Regenerative Medicine

Researchers accelerate development of cellular therapies for damaged tissues

siddiq22 — Tue, 25 Jul 2023 16:17:02 +0000

Researchers accelerate development of cellular therapies for damaged tissues

siddiq22 Tue, 07/25/2023 - 12:17

Cutline

From left: PhD candidate Oreoluwa Kolade, Professor Julie Audet and Assistant Professor Sowmya Viswanathan are working to identify the optimal cell culture conditions for different donors without doing full sets of detailed experiments (photo by Safa Jinje)

Safa Jinje

Topic

Breaking Research

Data Sciences Institute

Institute of Biomedical Engineering

Temerty Faculty of Medicine

Faculty of Applied Science & Engineering

Graduate Students

machine learning

Regenerative Medicine

Research & Innovation

Subheadline

Optimizing conditions to culture therapeutic cells can help reduce the costs and labour of experiments

Innovations in the ways that human cells are grown in laboratories could help speed up the development of cellular therapy, a branch of regenerative medicine that targets diseases that are currently incurable.

Julie Audet, a professor in the ��߲ݴ�ý's Institute of Biomedical Engineering in the Faculty of Applied Science & Engineering, is working to address some of the most significant challenges related to producing therapeutic cells.

Her research on cell and tissue engineering aims to enhance the therapeutic properties of lab-grown human cells to ensure that they are ready for clinical application.

Audet and her team are developing complex computational algorithms to optimize laboratory experiments for academic and industrial researchers. These tools will allow researchers to create the best conditions to culture therapeutic cells.

Cellular therapy acts by transplanting enhanced human cells into the body to replace or repair damaged tissue and cells, in order to treat a variety of diseases and conditions – an approach sometimes referred to as a living drug.

“But before cells can be transplanted into a patient, we want to ensure that the cells are not contaminated with compounds that can trigger an adverse reaction,” Audet says.

“We also need to enhance the therapeutic properties of the cells in a culture process to effect a positive medical outcome.”

There are many factors to consider when designing cell-culture experiments. For example, there are numerous expensive reagents to select and optimize at different doses – these substances are used to test chemical reactions carried out by the cell. There are also significant technical and biological variations to consider – cells from different donors don’t always behave the same way in culture.

“Our algorithms become necessary when experiments are very costly to execute and are extremely labour-intensive,” Audet says.

“They are especially useful when the results are impossible to predict because of the complexity of the biological systems under study. In that case, it would not be feasible or possible for researchers to use conventional approaches to design and execute their experiments.”

With complex computational algorithms based on machine learning, Audet and her team can design experiments that are not only feasible and offer a greater chance of success, but are also less costly, with fewer resources needed to execute the experiment.

An earlier prototype of such algorithms was used by Audet’s lab to make a serum-free T-cell medium to treat blood disorders. The algorithm was also used by Craig Simmons, a professor in the Institute of Biomedical Engineering and the department of mechanical and industrial engineering in the Faculty of Applied Science & Engineering, and Neal Callaghan, a PhD graduate from the institute and a former researcher in Simmons' lab, to develop culture media for cardiomyocytes (cardiac muscle cells), a process that is now being commercialized.

“Cardiac tissue engineering is an important application for our tools because when it comes to heart failure and heart disease, there are many conditions that can’t currently be cured,” Audet says.

“Cellular therapy offers a promising approach to treat heart failure and other cardiac ailments.” 

Audet is working with Sowmya Viswanathan, a researcher at the University Health Network's Krembil Research Institute and an assistant professor in the Institute of Biomedical Engineering and the Temerty Faculty of Medicine, on research that addresses the distinct characteristics of cell donors that make cells behave differently in culture.

Viswanathan is developing cellular therapies using mesenchymal stromal cells to combat osteoarthritis, a chronic inflammatory disease.

“We have seen that different mesenchymal stromal cell donors prefer different growth conditions,” Viswanathan says. “This algorithm helps us identify optimal conditions for different donors without doing a full set of detailed experiments.”

The goal of her collaboration with Audet is to also develop categories of conditions that could be matched to diverse groups of donors based on genetic markers. 

Audet and Viswanathan co-supervise Oreoluwa Kolade, a PhD candidate at the Institute of Biomedical Engineering and a fellow at the Data Sciences Institute – one of several U of T institutional strategic initiatives – whose work brings together tissue engineering and data science.

“My research involves the statistical design of experiments, looking at the numerous factors that can impact the cell expansion process, such as oxygen levels, cell density and medium composition,” Kolade says.

“If a researcher wants to see which factors maximize the therapeutic quality of their cells, it isn’t cost-effective to test all possible combinations. So we are trying to design experiments in such a way that researchers can get the highest impact when they see their results.”

This model would allow researchers to narrow down the varying factors and run combinations into a simulation model to see which experiments they would need to do to get the best cells.

“We are currently working on the commercialization of the latest version of one of the algorithms that includes these machine-learning modules to help design experiments,” Audet says.

“We hope this tool will help make cellular therapies both widely available and more accessible by accelerating the development of these therapies while increasing the effectiveness of the enhanced cells.”

U of T researchers develop antibody drug that could treat diabetic retinopathy

Christopher.Sorensen — Wed, 09 Jun 2021 16:57:27 +0000

U of T researchers develop antibody drug that could treat diabetic retinopathy

Christopher.Sorensen Wed, 06/09/2021 - 12:57

Cutline

A team led by U of T researcher Stéphane Angers has developed a synthetic antibody as a promising treatment for diabetic retinopathy, which causes blindness and affects about one third of diabetes patients (photo by Tetra Images via Getty Images)

Eileen Hoftyzer

Topic

Breaking Research

Insulin 100

Donnelly Centre for Cellular & Biomolecular Research

Leslie Dan Faculty of Pharmacy

Regenerative Medicine

Research & Innovation

The life-saving diabetic medication insulin, developed at the ��߲ݴ�ý 100 years ago, was the first biologic therapy – a protein to treat disease. Now, a new biologic therapy developed by U of T researchers has potential to reverse a common diabetes complication.

A team led by Stéphane Angers, professor and associate dean of research at the Leslie Dan Faculty of Pharmacy, has developed a synthetic antibody as a promising treatment for diabetic retinopathy, which causes blindness and affects about 30 per cent of diabetes patients.

The researchers tested the antibody in both cell cultures and mice. The results were published this week in the journal EMBO Molecular Medicine.

“This study has shown that these antibodies are very attractive therapeutics to restore blood-retina barrier defects,” said Rony Chidiac, a post-doctoral researcher in the Angers lab and lead author of the study.

“It gives new hope for the treatment of eye diseases like diabetic retinopathy and macular degeneration.”

Angers and his team are experts in the Wnt cell signalling pathway, which is crucial for the formation and maintenance of the blood-retina barrier, a physiological barrier that prevents molecules from entering the retina.

When the signalling pathway is disrupted – which can occur because of genetic mutations in rare eye conditions such as Norrie disease, or when tissue oxygen is low, as in diabetic retinopathy – the blood vessels can become leaky, causing damage in the eye.

Professor Stéphane Angers (right) works alongside post-doctoral researcher Rony Chidiac in this 2018 photo (photo by Steve Southon)

In previous research, Angers had collaborated with Sachdev Sidhu at the Donnelly Centre for Cellular and Biomolecular Research to develop a catalogue of synthetic antibodies that could activate Wnt signalling.

Their new publication describes how one of the antibodies, specifically activating the Frizzled4-LRP5 receptor complex, successfully stimulated Wnt signalling in the blood-retina barrier and effectively restored barrier function.

The antibody attaches to two key cell surface receptors (Frizzled4 and LRP5) bringing them close together, and this induced proximity activates the Wnt pathway that maintains the blood vessels.

The team first tested the antibody in cell cultures and found that it was a highly precise way to trigger the signalling pathway and restore barrier function. They then tested the antibody in different mouse models in collaboration with Harald Junge at the University of Minnesota and AntlerA Therapeutics, a start-up company founded by Angers and Sidhu. One model represented a genetic eye condition and one represented diabetic retinopathy.

Remarkably, the antibody restored the barrier function and corrected retinal blood vessel formation in mice. In addition, it normalized the pathological formation of new blood vessels, one of the consequences of a leaky blood-retina barrier that causes further eye damage.

With the antibody’s promising preclinical results, AntlerA Therapeutics will now lead the commercialization and translation to clinical studies.

While the current study’s results are focused on eye conditions, the similarities between the blood-retina barrier and blood-brain barrier mean that its applications could be much broader than eye conditions.

“The retinal vasculature was the first indication, and we have new funding to explore the role of this pathway in other contexts,” said Angers. “For example, we are testing whether this antibody could have implications in the blood-brain barrier and whether it could repair the barrier in the context of stroke.”

“We’ve found a way to activate Wnt signalling very precisely in order to have a viable therapeutic opportunity and actually treat these diseases,” added Chidiac. “We anticipate that this could have enormous impact in diverse applications in regenerative medicine.”

The research was supported by the Canadian Institutes of Health Research and the government of Ontario, among others.

U of T researchers reach across fields to stop a silent, killer disease

Christopher.Sorensen — Wed, 17 Feb 2021 14:19:57 +0000

U of T researchers reach across fields to stop a silent, killer disease

Christopher.Sorensen Wed, 02/17/2021 - 09:19

Cutline

Omar Khan and Clinton Robbins are part of a multi-disciplinary Medicine by Design research team at U of T that's focused on preventing deadly abdominal aortic aneurysms (photo supplied and by John Hryniuk)

Paul Fraumeni

Topic

Breaking Research

Institute of Biomedical Engineering

Temerty Faculty of Medicine

Faculty of Applied Science & Engineering

Immunology

Laboratory Medicine and Pathobiology

Medicine by Design

Regenerative Medicine

Research & Innovation

University Health Network

Abdominal aortic aneurysms kill people by sneak attack.

In most cases, they develop without you knowing it. There are usually no symptoms. And if they burst, only 30 per cent of victims survive. Even if they are discovered before rupturing – because of medical imaging done to investigate another condition – it usually means emergency surgery.

But what if these aneurysms could be prevented using a branch of regenerative medicine that focuses on stopping disease processes before they do their damage?

That is a question ��߲ݴ�ý researchers Clinton Robbins, Myron Cybulsky and Jason Fish are investigating. Robbins is an associate professor in the department of laboratory medicine and pathobiology (LMP) and the department of immunology in the Temerty Faculty of Medicine. He is also the Peter Munk Chair in Aortic Disease Research at the University Health Network (UHN). Cybulsky and Fish are senior scientists at the Toronto General Hospital Research Institute at UHN and faculty members in LMP. Cybulsky is Canada Research Chair in Arterial Wall Biology and Fish is Canada Research Chair in Cell and Molecular Biology.

The multi-disciplinary team is one of 11 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 support transformative discoveries in regenerative medicine and accelerate them toward clinical impact.

An aneurysm is a swelling in an artery. An abdominal aortic aneurysm, or AAA, occurs in the aorta, the largest blood vessel in the human body. It runs from the heart down through the chest and abdomen, supplying blood to the body. When there is a weakening of the walls of the aorta in the abdomen, the aorta will balloon out. That’s the aneurysm. It’s not a problem until it bursts. If that happens, it can cause life-threatening internal bleeding or blood clots that can block the flow of blood.

“The reality is that we don’t know why these aneurysms develop,” Robbins says. “We have no understanding as to why the tissue in the aorta weakens and we know less about how we might go about repairing that.”

But Robbins and his lab have made an important step forward in learning that cells called monocytes and macrophages play an important role in the progression of AAA.

Monocytes are born in the bone marrow, a spongy tissue inside some of your bones. They are white blood cells and travel throughout the body, fighting infection. They eventually turn into macrophages, which perform the same function as monocytes.

While monocytes play that positive role in the immune response, they also have a negative side – they can gather at certain sites and cause an AAA, which is a type of inflammation.

No one is quite sure why this happens, but it is known that certain risk factors promote AAAs. Men over 65 are more likely to have an AAA, for example. And cigarette smoking seems to be a common cause. In fact, Robbins has found through experiments that exposing mice to cigarette smoke drives the formation of AAA.

Robbins has also begun to wonder if the endothelium – the cells that line the blood vessels – “speak” to the monocytes and macrophages. He has observed that when the AAA develops, there is a buildup of macrophages at that inflammation site. Could this cross-talk between these cell types influence the development of the AAA?

And Robbins has another idea – shift the focus away from why monocytes gather to create an AAA and instead focus on preventing their excessive generation or stopping their entry into the bloodstream from their birthplace in bone marrow.

Enter Omar Khan, whose expertise in nanotechnology is becoming an important part of the solution Robbins and his collaborators are exploring.

“My collaborators and I have been able to model this disease in mice,” Robbins says. “But to accomplish this notion of blocking monocyte production and release, we need someone with experience in nanotechnology. That’s why I was glad when Omar joined Medicine by Design and approached me.”

Khan is an assistant professor in the department of immunology in the Temerty Faculty of Medicine and U of T’s Institute of Biomedical Engineering in the Faculty of Applied Science & Engineering. He obtained his doctorate in chemical engineering and applied chemistry at U of T in 2010 (under the supervision of Medicine by Design executive director University Professor Michael Sefton) and then moved to the Massachusetts Institute of Technology (MIT) for post-doctoral work. His research was spun out into two start-up companies, one of which he founded.

Khan returned to U of T in early 2020, becoming one of 14 new faculty members Medicine by Design has helped recruit. He’s working with nanomaterials – small chemical materials that co-ordinate the delivery of nucleic acids, which are information-carrying molecules in cells that silence, regulate, express or help edit genes. Khan’s lab is applying nanotechnologies to the treatment of chronic inflammation, autoimmune diseases, cancer immunotherapy and the clearance of viruses in incurable infections. In one of his research areas, he controls chronic inflammation by simultaneously preventing excessive monocyte generation in the bone marrow and their exit into the blood. That focus on inflammation is the connection to Robbins’ work.

Since the scientists know that the monocytes exit from the blood vessels in the bone marrow and enter into general blood circulation, eventually reaching the sites of inflammation – the AAA – Khan proposes “closing the door” to stop the out-of-control influx of these monocytes.

“Our plan is to target the bone marrow blood vessels and close the path through which these monocytes would exit the bone marrow. By closing this door, we hope to reduce inflammation and the symptoms, and other pathologies that are caused by chronic inflammation like AAA.”

But it’s not about stopping the flow of monocytes permanently. After all, the monocytes do perform that essential role of fighting infection in the body. So Khan’s technology is programmed to be a temporary therapy.

“I call it ‘on-demand.’ Our angle is to use this smart nanotechnology to send in multiple instruction sets to the bone marrow blood vessels and close the doors so the monocytes won’t come out. Once we have controlled the monocytes creating the inflammation, the nanotechnology stops the therapy to allow the monocytes to exit through the normal process and do their work in maintaining health by fighting infection.”

Khan’s smart technology also performs another important function. While he believes it will stop the release of monocytes to create inflammation, his nanotechnology is also designed to target a gene called “colony stimulating factor 1” (CSF1).

CSF1 is essential in generating monocytes. While the smart nanotechnology will be able to stop the release of monocytes to the bloodstream, the monocytes will continue to build up in the bone marrow, thus creating an eventual surge of them once the therapy is stopped. “So we will be working on slowing down the function of CSF1 to create monocytes in the bone marrow. That’s why we call our nanotechnology a multigene control. It can co-ordinate many different actions.”

For Robbins, the partnership with Khan is the reason he values Medicine by Design’s focus on collaboration.

“My role as a basic researcher is to investigate what is happening in this area of cardiovascular disease. So, we conducted various experiments and have modelled the condition in mice. But with Omar, we can take the next steps and figure out not just what is happening, but why, and, even more importantly, what we can do about it. Through Medicine by Design, my days of just wanting to do the science are over. I have a real interest in what this all means and the more applied clinical side.”

And for Khan, the collaboration is equally beneficial.

“My specialty is nanotechnology. Clint, Myron and Jason are the ones who know about monocytes and biology. So coming back to Toronto and connecting with them because of Medicine by Design is enabling me to hit the ground running and keep moving. With their animal models, we can begin to prove that our technology can work to improve people’s health.”

Health system needs to plan now for adoption of regenerative medicine therapies: U of T researchers

Christopher.Sorensen — Mon, 17 Aug 2020 16:41:12 +0000

Health system needs to plan now for adoption of regenerative medicine therapies: U of T researchers

Christopher.Sorensen Mon, 08/17/2020 - 12:41

Cutline

A new paper, drawing on a workshop hosted by U of T's Medicine by Design and others, says work needs to be done now to ensure regenerative medicine therapies are safe, effective, affordable and available to patients who need them (photo by Kenneth Chou)

Ann Perry

Topic

Our Community

CCRM

Faculty of Applied Science & Engineering

Faculty of Medicine

Global

Medicine by Design

Regenerative Medicine

University Health Network

Regenerative medicine holds the potential to revolutionize health care, but critical work needs to be done now to ensure the new therapies will be safe, effective, affordable and widely available to patients who need them.

That is one of the key conclusions of a paper published recently in Cell & Gene Therapy Insights that outlines the recommendations of an international workshop hosted by Medicine by Design at the ��߲ݴ�ý in collaboration with CCRM, the Toronto Health Economics and Technology Assessment Collaborative (THETA) at University Health Network (UHN), and Loughborough University in the U.K.

“As more regenerative medicine therapies move closer to the clinic, now is the time to engage policy-makers, governments, health-care providers and other stakeholders in these important conversations,” said Murray Krahn, the paper’s corresponding author and director of THETA.

“Laying this groundwork early will ensure our health-care system can adopt and implement regenerative medicine therapies efficiently and effectively, and in ways that align with the social values of Canadians,” added Krahn, who is also an attending physician at UHN and a professor at U of T’s Leslie Dan Faculty of Pharmacy and the Faculty of Medicine.

Funded by a $114-million grant from the federal government’s Canada First Research Excellence Fund, Medicine by Design brings together more than 130 researchers from across U of T and its affiliated hospitals to advance and accelerate regenerative medicine discoveries. As part of its mandate, it convened the June 2019 workshop that led to the paper, bringing together 37 researchers, clinicians, ethicists, policy-makers and industry leaders from Canada and the U.K. to discuss challenges in the adoption of regenerative medicine therapies.

The challenges include how to generate robust data when the number of patients enrolled in clinical studies may be small and how to determine if these therapies will be effective over the long-term.

Other key questions are how much these therapies should cost, who should pay for them and whether the often hefty price tag of novel therapies justifies the clinical benefit compared with existing treatments. These considerations are particularly important in countries with publicly funded health-care systems, such as Canada, where resources are limited. Ethical and social issues such as accessibility and patient experience also formed part of the workshop discussions.

Workshop participants discussed lessons learned from recent regulatory approval and implementation of a handful of CAR T-cell therapies, which re-engineer the patient’s immune system to fight certain types of cancer, and how they might be applied to regenerative medicine therapies.

“The pivotal next steps for future working groups to tackle revolve chiefly around addressing the evidence generation issues, relevant stakeholder engagement, targeted policy-maker engagement and understanding future payment system mechanisms,” the paper concludes. Its co-authors are: Maya Chaddah, a freelance science communicator; Allison Brown, director, strategy and translation at Medicine by Design; Siofradh McMahon, senior manager, clinical translation and regulatory affairs at CCRM; James Kusena, a PhD candidate at the Centre for Biological Engineering and Wolfson School of Mechanical, Electrical and Manufacturing Engineering at Loughborough University in the U.K. and an alumnus of Medicine by Design’s Summer by Design program; Karen Bremner, a research associate at THETA; and Ann Perry, associate director, administration, at Medicine by Design.

Krahn has convened a working group, made up of some of the workshop participants and others, to continue working on some of these issues. Early conversations have focused on creating a database for all regenerative medicine projects that will allow researchers to study their economic and clinical benefits compared with current therapies. As well, the group will explore the use of early health technology assessment methods.

Medicine by Design is also actively driving policy discussions. Affordability and accessibility form one of six topics Medicine by Design has invited researchers to address through its Grand Questions Program. Launched in July, the program is investing $3 million in bold ideas and developing transformative solutions that will be of critical importance to regenerative medicine over the next 20 years.

“If regenerative medicine therapies are to become the new standard of treatment for many diseases, we need to examine critically how they will intersect with regulators, policy-makers, payers and patients,” said Michael Sefton, executive director of Medicine by Design and a U of T University Professor in the Institute of Biomedical Engineering and the department of chemical engineering and applied chemistry in the Faculty of Applied Science & Engineering. “Through this paper and our Grand Questions Program, Medicine by Design and our partners are leading this conversation.”

Medicine by Design builds on decades of made-in-Canada excellence in regenerative medicine dating back to the discovery of stem cells in the early 1960s by Toronto researchers James Till and Ernest McCulloch. Regenerative medicine uses stem cells to replace diseased tissues and organs, creating therapies in which cells are the biological product. It can also mean triggering stem cells that are already present in the human body to repair damaged tissues or to modulate immune responses. Increasingly, regenerative medicine researchers are using a stem cell lens to identify critical interactions or defects that prepare the ground for disease, paving the way for new approaches to preventing disease before it starts.

Medicine by Design draws hundreds to annual research event, praise from federal innovation minister

Christopher.Sorensen — Mon, 09 Dec 2019 14:51:21 +0000

Medicine by Design draws hundreds to annual research event, praise from federal innovation minister

Christopher.Sorensen Mon, 12/09/2019 - 09:51

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Michael Sefton (centre), the executive director of Medicine by Design, says the regenerative medicine initiative wouldn't have been possible without the support of the federal government, which provided a $114-million grant (photo by Neil Ta)

Ann Perry

Topic

Our Community

Centre for the Commercialization of Regenerative Medicine

Chemistry

Faculty of Medicine

Faculty of Applied Science & Engineering

Faculty of Arts & Science

Institute of Biomaterials and Biomedical Engineering

Leslie Dan Faculty of Pharmacy

MaRS

Medicine by Design

Mount Sinai Hospital

Regenerative Medicine

Research & Innovation

Vivek Goel

Federal innovation, science and industry minister Navdeep Bains congratulated the ��߲ݴ�ý’s Medicine by Design community on its successes and affirmed the government’s commitment to science “as the foundation of innovation” at the regenerative medicine initiative’s annual research symposium.

“Your research will have a transformational impact on how we treat many common diseases, such as stroke, diabetes and liver failure, creating better health outcomes for all Canadians,” Bains said in a video message to the audience of 350 researchers, students, and industry and government representatives who gathered at the MaRS Discovery District last week.

“As the minister responsible for science and innovation, I look forward to working with the medical science sector to help Canadians live healthier lives and push the boundaries of innovation.”

Bains highlighted the federal government’s support of Medicine by Design through a $114-million grant from the Canada First Research Excellence Fund, and pointed to the 2018 budget as “the biggest reinvestment in fundamental research in Canadian history.”

The symposium, which marked the mid-point of Medicine by Design’s seven-year federal grant, focused on the role of technology in advancing biological insights and driving innovation, and noted the new portfolio of cross-disciplinary, cross-institutional projects the initiative announced in October. Speakers included high-profile international experts in regenerative medicine and cell therapy, including: Nancy Allbritton, a professor of bioengineering at the University of Washington; Joseph Gold, senior director of manufacturing at the Center for Biomedicine & Genetics at City of Hope in California; and Dr. Markus Grompe, a professor at Oregon Health & Science University.

“Medicine by Design perfectly reflects our belief that it is at the convergence of cross-disciplinary excellence that the next truly game-changing discoveries in research and innovation will take place,” said Vivek Goel, U of T’s vice-president, research and innovation, and strategic initiatives. “And it is a flagship example of the types of strategic, cross-divisional initiatives the ��߲ݴ�ý will continue to build.”

In addition to Medicine by Design, examples of such initiatives at U of T include PRiME, a precision medicine initiative, and the Schwartz Reisman Institute for Technology and Society.

“There are very few universities in the world where these kinds of initiatives can take flight, and U of T is one of them,” Goel added.

Medicine by Design brings together more than 130 principal investigators at U of T and its affiliated hospitals who are collaborating at the convergence of life and physical sciences, engineering, medicine and computer science to catalyze transformative discoveries in regenerative medicine and accelerate them toward the clinic. It builds on decades of made-in-Canada excellence in regenerative medicine dating back to the discovery of stem cells in the early 1960s by Toronto researchers James Till and Ernest McCulloch.

“The success we have achieved at Medicine by Design has been made possible in large part to the tremendous efforts of the federal government and the Canada First Research Excellence Fund,” said Michael Sefton, executive director of Medicine by Design, a University Professor at the Institute of Biomaterials & Biomedical Engineering (IBBME), and the Michael E. Charles Professor in the department of chemical engineering and applied chemistry.

“As we advance our research agenda, we are positioning these breakthrough discoveries to have the greatest impact on patients.”

Michael May, CEO of the Centre for Commercialization of Regenerative Medicine, hosts a panel discussion at Medicine by Design’s (photo by Neil Ta)

Translating research discoveries into new therapies, products and companies was a prominent theme at the event and will be a key focus for Medicine by Design over the next three years. A panel discussion moderated by Michael May, CEO of the Centre for Commercialization of Regenerative Medicine, and featuring speakers from GE Healthcare, Novartis Canada, AllosteRx Capital, Toronto Innovation Acceleration Partners and St. Michael’s Hospital, explored the challenges and opportunities inherent in this process. The discussion highlighted the unique strengths of Toronto’s regenerative medicine ecosystem, including: a world-leading public research university with broad strengths in medicine, life and physical sciences, as well as engineering; an expansive network of affiliated academic and community hospitals; expertise in translation, scale-up and manufacturing; and strong relationships with government.

Shana Kelley, a University Professor in the departments of chemistry, pharmaceutical sciences and biochemistry, and at IBBME, spoke about the new team project she is leading, which aims to identify and modulate cell differentiation bottlenecks.

“Medicine by Design has been career-changing for me,” Kelley said. “It has given me opportunities to connect with outstanding collaborators with whom I would not otherwise have had the chance to work.”

The symposium also offered an opportunity for 40 trainees to present their research during a poster session. Louise Moyle, a post-doctoral researcher in the laboratory of Penney Gilbert, an associate professor at IBBME, won first place. David Philpott, a PhD candidate in Kelley’s lab, placed second, while Alba Marin, a post-doctoral researcher in the lab of Professor Cristina Amon in the department of mechanical and industrial engineering, came third. The prizes were sponsored by StemCell Technologies Inc.

Jeffrey Harding, a post-doctoral researcher in the lab of Andras Nagy, a senior investigator at the Lunenfeld-Tanenbaum Research Institute at Sinai Health System, won the BlueRock Therapeutics prize for the poster with the greatest translational potential.

Medicine by Design to accelerate regenerative medicine discovery and translation with new $20-million investment

davidlee1 — Fri, 11 Oct 2019 15:52:34 +0000

Medicine by Design to accelerate regenerative medicine discovery and translation with new $20-million investment

davidlee1 Fri, 10/11/2019 - 11:52

Cutline

Freda Miller (left), a senior scientist at the Hospital for Sick Children, and University Professor Shana Kelley of the Leslie Dan Faculty of Pharmacy are leading two of the teams that Medicine by Design is funding

Ann Perry

Jovana Drinjakovic

Donnelly Centre for Cellular & Biomolecular Research

Faculty of Applied Science & Engineering

Faculty of Arts & Science

Faculty of Medicine

Gene Therapy

Institute of Biomaterials and Biomedical Engineering

Leslie Dan Faculty of Pharmacy

Medicine by Design

Meric Gertler

Regenerative Medicine

Research & Innovation

Stem Cells

Medicine by Design is strengthening the ��߲ݴ�ý as a global leader in regenerative medicine with a new investment of as much as $20 million in research that will accelerate stem cell and gene therapy, advance understanding of how the body repairs itself and generate new technologies that will propel the field for decades.

The three-year awards will support as many as 12 multi-disciplinary research teams across U of T and its affiliated hospitals that are working at the convergence of engineering, medicine and life and physical sciences. These teams are leading the development of stem cell-based strategies to replace damaged heart and liver tissue and induce the body to self-repair damaged nerve and muscle, as well as tackling key challenges in the field such as the lack of control in producing specific tissue types from stem cells, with the goal of turning discoveries into new therapies, products and companies sooner.

“Medicine by Design has generated breakthroughs that are transforming regenerative medicine and sparking tremendous activity throughout Canada’s life sciences ecosystem,” said U of T President Meric Gertler. “This new investment will build on these advances, lay the foundation for translating these innovations into tangible benefits to patients and society, and advance Toronto’s position as the leading international centre of excellence in regenerative medicine for decades to come.”

Funded by a $114-million grant from the federal government’s Canada First Research Excellence Fund, Medicine by Design is a strategic research initiative at U of T that is catalyzing transformative discoveries in regenerative medicine and accelerating them toward the clinic. It builds on decades of made-in-Canada excellence in regenerative medicine dating back to the discovery of stem cells in the early 1960s by Toronto researchers Drs. James Till and Ernest McCulloch.

This is the second time Medicine by Design has awarded large-scale funding for collaborative team projects. Research supported by the first round of Team Project awards (2016-2019) has already driven significant advances, including the first “map” of the human liver, which attracted further funding this year from the Chan Zuckerberg Initiative. Another Medicine by Design-funded team has developed “safe cells” that are programmed to be killed if they become harmful, a key advance in improving the utility of cell therapies.

Over the past three years, Medicine by Design-funded researchers have also launched 15 startups.

The new awards will build on these discoveries and continue to spur innovations that will push the field forward, said Michael Sefton, executive director of Medicine by Design.

“By bringing together leading investigators across disciplines and institutions to confront the most challenging problems in the field, we have created new collaborations that have fundamentally changed how the regenerative medicine community in Toronto works together,” said Sefton, a University Professor at the Institute of Biomaterials & Biomedical Engineering (IBBME) and the Michael E. Charles Professor in the department of chemical engineering and applied chemistry.

“These new projects all have significant potential to achieve transformative and globally competitive outcomes and advance groundbreaking discoveries toward the clinic, transforming how we treat many devastating diseases.”

One team led by Shana Kelley, a University Professor at the Leslie Dan Faculty of Pharmacy, is developing a suite of advanced tools to enable researchers to gain new insights into how stem cells differentiate into any specialized cell type.

Freda Miller, a senior scientist at the Hospital for Sick Children (SickKids), heads a team that is developing a platform that will enable the rapid identification and testing of signals that activate stem cells in muscle and brain to repair damaged tissue, which could transform the treatment of muscular dystrophy and demyelinating disorders, such as multiple sclerosis.

Restoring heart function after heart failure is the focus of another team led by Michael Laflamme, a senior scientist at the McEwen Stem Cell Institute at University Health Network (UHN).

“We’ve come a long way from deriving stem cell-derived heart muscle cells in the Petri dish to optimizing them now for eventual use in patients,” said Laflamme. “This massive effort would not have been possible without Medicine by Design, which brought us all together toward a common goal of finding a cure for heart failure.”

Medicine by Design selected projects for funding after an extensive evaluation process, which included consultation with the research community, external peer review and scientific and strategic advice from Medicine by Design’s scientific advisory board.

Other funded research includes projects aimed at:

Using stem cells to regenerate damaged livers, led by Gordon Keller, director of the McEwen Stem Cell Institute at UHN, in collaboration with Ian McGilvray, a senior scientist at the Toronto General Hospital Research Institute (TGHRI) and a transplant surgeon at UHN, Sonya MacParland, a scientist at TGHRI specializing in liver immunology, Molly Shoichet, a University Professor in the department of chemical engineering and applied chemistry, Axel Guenther, an associate professor in the department of mechanical and industrial engineering, Gary Bader, a professor in the Donnelly Centre for Cellular and Biomolecular Research, and Christine Bear, a senior scientist at SickKids.

Reprogramming brain cells to treat amyotrophic lateral sclerosis and stroke, led by Cindi Morshead, a professor and chair of the division of anatomy in the department of surgery, in collaboration with: Isabelle Aubert and Carol Schuurmans, senior scientists at the Sunnybrook Research Institute, Maryam Faiz, an assistant professor in the department of surgery, and Melanie Woodin, a professor in the department of cell and systems biology and dean of U of T’s Faculty of Arts & Science.

Understanding how immune cells function in healthy and damaged blood vessels, led by Clint Robbins, a scientist at TGHRI, in collaboration with Myron Cybulsky and Jason Fish, both senior scientists at TGHRI.

Studying how material exchange – a process whereby cellular material from transplanted cells is transferred to host cells – could play a role in improving outcomes of cell-based retinal therapy aimed at preserving and restoring sight. This project is led by Molly Shoichet in collaboration with Derek van der Kooy, a professor at the department of molecular genetics and the Donnelly Centre, Valerie Wallace, a senior scientist at the Krembil Research Institute at UHN, and Julie Lefebvre, a scientist at SickKids.

Additional projects, including those focused on the effect of aging on cardiac disease, organoids, diabetes and organ repair, are under review, with final decisions expected by December.

Advanced manufacturing supercluster invests in potentially life-saving gene therapies

rahul.kalvapalle — Thu, 22 Aug 2019 14:11:17 +0000

Advanced manufacturing supercluster invests in potentially life-saving gene therapies

rahul.kalvapalle Thu, 08/22/2019 - 10:11

Cutline

Navdeep Bains, the federal minister of innovation, science and economic development, speaks Wednesday at an event where the advanced manufacturing supercluster's first funded project, focused on genetic treatments, was announced (photo by Johnny Guatto)

Rahul Kalvapalle

Topic

Our Community

Advanced Manufacturing

Centre for the Commercialization of Regenerative Medicine

Faculty of Applied Science & Engineering

Gene Therapy

Regenerative Medicine

Research and Innovation

The organization that runs Canada’s advanced manufacturing supercluster – which includes the ��߲ݴ�ý – has announced its first funded project: a consortium devoted to producing special viruses that can deliver genetic treatments to people suffering from late-stage cancers and rare genetic disorders.

Next Generation Manufacturing Canada (NGen), a not-for-profit that oversees the supercluster and includes Faculty of Applied Science & Engineering Dean Emerita Cristina Amon on its board, said it will contribute $1.89 million towards the project.

The project, led by Toronto-based company iVexSol Canada, will see iVexSol forge a partnership with the Centre for Commercialization of Regenerative Medicine (CCRM), which is hosted at U of T and counts Vice-President, Research and Innovation, and Strategic Initiatives Vivek Goel among its directors. Other partners include GE Healthcare and Vancouver-based biotech company Stemcell Technologies.

Its mission is to produce lentiviral vectors – retroviruses that are crucial to the development of cell and gene therapies to fight cancer and various genetic disorders – in far greater quantities and at a significantly lower cost than legacy methods by using iVexSol's clinically proven advanced manufacturing process.

Navdeep Bains, the federal minister of innovation, science and economic development, hailed the CCRM-linked project as an example of how the advanced manufacturing supercluster can drive potentially life-saving innovations.

“We all know someone who has had to battle cancer. This project and its results will give new hope to those family members, friends, the very people battling late-stage cancers,” Bains said during an event at the MaRS Discovery District on Wednesday.

“This project is an important first step for the game-changing work of the supercluster and will drive innovation in the treatment of diseases and genetic disorders once considered untreatable.”

Researchers work at the Centre for Commercialization of Regenerative Medicine, which supports the development of technologies focused on cell and gene therapies (photo courtesy of CCRM)

The advanced manufacturing supercluster is one of five superclusters announced by the federal government in early 2018. Superclusters – networks of companies, academic and research institutions and other innovation actors – are part of the government’s broader innovation strategy to invest in industries where Canadian companies are positioned to emerge as global leaders.

CCRM’s contribution to the gene therapies operation will be to provide manufacturing infrastructure and technical services.

Michael May, president and CEO of CCRM, said the organization was excited to offer its expertise to bring the project to fruition.

“This initiative aligns perfectly with CCRM’s purpose to revolutionize health care by solving the big problems in regenerative medicine, including cell and gene therapy,” said May, who earned his PhD in chemical engineering from U of T in 1998.

Bains noted that advanced manufacturing activities such as the lentiviral vector initiative have the potential to spawn economic benefits for generations.

“This is about making sure that innovation benefits Canadians and also creates economic growth and job opportunities,” Bains said.

“In Canada, we already have a strong footprint in manufacturing, and 10 per cent of the Canadian economy is linked to manufacturing. But today, it is advanced manufacturing that is revolutionizing how we produce goods, which are often products that promise to transform our lives.

“Globally, advanced manufacturing is an industry that’s valued in the billions of dollars – I’m talking hundreds of billions.”

The investment in iVexSol is expected to create over 450 jobs, while the NGen supercluster as a whole is estimated to create over 13,500 jobs and add more than $13.5 billion to the Canadian economy over the coming decade.

Gillian Hadfield appointed inaugural director of U of T’s Schwartz Reisman Institute for Technology and Society and Schwartz Reisman Chair in Technology and Society

Christopher.Sorensen — Fri, 26 Jul 2019 16:23:00 +0000

Gillian Hadfield appointed inaugural director of U of T’s Schwartz Reisman Institute for Technology and Society and Schwartz Reisman Chair in Technology and Society

Christopher.Sorensen Fri, 07/26/2019 - 12:23

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In her new role, Gillian Hadfield will draw on her varied background – in economics and law, humanities, business and high tech – to help ensure technological innovation is implemented fairly and equitably in society (photo courtesy of Gillian Hadfield)

Geoffrey Vendeville

Topic

Our Community

Schwartz Reisman Innovation Centre

Schwartz Reisman Institute for Technology and Society

Artificial Intelligence

Biotechnology

Computer Science

Creative Destruction Lab

Economics

Faculty of Arts & Science

Faculty of Information

Regenerative Medicine

Robotics

Rotman School of Management

Social Sciences

Vector Institute

Facial recognition technology. Algorithms that decide who is a good candidate for a loan or medical procedure. Interactive robots in workplaces and seniors’ homes.

These are just a few examples of the many new and emerging technologies that promise to reshape society in profound and, perhaps, unexpected ways – often raising thorny ethical questions in the process.

As the inaugural director of the ��߲ݴ�ý’s new Schwartz Reisman Institute for Technology and Society and the inaugural Schwartz Reisman Chair in Technology and Society, Gillian Hadfield will draw on her varied background – in economics and law, humanities, business and high tech – to help ensure technological innovation is implemented fairly and equitably in societies around the world.

“Technologies are a means to an end,” says Hadfield, who is a U of T professor in the Faculty of Law and the Rotman School of Management.

“And the end must be a world that is better, safer, kinder, fairer for us all.”

The Schwartz Reisman Institute for Technology and Society draws on U of T’s across-the-board strengths in sciences, social sciences and humanities to help foster cross-disciplinary solutions to the profound challenges spawned by rapid technological shifts. The institute was established thanks to a landmark $100-million donation – the largest in U of T’s history – by business leaders and philanthropists Gerald Schwartz and Heather Reisman. The gift will also be used to help break ground on the Schwartz Reisman Innovation Centre at the northeast corner of College Street and University Avenue, a new space for students and faculty innovators working in business, computer science and biotechnology, among other fields.

Learn more about the Schwartz Reisman Institute for Technology and Society

“U of T researchers are leaders in fields as diverse as machine learning, regenerative medicine, philosophy, and culture and communications,” says U of T President Meric Gertler.

“The Schwartz Reisman Institute for Technology and Society will leverage these strengths to help us understand the impact of technology on society – and, indeed, on humanity itself. The work of the institute will also explore the ways in which public policy, politics, and culture can shape the development and application of technology to serve societal ends.

“It is an ambitious and important mandate, and we are thrilled to welcome Professor Hadfield to her new role as the institute’s inaugural director and chair.”

Hadfield re-joined U of T’s Faculty of Law last year after teaching for 17 years at the University of Southern California. She was originally on faculty at U of T between 1995 and 2001.

The native of Oakville, Ont. has a bachelor’s degree in economics from Queen’s University and a law degree and a PhD in economics from Stanford University. She clerked for Chief Judge Patricia Wald on the U.S. Court of Appeals, D.C. Circuit, and has held visiting professorships or fellowships at Harvard, Columbia, NYU, Chicago, and Stanford.

Hadfield was a fellow at Stanford’s Center for Advanced Study in the Behavioral Sciences, an experience she says has influenced her vision for U of T’s new institute. As an example of the serendipity that can happen when scholars of a wide variety of fields come together, she recalls hearing a talk by an art historian on the complex geometry of Gothic architecture during her fellowship that meshed with her own ideas on economies and how they pass down knowledge. The lecture focused on how much of the know-how needed to reproduce intricate Gothic buildings was bound up in practice rather than in plans and sketches.

“The complexity was rooted in simplicity and it was knowing what steps to take – rather than the math of the whole – that generated the result,” she says. “When masters stopped building the buildings, the knowledge was lost. I remember this point converging with my own thinking about how economies find and transmit knowledge, and how that can also be rooted in practices and not just theory.”

She hopes researchers at the Schwartz Reisman Institute will similarly find inspiration and points of connection in each other’s work, sparking new ideas and maybe even whole new branches of knowledge.

U of T is a particularly suitable home for such collaboration because it boasts world-leading scholars in a wide spectrum of disciplines, she adds.

“The ��߲ݴ�ý is a top-flight research university in so many different fields,” she says. “Our ambition for the institute is to knit together research across the sciences, social sciences, the humanities and other fields to find new, concrete solutions to make sure our emerging and powerful technologies go in the direction we want them to go.”

Vivek Goel, vice-president, research and innovation, and strategic initiatives, points out that U of T is one of the few universities in the world that ranks among the top schools in a wide range of subjects.

“U of T’s broad strength across disciplines makes it the ideal place to encourage a cross-pollination of ideas,” says Goel.

“It’s our job to find innovative ways to break down silos between disciplines so these different ideas and perspectives have the opportunity to collide and, hopefully, yield new avenues for research and scholarship, including for graduate students.”

The Schwartz Reisman Institute for Technology and Society is just one example of how U of T is seeking to encourage interdisciplinary approaches, having recently created a new senior administrative position tasked with seeding and scaling such initiatives.

Hadfield’s research spans different disciplines and addresses questions ranging from the philosophical to the mathematical. She has called for reforms to the legal system to reduce fees and other barriers faced by the roughly 80 per cent of people who go to court without a lawyer. She expanded on those ideas and the twin challenges of globalization and digitization in her 2017 book, Rules for a Flat World: Why Humans Invented Law and How to Reinvent it for a Complex Global Economy (a reference to Thomas Friedman’s bestseller The World Is Flat.) She has taught a course based on her book at U of T and co-led the Legal Design Lab (with her husband Dan Ryan, a professor at U of T’s Faculty of Information), an incubator-workshop bringing together students in law, engineering, business, design and information studies to come up with innovative solutions to problems involving access to justice. At Rotman, she teaches about AI and how to ensure its responsible development with the Creative Destruction Lab and the new Vector Institute for Artificial Intelligence-affiliated Master in Management Analytics.

In addition to research and teaching, Hadfield brings experience as a member of the World Economic Forum’s Global Future Council on Agile Governance, which focuses on “adaptive, human-centered, inclusive and sustainable” policy-making in the face of technological advancement. She is also deeply engaged in questions about rules and governance surrounding artificial intelligence as a policy adviser for Open AI in San Francisco, an adviser to courts and tech companies, and as a faculty affiliate at the Vector Institute.

One of her early goals as director of the Schwartz Reisman Institute for Technology and Society and Schwartz Reisman Chair in Technology and Society will be to build a “truly integrated, team-based approach to problem solving” by connecting researchers in different disciplines.

“One of the first things we will be doing is looking for people who are really interested in engaging with, and respectful of, approaches in other disciplines,” she says. “The first thing we can do is find those people and start to build that community of collaboration. That’s something that takes thoughtfulness and care.”

In the future, she wants the institute to be known around the world as the go-to place to learn about the technological challenges facing society and to convene to work on their possible solutions.

“I think it’s a great ambition that in 10 years, we’ll have generated new fields of research,” Hadfield says. “I’ll be asking, ‘Have we really created something where we have broken down the silos between disciplines and created truly cross-disciplinary approaches?’

“I’d like to see us being part of inventing a new way to do intellectual work. And with that, to have invented new ways to make sure that our powerful technologies develop in ways that serve humanity well.”

Leading researcher in regenerative medicine becomes first Medicine by Design scholar in residence

noreen.rasbach — Tue, 16 Jul 2019 15:57:06 +0000

Leading researcher in regenerative medicine becomes first Medicine by Design scholar in residence

noreen.rasbach Tue, 07/16/2019 - 11:57

Cutline

Professor Shulamit Levenberg is visiting the ��߲ݴ�ý beginning this week with a view toward identifying collaborative research opportunities (photo courtesy of Technion)

Ann Perry

Topic

Global Lens

Faculty of Applied Science & Engineering

Global

IBBME

Medicine by Design

Regenerative Medicine

Research & Innovation

Ted Rogers Centre for Heart Research

Professor Shulamit Levenberg, a leading interdisciplinary researcher in stem cells and tissue engineering at Technion-Israel Institute of Technology, has started her month-long appointment as Medicine by Design’s first scholar in residence.

While at the ��߲ݴ�ý, the dean of Technion’s Faculty of Biomedical Engineering will deliver a series of talks, meet with faculty members who have complementary research interests and engage with trainees, with a view toward identifying collaborative research opportunities.

“The goal of the Medicine by Design scholar in residence program is to invite top international investigators in regenerative medicine and related fields to Toronto to engage with our dynamic community, catalyze new collaborations and advance international partnerships,” said Michael Sefton, executive director of Medicine by Design, a University Professor at the Institute of Biomaterials and Biomedical Engineering (IBBME) and the Michael E. Charles Professor in the department of chemical engineering and applied chemistry.

“Professor Levenberg is a leader in her field and we hope her visit will strengthen a long and productive relationship.”

Levenberg’s visit will build on existing collaborations between Technion and U of T and its affiliated hospitals. Lyon Sachs, an alumnus of the Faculty of Applied Science & Engineering, has given $2 million to the university to accelerate joint research projects between U of T and Technion in biomedical and civil engineering. The McEwen Stem Cell Institute and the Peter Munk Cardiac Centre at University Health Network have also partnered with Technion to create a centre aimed at developing new ways to treat heart disease, with a focus on regenerative medicine.

Levenberg will deliver a talk on Thursday, July 18 at noon titled “Vascularization Dynamics in Engineered Tissues” as part of Medicine by Design’s Global Speaker Series. She will give another talk titled “Engineering Vascularized Tissue Constructs” on July 23 at 11 a.m., hosted by the translational biology and engineering program at the Ted Rogers Centre for Heart Research. She will also hold office hours at the Donnelly Centre for Cellular and Biomolecular Research, room 508, on the following dates:

Thursday, July 25 – 1 p.m. to 2 p.m.
Thursday, Aug. 1 – 1 p.m. to 2 p.m.
Wednesday, Aug. 7 – 1 p.m. to 2 p.m.

Levenberg earned her PhD at the Weizmann Institute of Science, where she focused on cell adhesion dynamics and signalling, and pursued her post-doctoral research in tissue engineering at the Massachusetts Institute of Technology in the lab of Professor Robert Langer. In 2004, she joined the Technion Faculty of Biomedical Engineering, where she conducts interdisciplinary research on stem cells and tissue engineering. She also serves as the director of the Technion Center for 3D Bioprinting and The Rina & Avner Schneur Center for Diabetes Research.

She spent a sabbatical year as a visiting professor at the Wyss Institute for Biology Inspired Engineering at Harvard University and a summer sabbatical (2017) at the University of Western Australia as a winner of the Raine Visiting Professor Award. Levenberg received the Krill Prize for excellence in scientific research, awarded by the Wolf Foundation, and was named by Scientific American as a “research leader” in tissue engineering for her seminal work on vascularization of engineered tissues. She also received the France-Israel Foundation Prize, the Italian Excellence for Israel Prize, the Teva Research Prize and the Juludan Prize. In 2018, she received the Rappaport Prize for Biomedical Sciences.

Levenberg has authored more than 100 publications and presented her work at more than 100 international conferences as an invited or keynote speaker. She is founder and chief scientific officer of two start-up companies in the areas of cultured meat and nanolitre arrays for rapid antimicrobial susceptibility testing. She is a member of the Israel National Counsel for Bioethics and is actively involved in training young scientists.

U of T's Medicine by Design invests $1.2 million to advance regenerative medicine research and translation

Christopher.Sorensen — Tue, 14 May 2019 21:05:07 +0000

U of T's Medicine by Design invests $1.2 million to advance regenerative medicine research and translation

Christopher.Sorensen Tue, 05/14/2019 - 17:05

Cutline

Leo Chou, an assistant professor at U of T’s Institute of Biomaterials & Biomedical Engineering and a Medicine by Design investigator, is leading one of four projects selected for the 2019 New Ideas Awards (Photo by Bill Dai)

Ann Perry

Topic

Our Community

Pediatrics

Donnelly Centre for Cellular & Biomolecular Research

Lunenfeld-Tanenbaum Research Institute

Chemical Engineering

Electrical & Computer Engineering

Faculty of Applied Science & Engineering

Fields Institute

Hospital for Sick Children

Immunology

Institute of Biomaterials and Biomedical Engineering

Laboratory Medicine and Pathobiology

Leslie Dan Faculty of Pharmacy

Mechanical & Industrial Engineering

Regenerative Medicine

Research & Innovation

Sunnybrook Hospital

surgery

U of T Scarborough

University Health Network

UTIAS

What can a swarm of drones tell us about how our bodies make blood? Can folding strands of DNA into origami-like structures help researchers engineer more targeted treatments for lupus and multiple sclerosis? What new insights can mathematical and computational modelling offer into how tissues and organs form?

These are just a few of the questions that nine research teams across the ��߲ݴ�ý and its affiliated hospitals are investigating thanks to $1.2 million in 2019 New Ideas and Seed Fund awards from Medicine by Design. The awards support basic and translational research aimed at advancing new concepts that are expected to be of critical importance to regenerative medicine in the coming decades, using tools such as synthetic biology and mathematical modelling.

“With these awards, we are pushing the frontiers of regenerative medicine by encouraging creativity, risk-taking and excellence at the convergence of science, engineering and medicine,” said University Professor Michael Sefton, who is executive director of Medicine by Design and a faculty member at the Institute of Biomaterials & Biomedical Engineering (IBBME) and the department of chemical engineering and applied chemistry.

“These projects exemplify the best of Medicine by Design by bringing people together across disciplines and institutions to tackle novel questions and test new approaches.”

Medicine by Design selected the nine funded projects from among 22 short-listed proposals, which were evaluated and ranked through an external peer review process. Sixty research teams at U of T and its affiliated hospitals submitted expressions of intent last fall in response to an open call.

Medicine by Design is a regenerative medicine research initiative at U of T with a mandate to accelerate transformational discoveries and translate them into new therapies for common diseases. It is made possible thanks in part to a $114-million grant from the Canada First Research Excellence Fund – the single-largest research award in U of T’s history.

New Ideas Awards

Leo Chou leads one of four projects selected for 2019 New Ideas Awards, which provide $100,000 per year for two years. Chou, an assistant professor at IBBME and a new Medicine by Design investigator, is collaborating with Bebhinn Treanor, an associate professor in the department of biological sciences at the U of T Scarborough, to study how DNA nanotechnology could be used to ramp up or dampen immune responses, offering new ways to treat disease.

The project elegantly fuses their diverse expertise. Chou uses a process known as DNA origami to pinch and “staple” a long strand of DNA at precise points to create a variety of nanoscale shapes that can arrange biomolecules into precise two- and three-dimensional patterns. Treanor, an immunologist, studies how antigens – fragments of viruses or bacteria with unique markers – trigger immune cells in our bodies called B cells to produce specific antibodies to bind to and inactivate the associated virus or bacteria. Both are intrigued by the fact that, in nature, antigens arranged in periodic spacing provoke a much more potent immune response than individual antigens.

Together, they plan to use Chou’s DNA nanostructures as building blocks to study how the layout, structure, and nature of an array of antigens can affect the dynamics and strength of B cell activation.

The immediate goal is to figure out the basic design principles. “Like all good, fundamental studies, it might open up a lot of doors,” said Chou, who earned his PhD at IBBME in 2014 and returned to U of T in January as a faculty member after a post-doctoral fellowship at the Wyss Institute at Harvard University and the Dana-Farber Cancer Institute in Boston.

“It might lead us to interesting biology that we just don’t understand, or haven’t discovered, yet.”

Ultimately, Chou and Treanor hope to create synthetically designed particles that can act as precision vaccines to heighten or dampen immune responses. This approach could lead to more targeted therapies for autoimmune diseases, such as lupus, arthritis and multiple sclerosis, in which the normal immune process goes haywire and mounts an attack on a person’s own cells. Chou also thinks their technology platform could be applied to better control the activation of other cell types, which could help enable cell-based therapies by making the cell-manufacturing process more efficient.

Other 2019 New Ideas projects include:

Dr. Robert Hamilton, a cardiologist and senior associate scientist at The Hospital for Sick Children (SickKids) and a professor in the department of paediatrics at U of T, is leading a project that aims to create precision immunotherapies for arrhythmogenic right ventricular cardiomyopathy. This heritable, autoimmune condition causes the myocardium, or heart muscle wall, to break down over time and can lead to sudden death. Sachdev Sidhu, a professor at U of T’s Donnelly Centre for Cellular and Biomolecular Research, is the co-investigator, and SickKids clinicians Dr. Donna Wall and Dr. Joerg Krueger are also part of the project team.
Dr. Sevan Hopyan, an orthopaedic surgeon and senior scientist at SickKids and an associate professor in the departments of molecular genetics and surgery at U of T, is making a computational tool to gain new insights into the physical processes that influence how embryonic tissues are organized and shaped. Known as morphogenesis, this process at the earliest stages of life remains poorly understood but could hold important clues for researchers developing regenerative medicine therapies. The co-investigator on this project is Yu Sun, a professor in the department of mechanical and industrial engineering at U of T, while Huaxiong Huang, the deputy director of the Fields Institute for Research in Mathematical Sciences, is collaborating.
Krishna Mahadevan, a professor in the department of chemical engineering and applied chemistry, is leading a team that aims to create new therapies for inflammatory bowel disease such as Crohn’s disease by engineering gut bacteria that can sense inflammation, and then secrete molecules that dampen it and promote regeneration of the intestinal lining. Combining synthetic biology and stem cell biology, the project also draws on the expertise of co-investigators Keith Pardee, an assistant professor in the Leslie Dan Faculty of Pharmacy and a Medicine by Design investigator, and Tae-Hee Kim, a scientist at SickKids and an assistant professor in U of T’s department of molecular genetics.

Seed Fund Awards

To increase the number of cutting-edge ideas it invests in, Medicine by Design created a new award this year called the Seed Fund Award, which provides $75,000 for one year to each of five projects.

Angela Schoellig (left) leads one of these projects, which is forging innovative ties between biomedical engineering and robotics. An assistant professor at U of T’s Institute for Aerospace Studies, she works at the interface of robotics, controls and machine learning, with research interests in self-driving vehicles and autonomous aerial vehicles, or drones.

Schoellig is using her award funding to study complex collective behaviour in living and non-living systems. Known as emergence, the phenomenon refers to the dynamic evolution of a system to develop complexity that cannot be easily predicted from the properties of its individual parts. In nature, a common example of emergence is murmuration, which occurs when hundreds of birds congregate and fly in organized, swooping patterns.

Schoellig and co-investigator Peter Zandstra, a University Professor at IBBME, are combining their respective expertise in robotic drones and blood-forming systems to gain new insights into emergence that could lead to advances in both fields. They hope that identifying common elements in these diverse systems will help them understand how a collection of individual entities in a disordered state develops complex, co-ordinated activities, ultimately advancing the capacity to predict and even control desirable emergent behaviour. Such findings could have many applications, including improving the reconstitution of healthy blood systems in patients who have undergone stem cell transplants. The research could also enhance the ability of robots to perform collaborative tasks in dynamic environments, such as airspace defence, search and rescue, and package delivery. Zandstra is also director of the School of Biomedical Engineering and the Michael Smith Laboratories at the University of British Columbia.

The other four successful Seed Fund Award projects range from brain organoids to new strategies to treat hearing loss.

Dr. Peter Carlen, a neurologist and senior scientist at the Krembil Research Institute at University Health Network (UHN) and a professor in U of T’s departments of medicine and physiology, as well as IBBME, is leading a project aimed at creating personalized treatments for the one-third of epilepsy patients whose disease does not respond to drugs. He plans to do this by generating cerebral organoids – brain-like mini-organs grown in a dish – from induced pluripotent stem cells derived from patients with drug-resistant epilepsy. His team will then use these organoids to study why the patients have not responded to medication, and to determine optimal pharmacotherapy options. Co-investigators on the project are Cathy Barr, a senior scientist at Krembil and SickKids and a professor in U of T’s department of psychiatry, and Roman Genov, a professor in U of T’s department of electrical and computer engineering.
Sarah Crome, a scientist at UHN, an assistant professor at U of T’s department of immunology and a Medicine by Design investigator, heads a project investigating whether immune cells known as innate lymphoid cells that reside in tissues can be harnessed to promote regeneration, prevent rejection and ultimately improve the success of cell-based immune therapies.
Alain Dabdoub, a senior scientist at Sunnybrook Research Institute and an associate professor in the departments of otolaryngology and laboratory medicine and pathobiology at U of T, leads a project aimed at regenerating the auditory neurons that transmit sound from the inner ear to the brain as a strategy to reverse hearing loss. Building on work he has already performed in mice in vitro, Dabdoub will investigate how to convert glial cells in a mouse model of neuropathy as well as human glial cells in vitro into auditory neurons.
Miguel Ramalho-Santos, a senior investigator at the Lunenfeld-Tanenbaum Research Institute at Sinai Health System, a professor at U of T’s department of molecular genetics and a Medicine by Design investigator, is using his Seed Fund Award to study whether the way genes are packed inside the nucleus of human pluripotent stem cells affects their ability to generate cerebral organoids, a tool that holds potential to model neurological diseases and test medications outside the body.

With these new awards, Medicine by Design funds more than 130 investigators across U of T and its affiliated hospitals.