Research & Innovation. Faculty of Arts & Science

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

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

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

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

Cutline

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

Brianne Tulk

Topic

Our Community

Insulin 100

Temerty Faculty of Medicine

Diabetes

Mount Sinai Hospital

Research & Innovation

Research & Innovation. Faculty of Arts & Science

Daniel Drucker is unraveling a medical mystery.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Nvidia CEO Jensen Huang calls Canada's AI talent 'incredible,' a key resource

Christopher.Sorensen — Mon, 24 Sep 2018 04:00:00 +0000

Nvidia CEO Jensen Huang calls Canada's AI talent 'incredible,' a key resource

Christopher.Sorensen Mon, 09/24/2018 - 00:00

Cutline

Jensen Huang, the co-founder and CEO of graphic chip-maker Nvidia, was in Toronto to celebrate the launch of the Silicon Valley firm's new AI lab, led by U of T Assistant Professor Sanja Fidler (photo by Chris Sorensen)

Chris Sorensen

Topic

Global Lens

Artificial Intelligence

Computer Science

Geoffrey Hinton

Global

Research & Innovation. Faculty of Arts & Science

U of T Mississauga

Vector Institute

Vivek Goel

Canada has all the ingredients needed to take advantage of the coming artificial intelligence revolution – a shift that promises to supercharge the growth of a wide range of industries from transportation to health care, according to Jensen Huang, the CEO of graphics chip giant Nvidia.

Huang, who spoke at an event celebrating Nvidia’s new Toronto AI lab, lauded Canada for its potent mix of top AI researchers and an innovation sector that encourages collaboration between business, academia and government.

“The [AI] talent here is incredible,” Huang told a packed auditorium at the MaRS Discovery District last Friday.

“Canada is gifted to have one of the world’s most important resources today.”

One of those top AI minds is the University of Toronto's Sanja Fidler, an expert in computer vision and applied machine learning. Back in June, Nvidia revealed it had tapped Fidler to be its new director of AI research in Toronto while remaining an assistant professor at the University of Mississauga's department of mathematical and computational sciences. Fidler is one of several U of T researchers whose work has contributed to the university's reputation as a leading global hub of AI research in recent years.

While Nvidia’s graphics processing units, or GPUs, were originally designed for video games, the chips have increasingly become the hardware of choice on which to run data-intensive machine learning applications. That, in turn, has propelled Nvidia into a range of high-growth sectors, ranging from advanced robotics to self-driving cars, and has put it in competition for top talent alongside firms like Google, Uber, Samsung and LG – all of which have established AI resarch labs in Toronto with a connection to U of T.

Sanja Fidler, an assistant professor at U of T Mississauga’s department of mathematical and computational sciences, is the head of Nvidia's Toronto AI lab (photo by Chris Sorensen)

Huang, who co-founded Nvidia a quarter century ago, laid out his vision of how AI will transform a wide range of businessness and industries, predicting it would unleash a period of unprecendented economic growth.

“AI is the automation of automation,” Huang said. “It has the power to drive productivity at a rate nobody has ever seen before.”

Other speakers noted Toronto's emergence as a hub of AI research activity was no accident.

“It didn’t just happen magically,” Vivek Goel, U of T’s vice-president of research and innovation, reminded the audience before Huang took the stage.

Supported by government funding, pioneers like U of T University Professor Emeritus Geoffrey Hinton, now known as the “godfather” of deep learning, and his students toiled away for decades on a then unpopular branch of AI that attempted to mimic how the human brain learns. At the same time, Canada quietly began building infrastructure needed to transform its research into products and services in the commercial realm. More recently, U of T partnered with industry and the federal and provincial governments to launch the Vector Institute for Artificial Intelligence, which is designed to attract and retain top AI talent.

The breadth of research taking place at U of T, one of the world's top-ranked public universities, has also translated into an AI advantage for Canada's largest city, according to Goel. That's because it allows AI researchers to work across disciplines with experts in medicine, law and even music to create novel AI applications. Goel cited the following U of T startups as examples: Deep Genomics, which uses machine learning to find treatments for genetic diseases, and Blue J Legal, which uses machine learning to predict the outcome of tax and employment law cases.

The end result has been a boom in Toronto’s tech sector, which added more jobs than any other North American city last year, according to a recent report by commercial real-estate firm CBRE.

Geoffrey Hinton, U of T University Professor Emeritus and the “godfather” of deep learning, on stage with Nvidia CEO Jensen Huang (photo by Chris Sorensen)

“Ontario is very proud of its AI roots – the godfather of AI, Geoffrey Hinton, did much of his research at the University of Toronto and was instrumental, along with many others, with the founding of the Vector Institute of Artificial Intelligence,” said Jim Wilson, Ontario’s minister of economic development, job creation and trade.

“In a short period of time, Vector has become the catalyst for AI investments in Ontario by companies like Uber, Google Brain, LG, Accenture, Etsy, Samsung and, of course, Nvidia.”

U of T, meanwhile, has endeavoured to work out formal and informal partnerships with many of those companies. The arrangements typically allow researchers to split their time between academia and the private sector, giving them access to a wider range of resources.

Goel called it a “brain retain” strategy.

“It's a great pleasure to welcome Nvidia into the ecosystem we've been building,” he said.

Looking for a non-profit CEO? Choose a teddy bear, not a shark: University of Toronto study

krisha — Wed, 22 Jun 2016 14:39:43 +0000

Looking for a non-profit CEO? Choose a teddy bear, not a shark: University of Toronto study krisha Wed, 06/22/2016 - 10:39

Peter McMahon

Author legacy

Peter McMahon

Topic

Breaking Research

Psychology

Research & Innovation. Faculty of Arts & Science

Nicholas Rule

Subheadline

Not-for-profits raise more money when leader looks less powerful, research finds

Having the face of a leader may depend on whether the enterprise being led is a for-profit business or a non-profit organization, new research from the University of Toronto has found.

It's the latest finding by the social perception and cognition experts who've advised us on:

how to tell a trustworthy face from an untrustworthy face

how much weight we'd need to lose to seem more attractive to others

what our selfie habits reveal about us

In a paper entitled “Predicting Firm Success from the Facial Appearance of Chief Executive Officers of Non-Profit Organizations,” published in the journal Perception, Daniel Re, a postdoctoral fellow and Nicholas Rule, an associate professor of psychology, report on three separate studies that suggest the facial features of successful non-profit CEOs are noticeably different from leaders of for-profit companies.

Power and charity don't mix

For the first study, Re, Rule and team showed images of the faces of many of the CEOs of the 100 highest-revenue non-profit organizations – or NPOs – as listed by Forbes for 2009, 2010 and 2011.

A group of 169 participants were shown closely-cropped black and white photos of CEO faces – but not told they were CEOs – and asked to rate them on dominance, likability, facial maturity, and trustworthiness, as well as leadership, age, attractiveness, and happiness.

The researchers then grouped some of the scores together, combining dominance and facial maturity into a score they called 'power', for example, as well as grouping trustworthiness and likability into a score they labelled 'warmth'.

They found that the non-profit CEO faces that the participants saw as having high 'power' scores tended to have lower total revenue, funding from private sources, and fundraising efficiency for their organizations than non-profits with CEOs that ranked lower on the power index.

"The results were actually much more dramatic than I would have thought," says Re. "Previous studies have shown that CEOs who appear dominant seem to do well when it comes to generating wealth. But for NPOs, we found the opposite."

Sharks vs teddy bears

Re and Rule also had a group of participants look at the faces of CEOs of profit-based businesses. The participants’ scores suggested that the CEOs of successful for-profit companies look more powerful than the CEOs of NPOs.

This seems to support the results of previous studies that have suggested facial cues of power signal real dominance, aggression, and selfishness, and that people who display these facial cues may enjoy greater success as leaders of companies where the main goal is personal gain and stakeholder wealth.

A new view of non-profit leadership

"Even though the most successful CEOs of for-profit businesses might be these cut-throat, intense sharks, that's not necessarily the key to good leadership across-the-board," says Re.

"What we seem to have found is that people who come off as more powerful won't get as far or do as well working at non-profits," says Re. "It's not necessarily that non-profits are picking softer-looking people, it's that such people – perhaps drawn to working for a nobler cause – are likely the ones who have gotten ahead and risen through the ranks throughout their career in the non-profit industry."