Dr. John Dick

14
Jul 2016
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Dr. John Dick

Scientists find genetic switch to increase supply of stem cells from cord blood

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International stem cell scientists, led in Canada by Dr. John Dick and in the Netherlands by Dr. Gerald de Haan, have found the switch to harness the power of cord blood and potentially increase the supply of stem cells for cancer patients needing transplants.…

International stem cell scientists, led in Canada by Dr. John Dick and in the Netherlands by Dr. Gerald de Haan, have found the switch to harness the power of cord blood and potentially increase the supply of stem cells for cancer patients needing transplants.

The findings, published today in Cell Stem Cell, could provide a way to make more stem cells from cord blood, which is increasingly available through public cord blood banking.

“Stem cells are rare in cord blood and often there are not enough present in a typical collection to be useful for human transplantation,” says Dr. Dick, Senior Scientist, Princess Margaret Cancer Centre, University Health Network (UHN), in a media release.

“Our discovery shows a method that could be harnessed over the long term into a clinical therapy and we could take advantage of cord blood being collected in various public banks that are now growing across the country.”

The Dick-de Haan teams found that when a stem cell divides it makes progenitor cells that retain key properties of being able to develop into any one of the 10 mature blood cell types, but they have lost the stem cell’s key ability to self-renew.

Working with mice and human models of blood development, the teams identified microRNA (mirR-125a), a genetic switch that is normally on in stem cells and controls self-renewal, gets switched off in the progenitor cells.

“Our work shows that if we artificially throw the switch on in those downstream cells, we can endow them with stemness and they basically become stem cells and can be maintained over the long term,” says Dr. Dick.

This is just the latest discovery by Dr. Dick. He isolated a human blood stem cell in its purest form and was the first to identify cancer stem cells in leukemia and colon cancer.

Dr. de Haan is Scientific Co-Director, European Institute for the Biology of Ageing, University Medical Centre Groningen, the Netherlands.

Dr. Dick talks about their research at here.

 

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17
Nov 2015
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From right, Will Wang, Caroline Brun, Dr. Michael Rudnicki and Dr. Nicolas Dumont

Canadian reseachers deliver another game-changer

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Within the space of two weeks, two Canadian scientists have unveiled game-changing research into stem cells — providing further proof of Canada’s prominent position in the field.…

Within the space of two weeks, two Canadian scientists have unveiled game-changing research into stem cells — providing further proof of Canada’s prominent position in the field.

On November 5th, the University of Toronto’s Dr. John Dick published a paper in Science that has researchers around the world rethinking how human blood gets made.  Dr. Dick’s team showed that the traditional understanding of blood production is wrong and that stem cells drive production of different kinds of blood cells much earlier than previously thought. This has huge implications for future treatments for blood-based cancers. We blogged about it here.

Yesterday came news that a University of Ottawa team led by Dr. Michael Rudnicki published a paper in Nature Medicine that could completely alter perceptions on how Duchenne muscular dystrophy happens — linking it to intrinsic defects in the function of muscle stem cells.

Affecting about one in about 3,600 boys, Duchenne muscular dystrophy occurs when genetic mutations deplete production of dystrophin protein, causing muscles to deteriorate.

According to an Ottawa Hospital Research Institute release, dystrophin was thought to be a simple structural protein found only in muscle fibres. The Ottawa team discovered that muscle stem cells also express the dystrophin protein. Without it they can produce only one-tenth the number of muscle precursor cells needed to generate functional muscle fibre.

Dr. Nicolas A. Dumont and Yu Xin (Will) Wang are co-lead authors on the paper. that also showed that dystrophin is a key piece of the molecular machinery that enables muscle stem cells to function.

“Muscle stem cells that lack dystrophin cannot tell which way is up and which way is down,” said Dr. Rudnicki. “This is crucial because muscle stem cells need to sense their environment to decide whether to produce more stem cells or to form new muscle fibres. Without this information, muscle stem cells cannot divide properly and cannot properly repair damaged muscle.”

Dr. Rudnicki was featured in many news reports about the discovery, including this feature by CBC.

 

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04
Feb 2015
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‘Cancer is not beyond us’

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Today is World Cancer Day. Under the tagline “Not beyond us,” the campaign’s goal is to raise awareness about the leading cause of death in Canada.…

Today is World Cancer Day. Under the tagline “Not beyond us,” the campaign’s goal is to raise awareness about the leading cause of death in Canada. Cancer is responsible for 30% of all deaths.

This year’s global campaign encourages prevention, early detection, treatment and care. Its message is a simple one: solutions to fight cancer are within our reach.

Stem cells represent a valid treatment option for certain types of blood cancers and solid tumours, and there is hope that more stem cell therapies for cancer will be available in the near future.blood

Canadian scientists are at the forefront of cancer research.  One of the major contributions to the field comes from Dr. John Dick, senior scientist at Princess Margaret Cancer Centre and the McEwen Centre for Regenerative Medicine in Toronto. He was the first to isolate cancer stem cells — in leukemia in 1994 and in colon cancer in 2007. Recently, he and his team found a way to disarm a gene called BMI-1 that regulates colorectal cancer stem cells.

But there is potential to do more. The Canadian Stem Cell Strategy & Action Plan, could lead to novel treatments for cancer. In fact, the goal of the Strategy is for Canada to lead the way in delivering five to 10 safe and effective treatments for chronic diseases within 10 years.

By making stem cell research a national priority Canada has the potential to show that cancer is “not beyond us.”

 

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24
Oct 2014
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Tricky science made simple, part IV

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Back in June, we announced the release of another StemCellShorts video: “What is a cancer stem cell?” narrated by Dr.

Back in June, we announced the release of another StemCellShorts video: “What is a cancer stem cell?” narrated by Dr. John Dick. Stem Cell Shorts is a series of about-a-minute-long informative videos produced by Ben Paylor, a PhD candidate at the University of British Columbia, and Dr. Mike Long, a post-doctoral fellow at the University of Toronto.

Dr. Dick, senior scientist at Princess Margaret Cancer Centre and the McEwen Centre for Regenerative Medicine, was the first to isolate cancer stem cells — in leukemia in 1994 and in colon cancer in 2007. Recently, he and his team found a way to disarm a gene called BMI-1 that regulates colorectal cancer stem cells.

The new video is co-sponsored by the Canadian Stem Cell Foundation and the Stem Cell Network.

All the videos — including “What is a stem cell?” narrated by Dr. Jim Till, “What are embryonic stem cells?” voiced by Dr. Janet Rossant, “What are induced pluripotent stem cells?” narrated by Dr. Mick Bhatia, and “What is a cancer stem cell?” — are now available on the Foundation’s You Tube channel. Click here to view them.

Another instalment, “What is a retinal stem cell?” narrated by Dr. Derek van der Kooy, will be released soon.

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28
Apr 2014
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George Daley Screen Capture

International Panel envisions leading role for Canada in cell therapy boom

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Canada can play a lead role in the coming boom in regenerative medicine and cell therapy technologies, according to an International Expert Advisory Panel.

Canada can play a lead role in the coming boom in regenerative medicine and cell therapy technologies, according to an International Expert Advisory Panel.

Led by Chair Dr. George Q. Daley of Harvard Medical School, pictured at left, the panelists agreed that stem cell research and development is at a major inflection point, and that the next decade will see the arrival of novel disease treatments that will transform patients’ lives and build a new multibillion dollar cell therapy industry.

The Panel, with experts from stem cell research, ethics, and commercialization and the biomedical industry, met in Toronto earlier this spring to review a draft of the Canadian Stem Cell Strategy & Action Plan.

Panelists agreed that Canada is in a strong position thanks to a remarkable record of research excellence, from the discovery of stem cells more than 50 years ago by Drs. Jim Till and Ernest McCulloch to Dr. John Dick’s identification of the cellular origins of leukemia earlier this year.

The Panel also cited Canada’s collaborative, well-trained and well-equipped R&D community and the country’s universal health care system, which can facilitate large-scale clinical trials, as other key factors in driving new therapies to the clinic.

They saw a clear need for developing and implementing a Canadian strategy to capitalize on those strengths and capture the health and economic benefits that to be realized over the next 10 years.

The International Expert Advisory Panel will meet again in Vancouver in June. The Panel’s comments and suggestions — along with those from workshops with health charities organizations, clinicians, researchers, industry leaders and philanthropists — will help shape the final version of the Strategy.

International Expert Advisory Panel Members

George Q. Daley (Chair)

Samuel E. Lux IV Professor of Hematology/Oncology, Harvard Medical School

Director, Stem Cell Transplantation Program, Children’s Hospital Boston

Boston, MA, USA

Alan Bernstein

President & Chief Executive Officer, Canadian Institute for Advanced Research

Founding President, Canadian Institutes of Health Research

Toronto, ON

Gregory Bonfiglio

Founder & Managing Partner, Proteus Venture Partners

Portola Valley, CA, USA

Julia Levy

Co-Founder and former President & CEO and Chief Scientific Officer, QLT Inc.

Vancouver, BC

Geoff MacKay

President and Chief Executive Officer, Organogenesis Inc.

Canton, MA, USA

Chris Mason

Professor of Regenerative Medicine Bioprocessing

Advanced Centre for Biochemical Engineering, University College of London

London, UK

Debra Mathews

Assistant Director for Science Programs, Berman Institute of Bioethics, Johns Hopkins University

Baltimore, MD, USA

Stephen Minger

Global Head, Research & Development for Cell Technologies, GE Healthcare Life Sciences

London, UK

Martin Pera

Professor Stem Cell Sciences, University of Melbourne

Walter and Eliza Hall Institute and The Florey Neurosciences Institute

Program Leader of Stem Cells Australia

Melbourne, VIC, Australia

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24
Apr 2014
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JulieLessard IRIC 2-cropped

Gene that regulates leukemia will take time (and patience) to tame

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While patience is a virtue for most of us, it is an absolute prerequisite for stem cell researchers.

The recent news that scientists have identified a gene called BRG1 that appears to regulate leukemia stem cells marks an important advance in understanding the dread disease.…

While patience is a virtue for most of us, it is an absolute prerequisite for stem cell researchers.

The recent news that scientists have identified a gene called BRG1 that appears to regulate leukemia stem cells marks an important advance in understanding the dread disease. It also signifies years of work by the team led by Dr. Julie Lessard at the Institute for Research in Immunology and Cancer (IRIC) of Université de Montréal.

“About four years,” says Dr. Lessard, pictured left, one of Canada’s leading researchers in the field of hematopoiesis — the art of blood production.

Using mice as subjects, Dr. Lessard’s team found that removing the BRG1 gene left the leukemia stem cells and progenitors unable to survive, divide and make new tumors, permanently shutting down the cancer.  But while they are delighted with their findings, the researchers know they are in for many more years of work.

“We need to identify BRG1 inhibitors that will work in vitro (in test tubes and Petri dishes) and in vivo (with animals and humans),” says Dr. Lessard. “We believe that it is the ATPase activity that is the essential function we need to target for potential drug development, so that’s what we’re going after.”

In essence, that means finding small molecules that can stifle BRG1, the research equivalent to finding a needle in a haystack. Fortunately, IRIC is equipped with computer-driven high throughput screening to search their library of about 120,000 molecules for one that will do the trick. “We are hoping we can get there in the coming years,” she says.

Dr. Lessard’s findings further strengthen Canadian leadership in the field of stem cells and hematopoiesis. It was two Ontario Cancer Institute researchers — Drs. James Till and Ernest McCulloch — who first proved the existence of stem cells in the early 1960s while trying to find new treatments for leukemia. Dr. John Dick, of Toronto’s University Health Network, first identified tumour-initiating cancer stem cells in 1997.

What’s particularly intriguing about Dr. Lessard’s findings is that shutting down the BRG1 gene only appears to affect leukemia-generating stem cells. “Its function in the normal stem cell is rather modest. So you can take the gene out of leukemic cells and it will shut them down without shutting down the other stem cells you need to continue growth.”

While Dr. Lessard is excited about this project, she’s realistic about the amount of time and work involved.

“First of all, we have to have a very solid preclinical product to test in animals.  We think that a therapeutic window must exist. And this is what makes this study more interesting. It will be very exciting to explore in the coming years.”

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13
Feb 2014
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Our gold medal stem cell scientists

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While Canada’s athletes continue to pile up medals at the Winter Olympics in Sochi and prove their prowess on ice and snow, our stem cell scientists are demonstrating that they too are the best in the world.…

While Canada’s athletes continue to pile up medals at the Winter Olympics in Sochi and prove their prowess on ice and snow, our stem cell scientists are demonstrating that they too are the best in the world.

On the same day that 1,000-metre speed skater Denny Morrison came off the bench (courtesy of team mate Gilmore Junio surrendering his spot) to win silver, Dr. John Dick’s team at the University Health Network in Toronto showed the world what the origins of leukemia look like, publishing their findings in the prestigious journal Nature. That news comes hard on the heels of fellow UHN researcher Dr. Gordon Keller’s discovery of a key regulator that controls the formation of blood-forming stem cells, published in the top-tier Cell.

Both papers represent advances in how we understand and may someday treat disease. Without wanting to sound over-the-top patriotic, both prove that, as a nation, we continue to do outstanding work in the field founded by two Canadians — Drs. James Till and Ernest McCulloch — more than 50 years ago.

Essentially, Dr. Dick has identified a “pre-leukemic stem cell” that appears to initiate acute myeloid leukemia (AML) and, because chemotherapy doesn’t eradicate it, allows the disease to come back. Readers of this blog will recall that Dr. Dick was the first in the world to identify cancer stem cells. He proved that just as stem cells produce millions of specialized cells to build and repair tissues and organs (while also renewing themselves), cancer stem cells drive the production of millions of tumour cells (while also replicating themselves).

“What we found is the first normal cell, the cell of origin, that actually sets off the of cascade events, which is going to ultimately lead to leukemia,” Dr. Dick explains in the UHN video above. “So, one of the direct implications and benefits of our findings is that we should be able to detect leukemia before it arises. And, by identifying patients like that earlier, we should be able to follow them and introduce therapy an earlier stage.”

It should be pointed out that this is very early-stage work. To have application in cancer prevention or care, scientists must find a drug that can target a mutation in the gene called DNMT3 that causes these pre-leukemic stem cells to develop. Such a drug would have to be rigorously tested, something that could take years. But it’s still a very important advance.

“What’s John’s given us is something to go after before the disease gets out of hand,” says Dr. Mick Bhatia, Director of the McMaster Cancer and Stem Cell Biology Research Institute. “That’s a huge gift. It’s like stories about the unicorn. He has identified it, now we have to figure out how to capture it. What we have to grapple with is: ‘Are these pre-leukemic cells targetable?’ ‘Can you diagnose them?’ and ‘Can you shut them down before they become leukemic?'”

In his discovery, Dr. Keller, Director of the McEwen Centre for Regenerative Medicine, identified a key regulator controlling the formation of blood-forming stem cells in the early embryo. He focused on retinoic acid, which is produced from vitamin A and is vital in growth. His team demonstrated that the retinoic acid signalling pathway is critical to making blood-forming stem cells. In experiments with mice, the researchers found that blocking the pathway blocked the formation of blood-making stem cells. Activating it pathway set off an upsurge of blood-forming stem cells.

“Our findings have identified a critical regulator for directing pluripotent stem cells to make blood-forming stem cells, bringing us one step closer to our goal of developing a new and unlimited source of these stem cells for transplantation for the treatment of different blood cell diseases,” says Dr. Keller in Medical News Today.

This discovery is also early-stage work, but also very important, says Dr. Bhatia.

“He is capturing a pathway that is critical for when the first blood stem cell is born and how it makes copies of itself — the self-renewal process. That is going to be instrumental in how we move forward clinically.”

While neither finding is a cure for cancer, both are important steps forward on the path to get there. To push the Olympics analogy a bit further, this is like winning a preliminary competition that allows you compete in the medal round.

Except this is not a game and in this medal round, the prize is much more precious than gold.

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09
Dec 2013
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Colorectal cancer advance comes with a challenge

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When Dr. John Dick unveiled his latest cancer discovery last week, he also issued a challenge.

“I think this work will hopefully stimulate (drug) companies to get into the game,” he told the Toronto Star.…

When Dr. John Dick unveiled his latest cancer discovery last week, he also issued a challenge.

“I think this work will hopefully stimulate (drug) companies to get into the game,” he told the Toronto Star.

Dr. Dick, senior scientist at Princess Margaret Cancer Centre and the McEwen Centre for Regenerative Medicine, led a team of scientists and surgeons that found a way to disarm a gene called BMI-1 that regulates colorectal cancer stem cells.

In his own words: “When we blocked the BMI-1 pathway, the (cancer) stem cells were unable to self-renew, which resulted in long-term and irreversible impairment of tumour growth. In other words, the cancer was permanently shut down.”

Some context:  Dr. Dick was the first person in the world to identify cancer stem cells, the evil twin of the stem cell. Just as stem cells spark the creation of millions of specialized cells to repair and regenerate tissues and organs (while also renewing themselves) throughout a lifetime, cancer stem cells drive the production of millions of tumour cells (while also replicating themselves).

Current cancer therapies — essentially, surgery, chemotherapy and radiation — go after the tumour cells but leave the cancer stem cells unscathed. Which is why, researchers believe, cancer often comes back.

When Dr. Dick discovered the cancer stem cell — first in leukemia in 1994 and then in colon cancer in 2007 — he opened up a new front in the war on the dread disease.  With his latest finding, published in Nature Medicine,  he has provided a schematic diagram for building a major new weapon in that war. One that can be aimed at colorectal cancer, the third leading cause of cancer-related deaths in the Western world.

The discovery, which made news across Canada, is based on research conducted with mice. The team replicated human colon cancer in the rodents and identified BMI-1, a gene implicated in other cancers, as the pivotal regulator of the cancer stem cells, driving the cycle of self-renewal, proliferation and cell survival. Then they put an existing small-molecule inhibitor to work blocking BMI-1.

While the implications are enormous, there is a huge chasm to be bridged between working with mice and testing a drug  with people. It could take years and many millions of dollars.  But an important start has been made.

What happens now?

“So the next step … is to find the best possible drug to target this gene,” says Dr. Dick in a University Health Network video. “We’re actually testing a number of drugs that are able to target this gene. We’re trying to determine which is the best one and working with other investigators and other companies to try to develop and optimize the drugs so they can be delivered to patients in the best possible way.”

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