On December 6, 2018, UHN announced the creation of the McEwen Stem Cell Institute (McEwen). With a focus on stem cell research, regenerative medicine and cell therapies, it became UHN’s sixth research institute.
The evolution of this institute, which was formerly known as the McEwen Centre for Regenerative Medicine, signals the progress of the research since the Centre was first eastablished in 2007. In collaboration with research institutions, industry, clinical programs and supporters from around the globe, McEwen investigators will harness stem cell biology to develop treatments for blood cell diseases, diabetes, heart disease and liver disease.
The institute is led by Dr. Gordon Keller and will focus on four areas that have the most potential to benefit patients:
BLOOD Replacing damaged cells in the blood and creating immune-based therapies for cancer (Dr. Keller)
DIABETES Developing ways to regenerate beta cells to treat diabetes and eliminate the need for insulin injections (Dr. Cristina Nostro)
HEART Developing ways to remuscularize and repair the heart (Dr. Michael Laflamme); and creating biological pacemakers to eliminate the need for electronic pacemakers (Dr. Stephanie Protze)
LIVER Creating new liver tissue to repair damaged livers and reduce the need for transplants (Dr. Keller)
“The launch of the McEwen Stem Cell Institute builds on our legacy of innovation in stem cell and regenerative medicine research,” says Dr. Brad Wouters, the Executive Vice President of Science and Research. “The institute will help to usher in entirely new forms of cell-based therapies to tackle some of the most devastating human diseases. It is intensively focused on the creation of new therapies and will become an integral part of the life sciences hub in Toronto.”
PARTNERSHIPS ARE KEY TO RESEARCH INNOVATION
In tandem with the McEwen launch, the cell therapy company BlueRock Therapeutics announced that it is strengthening ongoing strategic collaborations with McEwen researchers.
There are many ways to stand out in a crowd—one way is to look different from those around you.
As cancer progresses, tumour cells develop a number of changes in their DNA that enable them to be more easily detected. One particular type of change to DNA is known as an epigenetic change. Rather than changing the genetic code, epigenetic modifications control how the code is read.
“A major challenge in treating cancer is detecting it early. Finding rare cancer-specific mutations in the blood, especially at earlier stages is difficult,” says Dr. Daniel De Carvalho. “Epigenetic changes, which do not alter the underlying DNA sequence, are not similarly constrained and could provide a new way to detect cancer.”
Dr. De Carvalho and his team took advantage of this phenomenon to develop a blood test that can detect and classify cancer at its earliest stages.
His team profiled thousands of epigenetic changes in multiple cancer types and used the data to predict the presence of cancer DNA in the blood.
They found that epigenetic changes in blood DNA could be used to accurately detect and classify tumours. They have since expanded this research and successfully matched more than 700 tumour and blood samples for a variety of cancer types.
Next steps include testing this method in large studies where blood samples are collected months to years before cancer diagnosis. These studies will help to determine whether the test can be used in the clinic to screen for cancer.
OF FLOWERS AND CANCERS
In nature, the colours that are displayed on flowers’ petals provide an example of epigenetics in action. Despite having the same DNA, epigenetic changes explain why one species of flower can display a variety of different petal colours. Similarly for cancer, epigenetic changes contribute to the characteristics that differentiate tumour cells from normal cells.
Researchers have created a map of the cells in the human liver, revealing the most comprehensive inventory of the different cells that are present in the liver to date.
For the past 20 years, scientists have studied the liver as a mixture of cells. This has made it difficult to fully understand the functions of these cells. To address this issue, Dr. Sonya MacParland and her team used state-of-the-art genetic approaches and software engineering to map out the cells that are present in the liver.
After examining the gene expression profiles of these cells, the team found 20 distinct cell populations, including hepatocytes, endothelial cells, cholangiocytes and various immune cells such as B cells, T cells and natural killer cells. They also discovered two new populations of macrophages.
Dr. Ian McGilvray, a lead scientist in the study explains that, “Until this study, very little was known about the liver macrophage—the ‘tank’ of the immune system that destroys foreign substances and co-ordinates the immune response. We found that there are two distinct populations of macrophages in the human liver, one increases inflammation while the other decreases it. This type of insight has only been made possible by recent transformative advances in experimental and computational methods.”
This map is just the beginning. The team plans to undertake future studies to compare data from healthy liver cells to diseased liver cells, providing further insight into liver biology and disease.
WHAT DOES IT TAKE TO GET A CLEAR PICTURE OF THE LIVER?
From the ancient maps that depicted the continents to the maps that we now use to navigate through traffic, humans have used cartography to define their environments for centuries.
This project advanced the art of mapmaking by providing a detailed map of each cell type present in the liver. It examined over 8,000 individual cells and involved over 30 multidisciplinary experts, including transplant surgeons, immunologists, hepatologists, regenerative medicine scientists, computer scientists and genomics researchers.
These comprehensive results will form part of a larger project known as the Human Cell Atlas, which was created with the aim of defining every type of cell in the human body.
MacParland SA, et al. Nat Commun. 2018 Oct 22;9(1):4383. Supported by the Canada First Research Excellence Fund (Medicine by Design), UHN’s Transplant Program and the Toronto General & Western Hospital Foundation. G Keller holds a Tier 1 Canada Research Chair (CRC) in Embryonic Stem Cell Biology; JE Fish holds a Tier 2 CRC in Vascular Cell and Molecular Biology; and MD Wilson holds a Tier 2 CRC in Comparative Genomics.
Most people breathe spontaneously, without difficulty or concern. However, for those with a traumatic spinal cord injury (SCI), it can be a constant struggle.
Traumatic SCI occurs when the nerve tissue in the spine is damaged by a severe blow to the back or neck, which is most commonly sustained during a motor vehicle accident or a fall. If the damage occurs in the neck area, it can impair the function of—even paralyze—the muscles that control breathing.
As a consequence of their dysfunctional breathing, many patients with SCI in the neck area must be intubated and placed on a ventilator within the first five days after their injury. Breathing-related complications such as lung infections and lung failure account for 80% of deaths associated with SCI in the neck area.
A team of researchers led by Dr. Michael Fehlings has made a discovery that inspires new hope for SCI patients with dysfunctional breathing.
The researchers identified a distinct type of cell in the spinal cord that, when stimulated, increases breathing. These cells are known as cervical excitatory neurons and do not appear to be required for normal breathing.
Importantly, the researchers also showed that stimulating these cells can promote breathing immediately after SCI, when the risk of death is the highest. “Our results have created a lot of excitement in the field,” says Dr. Fehlings. “They are enabling us to develop strategies that could help keep individuals alive by promoting their breathing after spinal cord injury.”
GREAT PLACES ATTRACT GREAT PEOPLE
Talented students and fellows come to UHN to further their research training. Afterwards, many go on to lead their own research groups and make new discoveries. This holds true for the two trainees who led Dr. Fehlings’s study.
Dr. Gordon Keller has been selected to receive the 2019 Ogawa-Yamanaka Stem Cell Prize for his research on pluripotent stem cells.
He has been instrumental in developing ways to coax these cells to differentiate into therapeutically relevant cells, such as cardiomyocytes, hematopoietic cells and liver cells. He has also leveraged this work to develop new applications for regenerative therapeutics, drug testing and disease modelling.
“It is a privilege and honor to receive the distinguished Ogawa-Yamanaka prize for my work on the directed differentiation of pluripotent stem cells,” said Dr. Keller.
“I am fortunate to have had the opportunity to work in the field of stem cell biology for most of my career and to contribute to the translation of this science to the development of new therapies to treat human disease.”
Dr. Keller was selected from a pool of highly competitive international candidates by a committee of leading stem cell experts. The award and prize valued at $150,000 will be presented to him at a ceremony in November 2019 at the Gladstone Institutes in San Francisco, California. As part of the event, he will present a lecture, which will be streamed live. To register to watch, click here.
Dr. Keller is the director of University Health Network’s McEwen Stem Cell Institute and a Senior Scientist at the Princess Margaret Cancer Centre. He is also a professor in the Department of Medical Biophysics at the University of Toronto and scientific co-founder of BlueRock Therapeutics Inc.
Congratulations Dr. Keller!
Source: Gladstone News
If every picture tells a story, then two pictures have the potential to tell a more complete story.
This appears to be true when two very different types of medical images—computed tomography (CT) and positron-emission tomography (PET) scans—are superimposed to help diagnose cancer.
While a CT scan provides information about the location of and structure of a tumour, a PET scan can visualize fast-growing cancerous cells. Combined, the two images can create a more accurate snapshot of the location and severity of a patient’s cancer—characteristics that are used by physicians to determine the ‘stage’ of a cancer.
Dr. Ur Metser recently led a study that provided the most conclusive evidence to date that PET and CT are a powerful combination for staging lymphoma—a common type of blood cancer. The study was performed in collaboration with Cancer Care Ontario and cancer centres throughout southern Ontario.
He compared the effect of using combined PET/CT to that of CT alone at diagnosis on the management and outcomes of 850 Ontarians with lymphoma.
The researchers found that combined PET/CT enabled the detection of advanced disease in 18% more patients than CT alone and changed treatment plans for 40% of patients. Importantly, PET/CT was linked to improved survival in patients with aggressive non-Hodgkin lymphoma.
“In this study, we show that combined PET/CT enables doctors to more accurately stage lymphomas at diagnosis and thus design effective treatment plans,” says Dr. Metser. “Our findings also suggest that the use of combined PET/CT to inform disease management for certain lymphomas can lead to improved patient survival.”
IMPROVING CLINICAL CARE THROUGH RESEARCH
While the use of combined PET/CT for staging lymphomas was recommended by an international committee of experts in 2013, little prospective evidence existed to support the need for the extra PET scan at the time.
Welcome to the latest issue of Research Spotlight.
As Canada’s largest research hospital, UHN is a national and international source for discovery, education and patient care. This newsletter highlights top research advancements across UHN and from over 1000 researchers appointed at our institutes.
Stories in this month’s issue:
● Changing Practice: Study finds not all cervical cancer should be treated with minimally invasive surgery
● Leaving Their Mark on the Brain: Repeated concussions in former athletes linked to high levels of tau protein.
● Sweetening the Pill: New pill found to be safe for use in diabetes patients as an alternative to injection.
● A Partnership to Make New Medicines: MaRS Innovation launches new drug discovery program based on UHN discovery.
Read these stories and more online here. To read previous issues, see the newsletter archive.
Research conducted at UHN's research institutes spans the full spectrum of diseases and disciplines, including cancer, cardiovascular sciences, transplantation, neural and sensory sciences, musculoskeletal health, rehabilitation sciences, and community and population health.
Learn more about our institutes by clicking below:
