CIHR@15 – Canadian Institutes of Health Research Annual Report 2014‑15

From Research to Results – A History of Success

“If we succeed in sustaining and growing this exciting revolution in health research, if we succeed in striking creative global partnerships that will shape and harness this new science to improve health and health care, and if we succeed in diminishing the disparities between those that have access to this new science and those that do not, then we will pass on a better world to our children.”

Dr. Alan Bernstein, Founding President, CIHR

Over the past 15 years, CIHR has supported innovative research in all areas of health. In addition to funding outstanding individuals and teams, we have worked to build capacity in areas where Canada has untapped potential.

For example, CIHR is a proud supporter of programs like the Networks of Centres of Excellence (NCE) and the Centres of Excellence for Commercialization and Research (CECR). The NCEs mobilize Canada’s best research, development and entrepreneurial expertise and focus that expertise on specific issues and strategic areas. The CECRs match clusters of research expertise with the business community, facilitating the development of new products and technologies.

Across the country, researchers are uncovering the roots of disease; empowering communities to tackle health issues; developing devices, medications and other innovative interventions to improve lives; and strengthening the health care system. CIHR is proud to have supported their efforts. Here are just a few of the research success stories that we have helped make possible over the last 15 years.

Discovering how proteins are expressed

Proteins are one of the building blocks of life. Understanding the signals that control how and when proteins are made in the body is crucial to understanding many aspects of human health and disease. Dr. Nahum Sonenberg has made ground-breaking discoveries in this area and, as a result of his work, this field of research has grown enormously.

Dr. Sonenberg discovered that our cells receive signals that speed up or slow down the synthesis of proteins, and that these signals are received by messengers known as “translation initiation factors.” It is from this discovery that we now understand that cancer can develop if there is a problem with the regulation of these messengers. Abnormal regulation of translation initiation factors also plays a role in neurodevelopmental diseases such as autism and the genetic condition known as Fragile-X Syndrome. Dr. Sonenberg also discovered that processes as fundamental as growth, development, and even memory formation are controlled by translation initiation factors.

With the help of funding from CIHR, Dr. Sonenberg continues to build on his earlier research to expand our knowledge of protein synthesis and apply his findings. For example, Dr. Sonenberg’s lab has shown that phosphorylation – a process that switches proteins on or off – plays a role in the development of cancer. By preventing phosphorylation of a translation initiation factor known as eIF4E, his research team was able to slow tumour growth, a finding that could lead to advances in cancer treatment.

Responding to global disease outbreaks

The rate of infections and immune-related diseases has steadily increased since 1980. Over the past 15 years, CIHR has developed collaborations and supported researchers to help prepare our country, and the world, for infectious disease outbreaks.

For example, when SARS hit Toronto in 2003, CIHR moved quickly to fund research to respond to this public health crisis. In 2014, the CIHR Institute of Infection and Immunity (CIHR-III) again moved quickly to launch a clinical trial for an experimental vaccine against the Ebola virus.

CIHR-III has also co-founded the Global Research Collaboration for Infectious Disease Preparedness. This initiative mobilizes funding organizations worldwide to launch a research response within 48 hours of a significant outbreak, thereby saving lives and reducing economic burden.

CIHR has developed collaborations and supported researchers to help prepare for infectious disease outbreaks.

The SARS virus
Credit: CDC/Dr. Fred Murphy; Sylvia Whitfield

Preventing the spread of HIV

Highly active antiretroviral therapy (HAART), the life-saving drug cocktail that HIV-positive patients take, reduces the number of copies of the virus circulating in the patient’s body. As HAART became the standard of care for treating HIV infection, researchers began to wonder if it also reduced a person’s risk of transmitting the virus to someone else.

Dr. Julio Montaner of the B.C. Centre for Excellence in HIV/AIDS was among the first to pioneer this approach to curbing the spread of HIV, now known as Treatment as Prevention® (TasP®). With funding from CIHR, he was able to demonstrate that widespread HAART treatment does slow the spread of the virus.

Jurisdictions that have adopted the TasP® approach include British Columbia, New York City, Washington D.C. and China. In 2014, the World Health Organization fully incorporated the strategy into its guidelines for the use of antiretroviral medications.

Researchers began to wonder if HAART also reduced a person’s risk of transmitting the virus to someone else.

Preventing leukemia from coming back

Not every cancer cell is equal. All cancers contain a mix of cells that vary in terms of their ability to drive tumor growth over the long term and their resistance to therapy.

In 1994, Dr. John Dick’s lab group at the University of Toronto was the first to isolate cancer stem cells in acute myeloid leukemia (AML), which has a very poor survival rate. The researchers have since shown that these rare cells – only about one in a thousand leukemia cells are stem cells – are critical to cancer recurrence. That’s because chemotherapy targets rapidly dividing cells, but cancer stem cells can remain dormant and survive treatment.

In 2006, supported in part by CIHR, Dr. Dick’s lab built on their initial findings to identify a strategy for targeting and eradicating leukemic stem cells in mice. The same year, the researchers also identified stem cells that can initiate colon cancer. Their work may ultimately lead to improved cancer treatments.

A way to create more stem cells

Umbilical cord blood is a promising source of healthy stem cells, which can be used to replace abnormal blood stem cells in patients with diseases such as leukemia. Unfortunately, there are a limited number of usable stem cells found within a single unit of cord blood.

In 2014, Dr. Guy Sauvageau, of the Institute of Research in Immunology and Cancer at the Université de Montréal, led a Canadian team to a major discovery that could allow researchers to dramatically boost the stem cell content of cord blood. Using a molecule known as UM171, Dr. Sauvageau’s team was able to expand the number of cells in a single unit of cord blood as much as tenfold. This discovery, which is now moving into clinical trials, could help provide new treatment options to millions of patients in Canada and around the world.

This promising study was supported by CIHR through the Stem Cell Network, one of the Networks of Centres of Excellence of Canada.

Targeting tumours with viruses

For more than a decade, Dr. John Bell and his colleagues across the country have been working to design and test oncolytic viruses – pathogens that target and kill cancer cells. In 2011, Dr. Bell and clinician scientist Dr. David Kirn became the first to show that an intravenously-delivered viral therapy can consistently infect and spread within tumours without harming normal tissues in humans.

This year, Dr. Bell helped launch the world’s first clinical trial using a combination of two viruses to attack and kill cancer cells and stimulate an anti-cancer immune response. This experimental therapy was developed jointly by Dr. Bell at The Ottawa Hospital, Dr. David Stojdl at the Children’s Hospital of Eastern Ontario and Dr. Brian Lichty at McMaster University.

Over the past 15 years, oncolytic viruses have gone from an interesting laboratory curiosity to clinical testing, with potential to become mainstream cancer therapeutics in the near future.

(L-R) Dr. Brian Lichty, clinician-investigator Dr. Derek Jonker, patient Christina Moniker, Dr. David Stojdl and Dr. John Bell at the 2015 clinical trial announcement in Ottawa

Decoding the breast cancer genome

In a landmark 2009 study, University of British Columbia and BC Cancer Agency researchers Drs. Samuel Aparicio, Marco Marra and Sohrab Shah decoded the DNA sequence of a patient’s metastatic form of breast cancer and followed its evolution over nine years, showing how this complex cancer mutates and spreads. The CIHR-funded study, published in Nature, opens new doors to developing more effective cancer therapies, including personalized treatments targeting the genetic makeup of a patient’s primary and metastatic tumours.

In a 2012 Nature publication, the researchers reported on the genomes of triple-negative breast cancer, which accounts for 25% of breast cancer deaths. Some of the genetic mutations they found have now led to the development of clinical treatments.

Since then, in a 2014 study, they published findings that will provide a map for how certain breast cancers evolve to become drug resistant over time – evidence that could lead to major advances in treatment.

The CIHR-funded study opens new doors to developing more effective cancer therapies, including personalized treatments targeting the genetic makeup of tumours.

Drs. Samuel Aparicio and Marco Marra publish their landmark study of the breast cancer genome

Keeping medical imaging sustainable

In 2009, a temporary shutdown at the Chalk River nuclear reactor led to a worldwide shortage of the radioactive isotope technetium-99m (Tc-99m). This shortage created delays for patients who needed to undergo medical imaging.

In response, the Government of Canada and CIHR reached out to the health research community for alternatives to the Tc-99m currently produced by aging nuclear reactors. Dr. François Bénard, professor of radiology at the University of British Columbia, and his colleagues at TRIUMF, Canada’s national laboratory for particle and nuclear physics, were among the seven teams who took on the challenge.

Dr. Bénard and his team demonstrated that cyclotrons – particle accelerators used to both study and produce subatomic particles – could be used to produce Tc-99m without creating nuclear waste. There are already a number of cyclotrons in use across Canada – many located in hospitals and research labs – that can be adapted to produce Tc-99m in the event of future isotope shortages.

Making premature babies more resilient

Babies born prematurely face many risks as they begin life. Great care must be taken when handling and treating these most fragile patients.

A research team, led by Dr. Shoo Lee of Mount Sinai Hospital, found large variations in the care provided by Canada’s neonatal intensive care units (NICUs) – and large discrepancies in the resulting health and well-being of babies.

In response, Dr. Lee created a national network that allowed hospitals to work together and learn best practices in caring for premature babies. One of those best practices was to involve the parents directly in the care of their baby, as previous research had revealed that premature babies thrive when they are held and nurtured by their parents.

This approach has led to dramatic reductions in infection rates, chronic lung disease, and in the length of NICU stays. It is also saving $7 million annually for Canadian NICUs.

Detecting disease-causing proteins

In a 2003 study, Dr. Neil Cashman of the University of British Columbia greatly advanced our understanding of Creutzfeldt-Jakob disease (CJD), the human form of mad cow disease. Dr. Cashman’s work, funded in part by CIHR, helped confirm that misfolded prion proteins play an important role in triggering CJD, an idea that had been proposed decades earlier.

This landmark finding has opened the door for the development of antibody-based therapies to combat the neurodegenerative disease. Dr. Cashman and his colleagues also went on to demonstrate the role that misfolded proteins play in amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease.

Since these discoveries, Dr. Cashman co-founded Amorfix Life Sciences, now known as ProMIS Neurosciences Inc., a biotech company that is actively developing new tests and treatments for neurodegenerative diseases such as CJD.

Dr. Cashman’s landmark finding has opened the door for the development of antibody-based therapies to combat neurodegenerative diseases.

Brain tissue infected with the prion that causes variant Creutzfeldt-Jakob disease (vCJD)
Credit: CDC/ Teresa Hammett

Studying how gender influences health

Since it was formed, CIHR has made great strides in supporting research that examines sex and gender differences in health.

For example, a 2008 study by Dr. Gillian Hawker and colleagues at the University of Toronto showed that, although women with hip and knee osteoarthritis were more likely to need hip or knee replacement surgery, they were much less likely to have surgery than their male counterparts. In a subsequent study, the researchers showed that when physicians were treating patients with the exact same osteoarthritis symptoms, they were less likely to recommend surgery for a woman than for a man. The end result: fewer women undergo the surgery, which is often the best option for treating pain and restoring joint function in osteoarthritis patients who haven’t responded to other treatments.

Dr. Hawker and her colleagues are now developing criteria to help clinicians determine when joint replacement surgery is appropriate and a patient decision aid that could help overcome bias in treatment.

Connecting environment, genes and health

Researchers have long suspected that early life experiences can have an enduring impact on health and behaviour. But precisely how experiences lead to these changes was unknown.

In a series of studies in the early 2000s, Dr. Michael Meaney and his colleagues showed that the care a rat pup receives from its mother can alter the way some of its genes are expressed, having a long-term impact on how the rat responds to stress. Specifically, rats that receive less care and attention are less able to cope with stress later in life. This landmark study showed that early life experiences could turn certain genes “on” or “off” through “epigenetic” modification of the DNA, thereby explaining how environmental factors could induce long-term changes in gene activity and health.

Dr. Meaney and his colleagues later expanded their research to humans, showing that early life trauma can cause epigenetic changes in peoples’ brains, and that these changes are associated with increased risk of suicide. Dr. Meaney’s research, funded in part by CIHR, has had a revolutionary impact on the “nature vs. nurture” debate, and could dramatically improve our ability to diagnose and treat a wide range of diseases – from mental health issues to cancer.

Keeping seniors balanced

Each year, at least 30% of Canadian seniors experience a fall, with many sustaining serious injuries. In 2005, CIHR’s Institute of Aging launched the Mobility in Aging Initiative to study the mobility issues faced by older Canadians.

The initiative has supported researchers like Dr. Vicky Scott of the University of British Columbia, who developed a falls prevention checklist and action plan for home support workers and seniors themselves. In a 2006 study, Dr. Scott observed a 43% reduction in falls over a six-month period as a result of the checklist. She subsequently developed the Canadian Falls Prevention Curriculum (CFPC) in 2008.

The CFPC is now distributed nationally and internationally through the University of Victoria. More than 4,000 health care providers, community leaders, policy makers and researchers have participated in the program since it was developed.

Changing the way we treat high cholesterol

High levels of “bad” cholesterol are one of the major risk factors for heart disease and stroke. According to Statistics Canada, an estimated 39% of Canadians between the ages of 6 and 79 have unhealthy cholesterol levels. Most of these people are able to manage their condition with lifestyle changes and medications known as statins. But statins aren’t effective for everyone, and they can have negative side effects, such as muscle pain.

New research on the genetic roots of high cholesterol could lead to a whole new approach to treating this condition. In 2003, Dr. Nabil G. Seidah and his colleagues discovered the gene PCSK9, which codes for a protein that plays an important role in maintaining healthy cholesterol levels in the blood. Based on that initial discovery, and with support from CIHR, the pioneering work from Dr. Seidah’s lab led pharmaceutical companies to develop a medication that specifically targets PCSK9 to lower levels of bad cholesterol in the body. The injectable drug is currently in the final stages of clinical trials, and it could represent a major breakthrough in the way we treat high cholesterol.

Improving concussion diagnosis

There is growing awareness about the issue of concussions in children, particularly young athletes. Some children recover completely after experiencing a concussion, but a large number – about one third – suffer symptoms that last more than a month – a condition known as persistent post-concussion symptoms (PPCS). However, until recently, there was no reliable way for clinicians to identify children who are at risk of experiencing PPCS.

Dr. Roger Zemek at the Children’s Hospital of Eastern Ontario, with support from CIHR and the Ontario Neurotrauma Foundation (ONF), recently completed the 5P study: Predicting and Preventing Post-concussive Problems in Pediatrics. It is the largest study to follow children over time to understand the risk factors for PPCS. The findings, which Dr. Zemek presented to the Pediatric Academic Society this year, will give clinicians an evidence-based tool to help them spot children who are likely to develop PPCS, and provide them with the care they need.

Until recently there was no reliable way for clinicians to identify children who are at risk of experiencing PPCS.

Facts and Figures – 2000-2015

The Government of Canada is the largest investor in Canadian health research, with annual funding of approximately $1 billion through CIHR.

Total funding to researchers
2000-01: $370M
2014-15: $960M

Average value of operating grant
2000-01: $92,200
2014-15: $129,266

Number of researchers supported
2000-01: 6,162
2014-15: 13,000

Number of grants and awards
2000-01: 5,585
2014-15: 9,270

CIHR partnerships
2000-01: 49
2014-15: 256

Number of institutions receiving funds from CIHR
2000-01: 69
2014-15: 112

CIHR’s investment in Aboriginal health research
2000-01: $2M
2014-15: $33M

Want to learn more about CIHR-funded research? Visit Health Research in Action, a collection of stories about health research in Canada and how it is improving our lives.

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