UHN researchers were awarded a total of $1.14M from the Canada Foundation for Innovation (CFI) to purchase key research equipment.
The funds were awarded through CFI’s John R. Evans Leaders Fund, which is designed to help institutions attract and retain the best and brightest researchers from around the world.
The funds will enable the acquisition of equipment needed to implement the following research programs:
These projects were among 220 new infrastructure projects announced at Laurentian University in Sudbury, Ontario on August 15, 2017. In total, these investments sum to over $52M distributed across 51 Canadian universities, including $5.7M at the University of Toronto.
Commenting on the announcement, Canada’s Minister of Science Kirsty Duncan said, “Our scientists need the best tools and equipment for ground-breaking research and discovery, and we are committed to ensuring they have them.”
“Their successes will lead to an improved economy and will fuel an active research community here in Canada and internationally.”
Congratulations to the six UHN researchers involved and to CFI for their continued support.
In 2014, actress and singer Selena Gomez took some time out of the spotlight. While rumours swirled, it turned out that the hiatus was required so she could receive treatment for a disease known as lupus.
Millions of individuals worldwide, mostly women between the ages of 15 to 44, struggle with lupus. It is an autoimmune disease, meaning that the body’s immune system goes into overdrive—attacking and causing extensive damage to healthy tissue.
B cells, named for their production in bone marrow, are one of the body’s most important immune cells; they release specialized proteins (ie, antibodies) that protect the body from invaders such as viruses or bacteria. However, it is believed that they also play a critical role in initiating lupus by producing ‘harmful’ antibodies that tell the immune system to attack healthy cells.
Krembil Senior Scientist Dr. Joan Wither and her team have been using experimental models of lupus to uncover how and why B cells betray the body and incite the immune system to attack healthy cells.
In a recent study, the researchers tracked B cell antibody production using an experimental model in which B cells were forced to express a specific genetic code that induced lupus-like symptoms. The team discovered that this genetic code not only increased the proportion of antibody-producing B cells, but also the levels of antibody production.
The code also increased the proportions of another type of immune cell (T follicular helper cell) that is known to enhance the growth of antibody-producing B cells. As the proportion of these T follicular helper cells increased, the proportion of B cells grew, and likewise, antibody production was augmented. These changes created an environment where the immune system was primed to attack healthy tissues.
“Although several studies have shown that defects in B and T cell populations contribute to antibody production, it still is not clear exactly how this occurs in the context of lupus,” says Dr. Wither. “Our data reveal that changes in the proportion of T follicular helper cells may play a role in this process by enhancing the growth of the types of B cells that end up betraying the body and causing lupus.”
This work was supported by the Canadian Institutes of Health Research, and the Toronto General & Western Hospital Foundation.
Chang NH, Manion KP, Loh C, Pau E, Baglaenko Y, Wither JE. Multiple tolerance defects contribute to the breach of B cell tolerance in New Zealand Black chromosome 1 congenic mice. PLoS One. 2017 Jun 19;12(6):e0179506. doi:10.1371/journal.pone.0179506.
The Krembil Research Institute has partnered with The Globe and Mail to release a magazine series highlighting Krembil research advancements. The second magazine in the series was distributed to Globe and Mail subscribers across Canada on June 27, 2017 and focuses on success stories from Krembil’s Donald K. Johnson Eye Institute (read the full issue online).
“In recent years, we’ve assembled a top-notch team of research scientists who are committed to finding answers to fundamental questions about the retina, the brain and disease function,” says Dr. Valerie Wallace, Co-Director of Krembil’s Donald K. Johnson Eye Institute, along with Dr. Robert Devenyi.
Stories within the Globe and Mail ‘Vision’ magazine highlight the significant advancements that Krembil researchers have made in recent years, and the new frontiers that they are exploring to better diagnose diseases of the eye and restore vision. These stories are summarized below:
· Dr. Philippe Monnier is developing therapies that can prevent cell death, reverse nerve damage and cure vision loss, as well as other diseases such as multiple sclerosis and stroke.
· Dr. Efrem Mandelcorn is adapting a simple eye test to facilitate the early diagnosis of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, before people have symptoms.
· Dr. Valerie Wallace is searching for a way to use transplanted cells to restore vision.
· Dr. Robert Devenyi is pioneering a new vision-saving method for people with retinal detachment—an emergency condition in which the tissue layer at the back of the eye is compromised.
· Dr. Jeremy Sivak is looking for ways to treat glaucoma, a group of conditions that are caused by damage to the optic nerve (ie, the major connection between the eye and the brain).
· The late Dr. Martin Steinbach will be remembered for his leading contributions to vision research in Canada, including his most recent scientific endeavour: using virtual reality technology to detect the early signs of glaucoma, before eye damage occurs.
· Dr. Michael Brent is finding ways to break barriers and make it easier for people with diabetes to get regular eye exams.
Also in the magazine, vision research benefactor Donald K. Johnson explains the importance of private sector donations to “…help research organizations go from being good to being great.”
“There are many exciting stories of progress and success emerging from our laboratories,” explains Krembil Director Dr. Donald Weaver. “Some of these stories are told in this magazine. This is only a sampling of what we do and what we are capable of.”
We do it several times a day. We do it quickly. Some people even do it while crossing the street.
Texting is an everyday activity that we do effortlessly and take for granted. However, for a person affected by Parkinson disease (PD), it is challenging and can become impossible.
PD is a progressive neurological disorder characterized by slowed movements, tremors, stiff muscles and impaired balance. Its symptoms are caused by the gradual loss of brain cells, especially those producing the chemical dopamine, which is essential for producing smooth well-controlled movements.
In 2013, a team of researchers led by TGHRI Senior Scientist Dr. Anne Bassett found that PD occurs more frequently in people with 22q11.2 deletion syndrome than those without the syndrome. The syndrome is caused by a genetic alteration that can produce a wide variety of symptoms such as heart and palate abnormalities, learning disabilities, schizophrenia and seizures.
Continuing this thread of work, Dr. Bassett and her colleagues recently examined the signs and symptoms of PD in a group of adults with 22q11.2 deletion syndrome and in healthy participants.
The researchers found that several symptoms of PD—such as slow movements, tremors and reduced balance—were much more common in the 22q11.2 deletion group than in healthy participants. The brain scans from a patient with 22q11.2 deletion syndrome and full-blown PD showed the expected loss of dopamine-producing cells. However, researchers found the opposite in the 22q11.2 deletion group displaying only a few symptoms of PD: these participants had significantly more dopamine-producing brain cells than healthy participants.
“We speculate that too much dopamine, which may be harmful to brain cells, could increase the risk of developing not only PD, but also some of the mental illnesses that commonly occur in 22q11.2 deletion syndrome”, said Dr. Bassett of the findings.
This work demonstrates that studying 22q11.2 deletion syndrome can help to reveal the mechanisms underpinning PD and related movement disorders, as well as other complex brain diseases. Future research will shed light on these mechanisms by studying experimental models and patients over a longer period of time, starting before the appearance of PD symptoms and continuing to full-blown disease.
This work was supported by the Canadian Institutes of Health Research, Brain Canada, the National Commission for Scientific and Technological Research (Chile) and the Toronto General & Western Hospital Foundation. AS Bassett holds a Tier 1 Canada Research Chair in Schizophrenia Genetics and Genomic Disorders. AP Strafella holds a Tier 2 Canada Research Chair in Movement Disorders and Neuroimaging. AE Lang holds the Jack Clark Chair for Parkinson’s Disease Research and the Lily Safra Chair in Movement Disorders at the Toronto Western Hospital. AS Bassett holds the Dalglish Chair in 22q11.2 Deletion Syndrome at the Toronto General Hospital.
Butcher NJ, Marras C, Pondal M, Rusjan P, Boot E, Christopher L, Repetto GM, Fritsch R, Chow EW, Masellis M, Strafella AP, Lang AE, Bassett AS. Neuroimaging and clinical features in adults with a 22q11.2 deletion at risk of Parkinson's disease. Brain. 2017 Mar 24. doi: 10.1093/brain/awx053.
The Krembil Research Institute has embarked on a mission to achieve operational excellence, and focus and augment research activity. As part of this endeavour, Krembil Senior Scientist Dr. Mohit Kapoor has been named as the inaugural Research Director for the arthritis research group.
The mission began with the merging of vision research and clinical programs into one institute, the Donald K. Johnson Eye Institute, under the combined leadership of Co-Directors, Drs. Valerie Wallace and Robert Devenyi. This collaborative effort has already resulted in renewed direction for the vision science research group at Krembil. The next step is to establish research priorities for the arthritis research group.
“It is essential that we establish research priorities that position us for the future,” says Krembil Director Dr. Donald Weaver. “Building harmony between our fundamental and clinical science pursuits will foster collaboration amongst the various medical and surgical disciplines, leading to novel and important research questions, and facilitating the transfer of basic research advancements into clinical practice.”
As part of his new role, Dr. Kapoor has been charged with the task of developing a harmonized strategic research plan (SRP) that will set the arthritis research group’s direction for the next five years, while laying the groundwork for its continued success beyond the next five years. In addition, Dr. Kapoor will be working with the Toronto General & Western Hospital Foundation to help align fundraising priorities with the SRP.
In developing the SRP, Dr. Kapoor will begin an open consultation process with Division Heads, Drs. Aileen Davis (Healthcare Outcomes and Research) and James Eubanks (Genetics & Development); other members of the Krembil Research Council; arthritis research group members, who have active research programs in ankylosing spondylitis, osteoarthritis, pain, psoriatic arthritis, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, and other bone, muscle and joint diseases; and clinical leaders.
“The practice of building and implementing a new research plan is an important one,” stresses Dr. Kapoor. “It provides a framework for what we are trying to build, a world leading biomedical research institute, and reinforces why we are building it—to discover cures and improve our patients’ quality of life.”
Prostate cancer researchers have mapped the impact of an acquired mutation—which is found in about 50% of patient tumour samples—that alters epigenetic identity. The discovery also identifies a new opportunity for targeted therapy.
The findings are published online today in Nature Genetics. The research shows how an acquired mutation involving the fusion of two genes (TMPRSS2 and ERG) can change the epigenetic identity of tumours leading to some genes being turned on while others are turned off, says PM Cancer Centre Senior Scientist Dr. Mathieu Lupien, corresponding author and a member of its Cancer Epigenetics Program—a team focused on breaking the code of cancer.
To learn more about epigenetics in cancer, watch a short video featuring Dr. Lupien, who is also an Associate Professor in the Department of Medical Biophysics, University of Toronto. You can also watch him talk about his current research findings at https://youtu.be/mCDjS-TfS0Q.
The discoveries highlight how mutations can influence epigenetics in prostate tumours and change the identity of cancer cells. Dr. Lupien’s team exploited this fact to identify mechanisms that drive development of fusion-positive prostate cancer.
“Our findings specifically show that fusion-positive prostate cancer is dependent on the NOTCH signalling pathway, which can be blocked chemically in pre-clinical models,” says Dr. Lupien. “This identifies a promising druggable target against fusion-positive prostate cancer and takes us a step closer to providing personalized cancer medicine for up to 50% of prostate cancer patients,” he says.
“We’re hopeful this research can be translated into clinical care in the near future to offer patients an additional, tailored treatment to complement the current standard of care, based on their fusion profile.”
The study team consisted of scientists, pathologists and clinician-scientists involved in the Canadian Prostate Cancer Genome Network (CPC-GENE), the world-leading prostate cancer sequencing program co-led by Dr. Robert Bristow at PM Cancer Centre and Dr. Paul Boutros at the Ontario Institute for Cancer Research.
TMPRSS2-ERG fusion co-opts master transcription factors and activates NOTCH signaling in primary prostate cancer. Kron KJ, Murison A, Zhou S, Huang V, Yamaguchi TN, Shiah YJ, Fraser M, van der Kwast T, Boutros PC, Bristow RG, Lupien M. Nat Genet. 2017 Aug 7. doi: 10.1038/ng.3930.
Supported by the Movember Foundation through Prostate Cancer Canada, the Ontario Institute for Cancer Research funded by the Government of Ontario, and The Princess Margaret Cancer Foundation.
Radiation therapy is an invaluable tool for treating cancer that can help save lives, particularly in childhood cancers. Unfortunately, the treatment itself can cause genetic damage and lead to new tumours that appear decades later.
A team led by PM Cancer Centre Scientist Dr. Gelareh Zadeh and Senior Scientist Dr. Kenneth Aldape studied radiation-induced meningiomas (RIMs)—a type of brain tumour that occurs 10-15 years after radiation therapy for childhood cancer. They looked at the patterns of genetic abnormalities in these tumours and compared them to meningiomas that occur in the general population without prior radiation, called sporadic meningiomas.
They found that RIMs had a distinct genetic profile versus sporadic meningiomas. Nearly all RIMs had losses of chromosomes 1p and 22q, and twelve of the thirty-one tumours studied had particular kinds of mutations in NF2, a gene that helps control cell growth in the brain. None of the naturally occurring tumours had similar NF2 mutations. Furthermore, RIMs lacked mutations that are commonly found in meningiomas.
The findings have implications for survivors of childhood cancer and others who previously received radiation therapy. By providing insight into the type of meningiomas that develop decades after radiation therapy, researchers will be better equipped to identify therapeutic approaches to help these patients.
This work was supported by the MacFeeters-Hamilton Neuro-Oncology Research Program Led by Dr Kenneth Aldape, the Canadian Institutes of Health Research, Adam Coules research grant, the Wilkins Family Chair in Brain Tumor Research and The Princess Margaret Cancer Foundation.
Agnihotri S, Suppiah S, Tonge PD, Jalali S, Danesh A, Bruce JP, Mamatjan Y, Klironomos G, Gonen L, Au K, Mansouri S, Karimi S, Sahm F, von Deimling A, Taylor MD, Laperriere NJ, Pugh TJ, Aldape KD, Zadeh G. Therapeutic radiation for childhood cancer drives structural aberrations of NF2 in meningiomas. Nat Comms. 2016 Aug 4.