, where they felt a strong sense of belonging and connectedness,” says Korenblum.

One of the big draws for teens to participate in the program was the desire to regain a sense of control. Many participants in the study reported challenges associated with feeling excluded from decision-making in their own lives – including around their medical treatment – and the negative impact of cancer on their sense of self and relationships with others.

“We also saw teens reporting that the program normalized their cancer experience in a developmentally appropriate way, and changed the way health providers were engaging with them as patients,” says Jibb, who also holds the Signy Hildur Eaton Chair in Paediatric Nursing Research at SickKids.

The study also delved into participants’ suggestions for improvement, which included making the program hybrid to provide more opportunities for in-person social connection. The researchers say the teens’ feedback will help them fine-tune and augment the program to increase recruitment, engagement and impact.

The study comes amid a growing recognition within the oncology field of the need for teen-centred programming, with Teens4Teens showing promise as a low-cost, feasible intervention.

“Adolescence can be tricky to navigate, and a cancer diagnosis can add many bumps to the road,” says Jibb. “I’m excited to see how this program continues to grow in support of teens with cancer.”

Study by UUֱ��, international researchers predicts worsening dengue spread in Mexico and Brazil

Christopher.Sorensen — Mon, 10 Jun 2024 15:11:55 +0000

Study by UUֱ��, international researchers predicts worsening dengue spread in Mexico and Brazil

Christopher.Sorensen Mon, 06/10/2024 - 11:11

Cutline

Patients await treatment at an emergency medical care unit for dengue in Brasilia, Brazil (photo by Mateus Bonomi/Anadolu via Getty Images)

Gabrielle Giroday

Topic

Department of Medicine

Global

Subheadline

Geospatial machine learning models projected “a more extensive and rapid expansion” of the viral infection than previously thought

Brazil and Mexico may be affected by a much greater spread of dengue in the years to come, according to a new study from the UUֱ��’s Temerty Faculty of Medicine.

The research, published in Nature Communications, used geospatial machine learning models to map out the future spread of dengue in the two countries until 2039 using data related to regional environmental factors as well as historical data on human population mobility.

The model predicted that the percentage of municipalities affected by dengue will rise from 76 to 97 per cent in Brazil and from 55 to 91 per cent in Mexico, which the study notes is “a more extensive and rapid expansion” than previously thought.

“COVID-19 has brought emerging infectious diseases to the forefront of public discussion. The pandemic is a reminder of the profound harm emerging infectious diseases have on health systems,” says the study’s first author Vinyas Harish, an MD/PhD student at Temerty, post-graduate affiliate at the Vector Institute for Artificial Intelligence and clinical clerk at Unity Health Toronto.

Dengue is a viral infection, spread to humans by mosquitoes, that affects 100 to 400 million people each year in tropical and subtropical climates.

While some people experience mild symptoms, for others, dengue can lead to much more serious outcomes like hospitalization or death. No specific treatment for dengue exists, says the World Health Organization, and there was a global spike in cases in 2023 which led to international concern about the surging numbers.

(L-R) Vinyas Harish, Kamran Khan and Isaac Bogoch (supplied images)

For the study, researchers – who included Professor Kamran Khan and Associate Professor Isaac Bogoch from Temerty’s department of medicine – developed and validated their models by looking at more than 8,000 municipalities in Brazil and Mexico over 25 years. They also integrated insights from historical outbreak records, climate change projections and evolutionary history of viral genetic sequences.

The researchers say they believe it’s the first time, to their knowledge, “that spatial models of disease spread have informed origins, pathways and future projections of an emerging infectious disease.”

The paper – led by Oliver Brady of the London School of Hygiene and Tropical Medicine – involved researchers from Canada, the United States, Australia, England, Brazil and Mexico.

Researchers say they hope the findings of the paper help with understanding other emerging infectious diseases, and the best ways of combatting spread of dengue in future.

What Now? AI, Episode 5: This Is Not Real

mattimar — Thu, 23 May 2024 19:33:08 +0000

What Now? AI, Episode 5: This Is Not Real mattimar Thu, 05/23/2024 - 15:33

Topic

Our Community

Schwartz Reisman Institute for Technology and Society

What Now? AI

Munk School of Global Affairs & Public Policy

Artificial Intelligence

Faculty of Arts & Science

Faculty of Information

Political Science

UUֱ�� Mississauga

Artificial intelligence presents new opportunities to strengthen democracy even as it threatens to cast a shadow over election integrity and further the spread of misinformation.

In the fifth episode of What Now? AI, UUֱ�� hosts Beth Coleman and Rahul Krishnan are joined by experts Harper Reed and Peter Loewen, who is also from UUֱ��, to explore the impact of AI on the political realm.

Listen to episode five on Apple, Spotify, SoundCloud, iHeartRadio and Amazon. Watch episode five on YouTube.

Loewen, director of UUֱ��’s Munk School of Global Affairs & Public Policy and a professor in the department of political science in the Faculty of Arts & Science, explains how AI removes the human touch from politics, potentially making the public uneasy.

“We still don't like the fact that it might be a machine that we're talking to,” said Loewen, who is also the associate director of the Schwartz Reisman Institute for Technology and Society.

“But then if you layer on this dimension of not knowing if this is actually the campaign that’s doing it, I think that’s probably orders of magnitude worse because what it does is it takes us from the realm of kind of feeling uneasy about something into feeling like this thing is corrupted.”

Reed, meanwhile, spoke about his experience as the chief technology officer on former U.S. president Barack Obama’s re-election campaign in 2012.

“The technology we built was not about convincing someone at the time that Mitt Romney was a bad person or a good person,” said Reed during a conversation with Coleman about AI and democracy that was filmed live at the Schwartz Reisman Institute for Technology and Society’s annual conference Absolutely Interdisciplinary, a portion of which was used in the podcast episode.

“The tech was more about making sure you got to vote.”

When asked about the biggest threats to AI and democracy, Reed emphasized that he is less worried about the technology itself and more with ensuring it’s beneficial to societal use.

“I’m worried about who has access to it and how they are using it.”

About the hosts:

Beth Coleman is an associate professor at UUֱ�� Mississauga’s Institute of Communication, Culture, Information and Technology and the Faculty of Information. She is also a research lead on AI policy and praxis at the Schwartz Reisman Institute for Technology and Society. Coleman authored Reality Was Whatever Happened: Octavia Butler AI and Other Possible Worlds using art and generative AI.

Rahul Krishnan is an assistant professor in UUֱ��’s department of computer science in the Faculty of Arts & Science and department of laboratory medicine and pathobiology in the Temerty Faculty of Medicine. He is a Canada CIFAR Chair at the Vector Institute, a faculty affiliate at the Schwartz Reisman Institute for Technology and Society and a faculty member at the Temerty Centre for AI Research and Education in Medicine (T-CAIREM).

Note: The artwork in the background of Peter Loewen’s interview belong to the Mirvish Family’s private collection. The large image, titled Floating Free, is by K.M. Graham. The smaller image is untitled and by the same artist.

Hospitals with higher ratio of female surgeons, anaesthetists have better patient outcomes: Study

Christopher.Sorensen — Wed, 22 May 2024 14:48:30 +0000

Hospitals with higher ratio of female surgeons, anaesthetists have better patient outcomes: Study

Christopher.Sorensen Wed, 05/22/2024 - 10:48

Cutline

Reaching a critical mass of more than 35 per cent female anesthesiologists and surgeons was linked to lower odds of severe post-operative complications, according to a study from ICES, Sunnybrook Research Institute and UUֱ�� (photo by Shannon Fagan/Getty Images)

Misty Pratt

Topic

Sunnybrook Health Sciences Centre

University Health Network

Subheadline

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

UUֱ�� researchers lead discovery of natural compounds that selectively kill parasites

rahul.kalvapalle — Tue, 21 May 2024 17:46:46 +0000

UUֱ�� researchers lead discovery of natural compounds that selectively kill parasites

rahul.kalvapalle Tue, 05/21/2024 - 13:46

Cutline

An international study led by PhD student Taylor Davie (L) and Professor Andrew Fraser (R) of the Donnelly Centre for Cellular and Biomolecular Research could have important implications for treatment of lethal parasitic worms (supplied images)

Anika Hazra

Topic

Donnelly Centre for Cellular & Biomolecular Research

Molecular Genetics

Subheadline

The compounds stall a unique metabolic process that parasitic worms use to survive in the human gut

An international team led by researchers at the UUֱ�� has found a family of natural compounds that could potentially be harnessed as treatments for parasitic worms, which wreak havoc in developing countries in the tropics.

Infection by these parasites, which are transmitted through soil, leads to malaise, weakness, malnutrition and other debilitating symptoms, and can cause developmental defects and growth impairments in children.

The newly discovered compounds stall the unique metabolic process that the worms use to survive in the human gut, according to the study, which was published in Nature Communications.

“Soil-transmitted parasitic worms infect over one billion people around the world, typically in low-income communities of developing countries without comprehensive health care and infrastructure for sanitation,” said Taylor Davie, first author on the study and a PhD student at UUֱ��’s Donnelly Centre for Cellular and Biomolecular Research. “Parasites are becoming less susceptible to the few anthelmintic drugs available, so there’s an urgent need to find new compounds.”

Many parasitic worm species spend a large portion of their life cycle inside a human host. To adapt to the environmental conditions of the gut, particularly a lack of oxygen, the parasite switches to a type of metabolism that depends on a molecule called rhodoquinone (RQ).

The parasite can survive inside its human host for many months using RQ-dependent metabolism.

The research team chose to target the adaptive metabolic process of the parasitic worm because RQ is only present in the parasite’s system – humans do not produce or use RQ. Therefore, compounds that can regulate the molecule’s production or activity would selectively kill the parasite, with no harm done to the human host.

The researchers conducted a screen of natural compounds isolated from plants, fungi and bacteria on the model organism C. elegans. Although C. elegans is not a parasite, this worm also depends on RQ for metabolism when oxygen is not available.

“This is the first time that we have been able to screen for drugs that specifically target the unusual metabolism of these parasites,” said Andrew Fraser, principal investigator on the study and professor of molecular genetics at the Donnelly Centre and the Temerty Faculty of Medicine.

“The screen was only possible because of recent progress made by our group and others in using C. elegans to study RQ-dependent metabolism, and our collaboration with RIKEN, one of Japan’s biggest research agencies.

“We screened their world-class collection of 25,000 natural compounds, resulting in our discovery of a family of benzimidazole compounds that kills worms relying on this type of metabolism.”

The researchers suggest a multi-dose regimen using the newly discovered family of compounds to treat parasitic worms. While a single-dose treatment is easier to facilitate in mass drug administration programs, a longer treatment program would eliminate the parasite more effectively.

“We are very pleased with the results of the study, which made use of our library,” said Hiroyuki Osada, professor of pharmacy at the University of Shizuoka and group director of the Chemical Biology Research Group at the RIKEN Center for Sustainable Resource Science.

“The study shows the power of the screening approach, allowing researchers in this case to search through a very large number of molecules within a focused collection of natural products. Screens are very efficient, which is key for addressing urgent research questions of global relevance like this one.”

Next steps for the research team are to refine the new class of inhibitors through additional in-vivo testing with parasitic worms, which will be performed by the Keiser lab at the University of Basel in Switzerland, and to continue screening for compounds that inhibit RQ.

“This study is just the beginning,” said Fraser. “We have found several other very powerful compounds that affect this metabolism including, for the first time, a compound that blocks the ability of the worms to make RQ.

“We hope our screens will deliver drugs to treat major pathogens around the world.”

This research was supported by the Canadian Institutes of Health Research and the European Molecular Biology Organization.

A master neuron controls movement in worms, with implications for human disease: Study

Christopher.Sorensen — Thu, 16 May 2024 15:01:59 +0000

A master neuron controls movement in worms, with implications for human disease: Study

Christopher.Sorensen Thu, 05/16/2024 - 11:01

Cutline

Researchers at the Lunenfeld-Tanenbaum Research Institute have revealed the crucial role of a neuron called AVA in controlling the worm C. elegans’s ability to shift between forward and backward motion ( photo by ZEISS Microscopy from Germany)

Jovana Drinjakovic

Topic

Sinai Health

Faculty of Arts & Science

Cell and Systems Biology

Molecular Genetics

Subheadline

The discovery offers a major new insight into a neural circuit that scientists have studied since the inception of modern genetics.

Researchers at Sinai Health and the UUֱ�� have uncovered a mechanism in the nervous system of the tiny roundworm C. elegans that could have significant implications for treating human diseases and advancing robotics.

The study, led by Mei Zhen and colleagues at the Lunenfeld-Tanenbaum Research Institute, was published in the journal Science Advances and reveals the crucial role of a specific neuron called AVA in controlling the worm’s ability to shift between forward and backward motion.

Crawling towards food sources and swiftly reversing from danger is a matter of life and death for the worms. This type of behaviour, where two actions are mutually exclusive, is common in many animals including humans – we cannot sit and run at the same time, for example.

Scientists long believed that control of movements in worms was due to straightforward reciprocal actions between two neurons: AVA and AVB. The former was thought to promote backward motion while AVB facilitated forward motion, with each neuron inhibiting the other to control movement direction.

However, the new data from Zhen’s team challenge this notion, uncovering a more complex interaction where the AVA neuron plays a dual role. It not only instantly stops forward motion by inhibiting AVB, but also maintains a longer-term stimulation of AVB to ensure a smooth transition back to forward movement.

The discovery highlights the AVA neuron’s ability to finely control movement through distinct mechanisms, depending on different signals and across different time scales.

“In terms of engineering, this is a very economical design,” said Zhen, who is also a professor of molecular genetics in UUֱ��’s Temerty Faculty of Medicine. “The strong, robust inhibition of the backward circuit allows the animals to respond to bad environments and escape. At the same time, the controller neuron continues to put in constitutive gas into the forward circuit to generate movement towards safer places.”

Jun Meng, a former PhD student in the Zhen lab who led the research, said understanding how animals transition between such opposing motor states is crucial for insights into how animals move as well as neurological disorder research – and that the worms provide a unique window into basic neural wiring that's to their simple, see-through bodies.

The discovery that the AVA neuron plays such a dominant role offers a major new insight into the neural circuit that scientists have studied since the inception of modern genetics over half a century ago. The Zhen lab successfully leveraged cutting-edge technology to precisely modulate the activity of individual neurons and record data from living worms in motion.

Zhen, who is also a professor of cell and systems biology at UUֱ��’s Faculty of Arts & Science, emphasizes the importance of interdisciplinary collaboration in this research. Meng performed key experiments, while neuronal electrical recordings were conducted by Bin Yu, a PhD student in Shangbang Gao’s lab at Huazhong University of Science and Technology in China.

Tosif Ahamed, a former post-doctoral researcher in the Zhen lab and now a Theory Fellow at the HHMI Janelia Research Campus in the United States, led mathematical modelling efforts that were crucial for testing hypotheses and gaining the new insights.

The findings provide a simplified model to study how neurons can manage multiple roles in movement control – a concept that might extend to human neurological conditions.

For example, AVA’s dual role depends on its electric potential, which is regulated by ion channels on its surface. Zhen is already exploring how similar mechanisms could be involved in a rare condition known as CLIFAHDD syndrome, caused by mutations in similar ion channels. Additionally, the new findings could inform the development of more adaptable and efficient robotic systems capable of complex movements.

“From the origin of modern science to the forefront of today’s research, model organisms like C. elegans have been instrumental in peeling back the layers of complexity in our biological systems," said Anne-Claude Gingras, director of the Lunenfeld-Tanenbaum Research Institute, vice-president of research at Sinai Health and a professor of molecular genetics in UUֱ��’s Temerity Faculty of Medicine.

“This research is a great example of how much we can learn from simple animals, to then think about applying this new knowledge to advancing medicine and technology.”

The research was supported by the Canadian Institute of Health Research, the Natural Sciences and Engineering Research Council of Canada, the National Natural Science Foundation of China and the European Research Council.

UUֱ�� researchers' approach to producing neural cells could yield new treatments for Parkinson’s

rahul.kalvapalle — Mon, 13 May 2024 13:03:19 +0000

UUֱ�� researchers' approach to producing neural cells could yield new treatments for Parkinson’s

rahul.kalvapalle Mon, 05/13/2024 - 09:03

Cutline

PhD Student Andy Yang, left, and Professor Stephane Angers, right, at the Donnelly Centre for Cellular and Molecular Biology are advancing a novel approach to developing dopaminergic neurons (supplied images)

Anika Hazra

Topic

Institutional Strategic Initiatives

Donnelly Centre for Cellular & Biomolecular Research

Graduate Students

Leslie Dan Faculty of Pharmacy

Medicine by Design

Parkinson's