Faculty of Medicine Research Report 2011-2012

University of Calgary

Faculty of Medicine Research Report 2011-2012

Editor Kathryn Sloniowski Contributors Colleen Biondi Marta Cyperling Amy Dowd Todd O’Keefe Leora Rabatach Kathryn Sloniowski Photography Carlos Amat Chris Kindratsky Trudie Lee Andy Nichols Bruce Perrault Laurie Wang Creative Design Wilma Olivier-Walden Imagine, University of Calgary

Thank you to all institute and centre staff for their contributions

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FACULT Y OF MEDICINE Research Report 2011-2012

2011-2012 Research Report

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Message from the Senior Associate Dean (Research) Hotchkiss Brain Institute Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases Libin Cardiovascular Institute of Alberta Alberta Children’s Hospital Research Institute for Child and Maternal Health McCaig Institute for Bone and Joint Health Southern Alberta Cancer Research Institute Institute for Public Health Centre for Advanced Technologies Calgary Centre for Clinical Research Graduate Science Education Chairs and Professorships Financial Statements 2010-2011

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Bringing our research from bench to bedside Each year as we create the Faculty of Medicine’s annual research report, I have the opportunity to reflect on our accomplishments. I have been delighted with the calibre of work we consistently produce and 2011 is no exception−we have numerous achievements of which we are very proud.

First, Paul Kubes, PhD, was honoured with the top award for medical research given by the Canadian Institutes of Health Research−Canada’s Health Researcher of the Year. Paul is Director of the Snyder Institute and his personal research−focused on infection and inflammation−leads the world. The faculty is very proud to have Paul as a member.

Another milestone of 2011 was the inauguration for the Institute for Public Health. This is the seventh institute in the Faculty of Medicine and brings to fruition the first stage of the transformational project, first launched in 2009, to create an institute-based, multidisciplinary and translational research enterprise. Brief overviews of the research activities of all our institutes are to be found in the pages that follow.

Beyond these, we have numerous noteworthy achievements this past year, ranging across the full spectrum of biomedical research from basic science, to cohort studies, to clinical trials. For this edition of our annual report I chose to focus on our research to improve patient care and health service delivery. You will find many examples in the following pages. For instance, Dr. Shelagh Coutts discovered a way to use easily accessible technology, often found in rural centres, to predict the likelihood of a second, severe stroke in individuals who have experienced a minor stroke. Because of Shelagh’s research, more patients will be safely discharged from hospital to recover at home, thereby reducing the strain on our health-care system. Suzanne Tough, PhD, has launched an ambitious research program involving one of the largest pregnancy and birth cohort studies in Canada, which will follow 3,300 mother-baby pairs for three years following birth, to better understand birth outcomes and women’s experiences during pregnancy. Dr. Derek Exner is leading an international study to determine if a small implantable defibrillator can reduce deaths due to sudden cardiac arrest. Derek’s study is the largest clinical trial ever run out of the Faculty of Medicine and has received $16.8-million for the pilot phase.

These achievements and initiatives, as well as many, many others, are the result of broad collaborations on many fronts, including with the federal and provincial governments, Alberta Health Services, other faculties in the University of Calgary, our industrial partners, and numerous volunteers in the community who have given generously of their time and support. As ever, we remain exceedingly grateful for the ongoing financial support of all of our donors and funders− without their generosity and commitment to creating the future of health we would not have had much of the success we so consistently enjoy. Similarly, I would like to extend our thanks to all the foundations that have supported our researchers during this past year.

Finally, I would like to acknowledge the leadership of our dean, Dr. Tom Feasby, who is completing his five-year term of office at the end of June, and the myriad contributions he has made to research in the Faculty of Medicine. Tom’s support and encouragement has propelled our research on multiple fronts, and it is because of his leadership that we are where we are today−consistently able to translate imagination, innovation and discovery to improve lives in our community and beyond.

Richard Hawkes, PhD Senior Associate Dean (Research) Faculty of Medicine

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Hotchkiss Brain Institute Samuel Weiss, PhD, director

Institute overview The University of Calgary’s Hotchkiss Brain Institute (HBI) is a leading centre for neurological and mental health research, education and innovation. In the HBI, basic neuroscientists contribute to solving clinical problems while they continue to make fundamental discoveries that change our understanding of the brain and nervous system.

Clinical researchers and population health specialists help to define the neurological and psychiatric problems that are pursued collectively throughout our priority areas of foundational and translational investigation.

The HBI consists of more than 150 full and associate members, and close to 200 of the best and brightest trainees who are dedicated to advancing neurological and mental health research and education. With a “bench to bedside” research model at the forefront of the HBI’s mission, our discoveries in the laboratory can be quickly and effectively translated into clinical practice. Ultimately, research and investigation at the HBI means improved lives and health for our community.

Our members work collaboratively within three foundational research themes: axon biology and regeneration, cerebral circulation, and neural systems and behaviour; and four corresponding translational research programs: multiple sclerosis, spinal cord and nerve injury, stroke and vascular dementia, and depression and psychosis. Within these priority research areas, 2011 has marked a year of innovation, discovery and excellence. From discoveries into the biological basis of why stress is a contributor to obesity, to advances in stroke and multiple sclerosis care, each of the HBI’s priority research areas represents strength and emerging potential in research, education and the translation of discoveries into improved health.

A large part of the HBI’s success is due to the outstanding efforts and contributions of its talented investigators.

Our researchers continue to achieve excellence through securing publications in top journals−obtaining research grant funding and receiving prestigious honours. In 2011, one of our country’s highest civilian honours, the Order of Canada, was awarded to HBI researcher Dr. Garnette Sutherland. Our trainees, working with HBI members, represent the future of neurological and mental health research and will continue to shape the success of the HBI, helping to maintain the institute as a leader in neuroscience research, education and innovation.

Multiple sclerosis research receives large grant A study led Dr. Peter Stys, a member of the Faculty of Medicine’s Hotchkiss Brain Institute (HBI), which also includes fellow HBI members V. Wee Yong, PhD, and Jan van Minnen, PhD, is investigating the complex interplay between degeneration and inflammation in multiple sclerosis (MS). The study received a $3.8-million grant from the Multiple Sclerosis Society of Canada and the Multiple Sclerosis Scientific Research Foundation in November 2011.

To date, researchers have largely attributed central nervous system (CNS) damage in MS to an autoimmune attack in which inflammation causes the hallmark patches of demyelination (also called plaques or lesions).

“This study hypothesizes that the inflammatory response in MS is the result of an underlying degenerative process rather than the primary cause of injury,” says Stys. “In other words, an underlying mechanism causes degeneration that prompts the inflammatory process, which in turn causes more degeneration.”

In general, progressive disease is characterized by a non-inflammatory neurodegenerative process.

Approximately 10 per cent of people with MS are diagnosed with primary progressive MS. A more common type of progressive MS is secondary progressive MS, which begins as relapsing remitting MS, but then transitions to a progressive course. Fifty per cent of those with an initial diagnosis of relapsing MS eventually develop secondary progressive MS within 10 years of diagnosis.

Currently in Canada there are seven disease-modifying treatments approved for relapsing forms of MS. However, despite best efforts, little progress has been made to date in the disease management of primary progressive MS or secondary progressive MS without relapses.

“The important roles of autoimmunity and the damage of inflammation are undeniable. But this doesn’t mean that this is the starting point. If we can understand more about the earliest triggers in the disease processes in MS, we might learn how to intervene and prevent the damage that occurs prior to an inflammatory response,” says Stys. “This research could provide information that benefits both relapsing remitting and progressive forms of MS.” Dr. Peter Stys and V. Wee Yong, PhD, are supported

by Alberta Innovates – Health Solutions.

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Predicting recurrent stroke risk When treating stroke patients, doctors can use a magnetic resonance imaging scan (MRI) of the brain to predict if a patient who has suffered a minor stroke, or transient ischemic attack (TIA), and has neurological symptoms such as weakness or speech issues, is at high risk for a recurrent stroke. Unfortunately, MRI machines are not always immediately available.

In a recent study lead by Dr. Shelagh Coutts, a member of the Faculty of Medicine’s Hotchkiss Brain Institute (HBI), researchers discovered that computerized tomography (CT) scans, which are generally easier to access than MRIs and can be found in most medical centres including rural hospitals, can help doctors predict the risk of a second stroke in patients who have experienced a TIA. By predicting stroke risk, doctors can decide if stronger medications should be used to prevent future episodes, or if a patient can be safely sent home− thereby reducing strain on the health-care system and the patient.

“Many physicians may not have access to an MRI

machine to see what is happening in the brain,” says Coutts. “Therefore, this study could allow medical interventions to be more widely available rather than in just the specialised centres that have access to MRI. Even in centres that have MRI machines, there are often delays in getting patients into a scan.”

In order to assess stroke risk, Coutts and her colleagues used an injection of dye that can easily be administered as part of a routine CT scan−called a CT angiogram−to visualize the blood vessels from the heart to the brain.

The researchers found that patients who had evidence of blockages or narrowed vessels on their CT scans were at high risk for a recurrent stroke. Further, they found that the CT angiogram scan was able to predict the recurrence of stroke with the same accuracy as an MRI. “This research has an immediate impact and lets us use readily accessible tools to help patients,” she says.

Dr. Shelagh Coutts is supported by Alberta Innovates – Health Solutions and is a recipient of the Heart and Stroke Foundation of Canada’s Distinguished Clinician Scientist Award.

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Dr. Shelagh Coutts (right) speaks with a stroke patient.

According to the Heart and Stroke Foundation, each year, approximately 15,000 people in Canada will experience a transient ischemic attack, many of which go unreported.

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Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases Paul Kubes, PhD, director

Institute Overview The diversity of its world-class researchers enables the University of Calgary’s recently renamed, Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases to understand and attack chronic diseases from every angle. Its members are leading the fight against a host of serious health problems including sepsis, MRSA, cystic fibrosis, type 1 diabetes, inflammatory bowel disease, and chronic obstructive pulmonary disease.

The Snyder Institute’s research is led by world-class scientists and clinicians driven to end the war on chronic diseases. Our discoveries push clinical practices into research and research into clinical practices, facilitating our core belief that research isn’t just about the discoveries but about the impact on individual lives.

It is through our multi-disciplinary research that our discoveries both extend and improve the quality of life of those afflicted by chronic disease.

The Snyder Institute has benefitted greatly from all of the many partnerships we have established with private and public donors, non-profit organizations and corporate sponsors. It is because of these partnerships that we have attracted a number of high-quality new recruits, and have been able to create a new benchmark in research infrastructure.

We are particularly proud of our Live Cell Imaging Facility that is capable of imaging all aspects of the immune response, as well as infections in the brain, liver, skin, muscle and other organs. The University of Calgary and the Faculty of Medicine have recently invested $2.4-million for renovations, which will leverage it to be one of the leading facilities of its kind in the world.

This past year, the Snyder Institute’s research has been recognized on multiple fronts highlighting our dedication to ending the war on chronic diseases. Three of our

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multi-disciplinary teams of clinicians and researchers received team grants from Alberta Innovates — Health Solutions (AIHS), demonstrating our advanced undertakings through research: Alberta Sepsis Network (ASN) A team of over 25 researchers and clinicians from the Universities of Calgary, Alberta and Lethbridge, whose underlying goal is to change the paradigm of diagnosis and treatment of sepsis in critically-ill patients.

Inflammatory Bowel Disease (IBD) Consortium By combining the expertise from a number of faculties and integrating clinical, population-level and basic science research, the team hopes to find the answers to Crohn’s disease and ulcerative colitis that have eluded scientists for decades.

Vaccine Design and Implementation (VDI) The overall goal of the VDI is to work on developing an approach to the prevention of childhood infections caused by host-restricted, bacterial respiratory pathogens.

In addition to these team grants, the Snyder Institute’s Director Paul Kubes, PhD, received one of the top awards in medical research when he was named Health Researcher of the Year by the Canadian Institutes of Health Research (CIHR). The award is accompanied by a $500,000 research grant which he will use to continue his research in infection and inflammation−conditions which affect a vast number of individuals.

Another one of our researchers, Dr. Pere Santamaria, received grants from CHRP, NSERC and CIHR, totaling $570,480, to support his work on immunology.

Santamaria’s research has shown promising results in the treatment and prevention of type 1 diabetes.

Inflammatory bowel disease affects approximately 170,000 Canadians.

Understanding inflammatory bowel disease Dr. Gilaad Kaplan, a member of the Faculty of Medicine’s Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, believes inflammatory bowel disease (IBD) is a chronic disease that is potentially debilitating for the young and old alike. IBD is an improper immune response to the bowel, which can lead to symptoms such as stomach pain, bleeding and diarrhea. Those with the condition also require continuous medication and face the possibility of surgery. Kaplan, who was named one of Calgary’s Top 40 Under 40 by Avenue Magazine, states that the major impact of IBD is how the burden of the disease interferes with the patient’s quality of life.

As the disease predominately affects young individuals for life, it can impact important life events such as postsecondary studies, personal relationships and careers.

As a clinical gastroenterologist with a research interest in Crohn’s disease and ulcerative colitis, Kaplan has a frontline perspective with patients who suffer from IBD. “This disease is predominantly diagnosed in early adolescence and there is no cure. It has a huge impact on them,” he says. “It also has a significant impact on society in terms of health-care implications, with an estimated $700-million in direct health-care costs in Canada. It has inspired and motivated me to think about the underlying causes of the diseases and translate it into better ways to treat and eventually find a cure.”

Kaplan recognizes that although IBD is a common disease in industrialized countries, such as Canada and the United States, it is also emerging in countries such as China and India. From this observation, it is known that genetics alone do not account for IBD−there must be external factors that interplay with a patient’s molecular fingerprint, such as air pollution.

As a member of the Alberta Innovates — Health Solutions (AIHS) funded Alberta IBD Consortium, Kaplan is one of many Snyder Institute members actively studying the external factors underlying IBD. “An important component of this group is characterizing patients with IBD. By compiling extensive chart reviews, environmental risk factors and genetic susceptibility, we hope to define a personalized clinical picture of these patients,” he says. “Blood and tissue is also bio-banked, allowing other researchers to use these specimens in their own work.”

Stroke discovery made After experiencing a stroke, the brain tries to protect itself by blocking inflammation. In the process, the patient becomes highly susceptible to infection, which could potentially lead to severe illness and even death.

Researchers at the Faculty of Medicine’s Snyder Institute for Chronic Diseases have recently discovered the mechanism behind this response, and how to treat it. The study was recently published in the journal Science.

Using a mouse model, researchers discovered that Natural Killer T-cells (NKT) are the immune cells activated in a patient after a stroke. These cells suppress the immune system as the body tries to prevent inflammation in order to protect the brain.

“When we discovered that these novel NKT cells are important in fighting infection in stroke, we were able to specifically target them,” says Paul Kubes, PhD, senior author of the study and director of the Snyder Institute.

The researchers have also found a new drug that can stop the NKT cells from acting on the immune system, and consequently, prevent infections.

“This means infections can be controlled without having to administer high levels of antibiotics,” says Kubes. “This in its own right is important. We need to avoid excessive use of antibiotics because it can lead to the development of antibiotic-resistant strains of bacteria.”

Early indications are that NKT cells in humans behave very similarly to NKT cells in mice, making this information highly relevant to human stroke.

“The research does not cure the stroke itself,” says Connie Wong, PhD, a co-author of the study and member of the Snyder Institute. “But by providing novel therapies, it holds the promise to significantly decrease death rates associated with stroke.”

Paul Kubes’ research is supported by Alberta Innovates – Health Solutions and the Canadian Institutes of Health Research.

Kaplan recognizes that the core strength of the Snyder Institute is its interdisciplinary team of integrated scientists, spanning the continuum of bench to bedside and equaling a formula for success. Its support, infrastructure and people will all play key roles in a toplevel approach to understanding the needs of chronic diseases.

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Dr. Gilaad Kaplan

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Libin Cardiovascular Institute of Alberta Dr. Todd Anderson, director

Institute Overview

Drug mechanism discovered

On March 6, 2003 the Alvin and Mona Libin Foundation presented one of the largest one-time donations to the Calgary Health Region and the University of Calgary.

The gift was $15 million, and the Libin Cardiovascular Institute of Alberta was born, giving Calgary a worldclass institute for heart health research, education, and patient care. The Memorandum of Understanding, formally establishing the institute, was signed by the University of Calgary, Calgary Health Region (now Alberta Health Services), and the Alvin and Mona Libin Foundation on January 27, 2004.

Carvedilol is an FDA approved drug that has been used for years to treat patients suffering from heart arrhythmias; however, how exactly the drug treats the condition has never previously been fully understood.

The vision of the Libin Cardiovascular Institute of Alberta is to provide a superb, efficient, integrated program of cardiovascular wellness, health care, research and education. The institute’s strengths include:  Providing superb education and training of tomorrow’s health-care professionals, including physicians, surgeons, researchers, nursing and technological staff.  Development of an outstanding cardiovascular health promotion and disease prevention program, which will educate and serve the population of southern Alberta.  Increased access to cardiac services through innovative use of technology such as telehealth.  Providing world-class treatment, using state-of-the-art technology and equipment for patients from southern Alberta, British Columbia and Saskatchewan.  Increasing personnel and capacity of facilities to better meet the needs of the patient population.  Fortifying cardiovascular basic science, clinical science, population health research, and the relationships among them.  Making resources and leadership available to achieve these goals, and to foster the integration of cardiovascular wellness, health care, research and education.

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The Faculty of Medicine’s Wayne Chen, PhD, a member of the Libin Cardiovascular Institute of Alberta, was the principal author of a study that discovered the mechanism responsible for this treatment is the drug’s ability to suppress spontaneous calcium waves. The study was a collaborative effort between Chen and 28 other researchers, and was recently published in the journal Nature Medicine. Along with the discovery comes the opportunity to develop new drugs to treat patients with arrhythmias.

While a number of factors can cause arrhythmias, or irregular heartbeat, the spontaneous release of calcium by the heart muscles is one cause. Calcium is necessary for a continuous and steady heartbeat−with each beat of the heart, calcium is released, inducing the subsequent beat. When calcium is spontaneously released between heartbeats, the regular rhythm of the heart is disrupted, resulting in an arrhythmia. A heart with an arrhythmic beat is unable to pump blood through the body at the desired rate, resulting in patient symptoms such as weakness, fatigue, palpitations and, in some cases, death.

Chen says that on the basis of this finding, he and his team are interested in potential modifications to carvedilol. “This is a significant step towards the development of new and more effective anti-arrhythmic drugs,” he says.

Dr. Anne Gillis, also a member of the Libin Institute and one of the study’s co-authors, says the discovery could have an immediate clinical benefit and allow cardiologists to prescribe the drug off label for another heart irregularity−a rare genetic condition known as catecholaminergic polymorphic ventricular tachycardia (CPVT).

Wayne Chen, PhD, is supported by Alberta Innovates - Health Solutions

Sudden cardiac arrest is a sudden loss of heart function and is not a heart attack. A heart attack is caused by a blocked vessel resulting in a loss of blood supply to part of the heart.

Study aims to reduce deaths caused by sudden cardiac arrest Sudden cardiac arrest accounts for up to 50,000 deaths in Canada each year, and Dr. Derek Exner is leading a new international study in hopes of determining if a small implantable cardioverter defribrillator (ICD) can reduce those numbers.

“This study may change how we manage patients after a heart attack and has the potential to save thousands of lives each and every year,” says Exner, who is a member of the Faculty of Medicine’s Libin Cardiovascular Institute of Alberta.

The study is based on Exner’s past research in the REFINE study, where a new method was developed that identified patients at high risk of serious heart rhythm problems following a heart attack. With approximately $16.8-million supporting the pilot phase of the program, the Libin Cardiovascular Institute is serving as the Clinical Coordinating Centre and will be collecting patient data from 16 sites in Canada, the United States, and Europe.

ICDs have been proven to be highly effective in treating rapid ventricular arrhythmias, and are presently used to

prevent death in patients with very poor heart function or who have survived a life-threatening heart rhythm problem. However, this new study will focus on a different cohort of patients−patients with at least a minor reduction in heart function after a heart attack, plus additional criteria identified in the REFINE study. This cohort represents a large percentage of those who die suddenly each year, although ICD therapy is not currently available to them as a treatment option.

The pilot phase of the study has an anticipated duration of 18 months. If it’s shown to be feasible in terms of study enrolment and site activation, the study will expand to include up to 75 sites, with investments potentially reaching over $40-million. Approximately 10,000 patients could be screened−1,400 of whom will be enroled in the study. Of those enroled, patients will be equally assigned or randomized to receive either conventional care including medication and lifestyle modification, or conventional care plus an ICD. “Research to identify those at risk and methods to prevent death from heart rhythm problems are vital,” says Exner. “It is an honour to be leading such an important study.”

Dr. Derek Exner is supported by Alberta Innovates – Health Solutions.

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Dr. Derek Exner

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Alberta Children’s Hospital Research Institute for Child and Maternal Health Dr. R. Brent Scott, director

Institute Overview The Alberta Children’s Hospital Reserach Institute for Child and Maternal Health (ACHRI) is a multi-disciplinary partnership institute of Alberta Health Services, the Alberta Children’s Hospital Foundation, and the University of Calgary. Membership encompasses the faculties of arts, engineering, medicine, veterinary medicine, nursing, kinesiology, science, and social work.

ACHRI’s research strategic plan is predicated upon the knowledge that circumstances during conception, embryogenesis, fetal, child and youth development are predictive of, and create the foundations for, adult health.

Our members’ interdisciplinary research programs are focused on the discovery and application of knowledge that can optimize the transitions from conception to adulthood, and in so doing, contribute to improved health outcomes throughout one’s entire life.

Researchers in ACHRI are organized into three themes:  Behaviour and the Developing Brain  Healthy Living and Optimizing Health Outcomes  Molecular and Genetic Basis of Child and Maternal Health In support of the three themes, six research platforms have been identified for investment and development: Functional Imaging

The capacity for high resolution functional imaging in children is being enhanced with the installation of a 3T fMRI at the Alberta Children’s Hospital (ACH), and recruitment of research physicists will support ongoing research in child imaging, developmental pediatrics, child behaviour, youth mental health, neurology and neurosurgery (specifically epilepsy and epilepsy surgery and neuro-oncology).

Clinical, Population and Health Services Research Infrastructure

Clinical, population health and health service delivery research supports (space, personnel and equipment) will be enhanced to facilitate the design and operation of clinical trials (data collection, data entry, database management, data interpretation, sample collection and storage) with research coordinator, epidemiology, bioinformatic, biostatistical, health economics, knowledge translation, pharmacy and mentorship skills.

Basic and Applied Human Genetics

ACHRI is investing $5-million over five years to support the initial acquisition and operation of next generation DNA sequencing technology and bioinformatic support for research activities in the Molecular and Genetic Basis of Development theme. The intent is to facilitate the development of provincial human genomics research capacity and the recruitment of high quality personnel in basic and applied genetic research and bioinformatics.

Experimental and Applied Therapeutics

Under the umbrella of a $40-million Childhood Cancer Collaborative, ACHRI is partnering with Alberta Health Services and the Southern Alberta Cancer Research Institute to invest $10-million in new drug screening, pre-clinical anti-tumor testing in cell lines and animal model systems, and human clinical trials, leveraging our current participation in P.O.E.T.I.C.−an international network of prominent cancer research hospitals collaborating around Phase 1 clinical trials.

Education–Training the Next Generation of Child and Maternal Health Researchers

The institute is planning expansion of the support for graduate and post-graduate trainees in its themes.

Institute Research Space

In the future, as ACHRI’s research programs grow in size, they will outgrow our current infrastructure (space, equipment, programs, people and partnerships). Multiple options aligning with University of Calgary opportunities and priorities are being pursued.

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ACHRI’s primary function is to establish and sustain an optimal research environment, with particular emphasis on the fundamental infrastructure (space, equipment and people) that enables institute success.

Investigating preterm labour Donna Slater, PhD, a member of the Faculty of Medicine’s Alberta Children’s Hospital Research Institute for Child and Maternal Health (ACHRI), has been studying one of the most complex puzzles associated with human pregnancy: preterm labour.

Approximately 10 per cent of pregnant women experience this condition, which is defined as labour before 37 weeks of gestation. Babies born prematurely are often underdeveloped and are at greater risk of experiencing respiratory and cardiovascular problems.

“It is a challenge to study pre-term situations because the normal labour process in humans is still not fully understood,” says Slater. She and her team, including a clinical collaborator who is an obstetrician, and a medical student−are however, forging ahead.

Slater and her team are using muscle cells from the uterus that are extracted during ceserean deliveries and are studying how these cells and their associated pathways operate. Additionally, they are applying interventions (drugs and gene regulation) to reverse the behaviour of the uterus−that is, to prevent uterine contraction and therefore stop the evolution of premature labour.

Slater is particularly interested in the prostaglandin E2 (PGE2) pathway. Since PGE2 is often used to induce labour, preventing its synthesis within the uterus is a common treatment for preterm labour. Unfortunately, this is not as simple as it sounds, as PGE2 can cause contraction or relaxation in different circumstances.

There are also four possible receptors for PGE2 and for it to work effectively to help those at risk of premature labour it will be critical to zero-in on the right one.

“Since labour is also triggered by factors like inflammation, preterm labour is likely the result of a cascade of events in which inflammation develops early,” says Slater. “Applying anti-inflammatory interventions could be another way to stop or mitigate contractions.”

Slater says preterm labour is a complex issue and not a result of any single factor. “The solutions will likely be as varied as the causes.”

Cohort studies mother-baby pairs in Alberta It’s one of the largest pregnancy and birth cohort studies in Canada and the data collected from it will help researchers understand birth outcomes and women’s experiences during pregnancy.

The All Our Babies Cohort is made up of 3,300 mother-baby pairs in Alberta who were recruited for two main research objectives: to understand a woman’s experience during pregnancy and to predict preterm birth.

With the first baby born in 2008 and the final born in the summer of 2011, participants completed comprehensive questionnaires during pregnancy and follow-up questionnaires at four, 12, 24 and 36 months following birth. In addition to these data, biological samples such as blood and plasma were collected from approximately half of the cohort.

“Essentially what we’re interested in is the influence of early life experiences on what happens later in child development and maternal and family health,” says lead investigator Suzanne Tough, PhD, who is a member of the Faculty of Medicine’s Alberta Children’s Hospital Research Institute for Child and Maternal Health (ACHRI).

The study explores a variety of research areas such as health service access and use, maternal lifestyle, mental and physical health, social support, and birth and child development outcomes. While some components of the questionnaires remain consistent through each follow-up period, new areas of interest are also identified at each point. For example, at the 12 month follow-up, many women will be at the end of maternity leave so researchers are interested in their transition back to work.

Another focus of the cohort is to identify possible genetic markers for preterm birth. Biological samples are analyzed for these markers and incorporated into the other data collected. By looking at all these data collectively, Tough believes researchers may be able to understand the relative importance of specific genetic markers compared to environmental influences on birth outcomes.

“We want to develop effective interventions, and by collecting these data we can better understand where to target our strategy,” she says.

Donna Slater, PhD, is supported by Alberta Innovates – Health Solutions.

While the cohort study will provide plenty of information for her team’s purposes, Tough says that due to the size of the cohort they are also likely to see a number of babies who will develop specific conditions, such as asthma, that may be of interest to other researchers.

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Donna Slater, PhD

“Our hope is that researchers interested in some of these sub populations will use this cohort to build their own research.”

Suzanne Tough, PhD, is supported by Alberta Innovates – Health Solutions.

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McCaig Institute for Bone and Joint Health Nigel Shrive, PhD, director

Institute Overview

While primarily housed in the University of Calgary’s Faculty of Medicine, the McCaig Institute is comprised of researchers from five faculties who have come together to take multi or transdisciplinary approaches to achieve the institute’s goals. The consortium of investigators includes basic scientists, orthopedic surgeons, rheumatologists, kinesiologists and biomedical engineers, who bring diverse technologies and perspectives to bear on these complex chronic conditions. The primary focus of the McCaig Institute is basic and clinical research, with the goal of understanding the basis for bone loss and joint health and the development of these debilitating chronic diseases and conditions, which affect 15 per cent of Albertans.

The McCaig Institute interacts with the Alberta Bone and Joint Health Institute in relation to health services research, improving provincial interconnectivity. The McCaig Institute is also a focal point for interactions with other independent entities such as the Calgary Bone and Joint Health Program of Alberta Health Services. The objective of these interactions is to apply the institute’s successful research outcomes to patient populations effectively.

“The three independent components (McCaig Institute for Bone and Joint Health, the Calgary Bone and Joint Health Program, and the Alberta Bone and Joint Health Institute) and their associated partners come together to form a unique Knowledge Translation Network. This enhances the return on research investment to the benefit of patients and those at risk of becoming patients,” says Nigel Shrive, PhD, director of the McCaig Institute for Bone and Joint Health.

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Over the past year there have been many successes for the McCaig Institute. Last September, the second annual Music in Motion fundraiser was held at the Jack Singer Concert Hall. Thanks to the generous support of the philanthropic community, over $1-million was raised for bone and joint health in Alberta and the McCaig Institute was one of the benefactors of these funds.

The McCaig Institute also celebrated the achievements of many of our members, most notably, Dr. Marvin Fritzler who was one of six recipients of the 2011 CIHR-CMAJ Awards for Top Achievements in Health Research. Through his research, Fritzler has identified novel autoantigens that resulted in new diagnostic testing and biomarkers for auto immune diseases.

MSc student Ken Fyie

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The McCaig Institute for Bone and Joint Health maintains the commitment of Mr. J.R. “Bud” McCaig to discovering the underlying basis of chronic joint conditions such as osteoarthritis, rheumatoid arthritis and other related diseases. With the knowledge gained, the institute strives to find treatments for these diseases to improve the quality of life for Albertans, and to prevent the development of these conditions in future generations.

Study investigates bone and joint replacement wait times For the past few years Ken Fyie has been collecting data surrounding primary-to-specialist referral processing for elective hip and knee joint replacement surgery. An economist by trade and an MSc student in Community Health Sciences, Fyie is conducting his research in association with the McCaig Institute for Bone and Joint Health and the Alberta Bone and Joint Health Institute, and is hopeful the results will ultimately aid in leading to strategies to reduce referral wait times.

With Alberta Health Services looking to implement an electronic referral system for hip and knee musculoskeletal (MSK) clinics, Fyie’s original plan was to pursue a before and after comparison once the system was implemented. However, when he began his introductory research, he discovered that how and where processing delays increased referral wait times had never really been looked at academically before. As such, he’s hopeful his research may actually help to inform the design of that system.

Through a series of interviews with clinicians, patient chart reviews, and time-tracking observations of clinic staff, Fyie was able to amass a collection of extensive and sometimes unexpected information. “About 11 to 15 per cent of referral wait time wasn’t a result of patient-driven causes or challenges scheduling a surgeon, but because it was taking that long in the health-care system for a referral to be sent to and accepted by the specialist,” he says.

According to Fyie’s data, the primary contributor to this kind of early-stage delay is inconsistency. Different clinics require different information from general practitioners to consider the referral complete and as a result 20 to 54 per cent of the referrals were rejected on first receipt, primarily due to missing information. Additional variations in the referral processing systems between clinics compound the problem. The study showed that when using consistent definitions between clinics, wait times, from when a referral was made to a surgical consultation, averaged 51-217 days.

Fyie proposes a number of simple actions to address these issues, such as introducing consistent processing rules and systems for all clinics, creating a standardized referral form, and implementing a central intake administration, which, in conjunction with a provincewide “next available surgeon” option for patients, could eliminate competing streams of referral requests and improve wait times for patients. “By making things a little bit more efficient, we can get patients through quicker or at least get them some treatment in the meantime,” says Fyie.

Fyie hopes his research might not only inform the design of the electronic referral system, but that it will also provide the starting point for a database to track wait times in response to various policy interventions. “We should be tracking these measures long term. To be able to give patients this information would be fantastic.”

Team receives osteoarthritis team grant Osteoarthritis (OA), the degeneration of joint cartilage and bone, is a disease for which there is currently no cure. The University of Calgary’s Dr. Marvin Fritzler, Tannin Schmidt, PhD, and Roman Krawetz, PhD, all members of the McCaig Institute for Bone and Joint Health, are joining forces under an Alberta Innovates − Health Solutions (AIHS) OA Team Grant with the common goal of finding novel diagnostics that could lead to early and more effective interventions for the disease.

Lubricating properties Tannin Schmidt, PhD, is researching the lubrication of cartilage in the joints, and in particular, how these properties in the knee can be altered following injury.

While OA can be caused by a number of factors, more than half of those individuals who experience a severe joint injury will develop the disease within 15 years.

Schmidt is looking at lubricin, one of the lubricating proteins found in synovial fluid−a fluid found in joint cavities. He says some OA patients have been found to have low levels of lubricin in their joints, leading him to believe that by injecting lubricin back into the affected joint, it could potentially either prevent initiation or slow the progression of OA. Stem cell possibilities Stem cells are thought to be responsible for the “wearand-tear repair” of everyday life. They are found in most tissues of the body, with the exception of cartilage, according to Roman Krawetz, PhD. Krawetz has, however, been able to isolate stem cells from the synovial fluid and tissue which surrounds the cartilage, leading him to hypothesize that the synovial stem cells are responsible for cartilage repair. His group has found that within a joint affected by OA, the synovial stem cells are dysfunctional, which may lead to cartilage degeneration. Krawetz is researching how these stem cells become dysfunctional, in hopes of understanding how to regain normal functionality.

Early diagnostics Dr. Marvin Fritzler is searching for biomarkers which could be indicators for early OA. Using human blood samples, Fritzler is intent on discovering early diagnostic markers which could lead to personalized therapy for OA sufferers.

His research aims to predict subsets of OA that are at risk of developing severe disease. These studies will also attempt to identify individuals who will respond to a given OA therapeutic and also those that are at risk of serious side effects from OA therapeutics.

In discovering novel diagnostics and early interventions for OA suffers, Fritzler, Schmidt and Krawetz hope their research could aid in the understanding of how to slow the progression of the disease, ultimately leading to improved quality of life for those who suffer from it.

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Southern Alberta Cancer Research Institute Steve Robbins, PhD, director

Institute Overview The fight against cancer is one that is being fought on multiple fronts and continues to achieve many victories.

The Southern Alberta Cancer Research Institute (SACRI), a partnership between the University of Calgary’s Faculty of Medicine and Alberta Health Services-Cancer Care, has identified three scientific divisions to facilitate their strategic approach to research: Division of Preventive Oncology  Our established program in the field of molecular cancer epidemiology provides us with an excellent foundation on which to grow in the area of cancer prevention and control.

Division of Experimental and Cellular Therapeutics  Encompasses our established programs in genomic instability and cellular aging, new targets/treatments for brain tumours and new targets and novel treatments of pediatric cancers.

Division of Applied Oncologic Sciences  Includes a number of essential research platforms including novel biomarker discovery, diagnostic imaging and medical biophysics, as well as the essential programs directly linking patient quality of life (distress screening, survivorship, pain management and palliative care).

As cancer represents hundreds of different diseases, we must move past a one-size-fits-all strategy and treat each type of cancer based on its own unique genetic alterations. In Calgary we have used some state-ofthe-art technology to make this precision-based cancer medicine a reality.

Calgary is recognized world-wide as being a centre of excellence in patient care, clinical trial activity and medical research advances. Activities at the University of Calgary, the Tom Baker Cancer Centre and the Alberta Children’s Hospital ensure that not only do cancer patients in southern Alberta continue to receive the best cancer treatments, but also that these treatments continue to improve, based on the innovative science and knowledge of the physicians and scientists working in the field.

We continue to maintain one of the highest accrual rates to cancer clinical trials in the world. Progressive and provincial integration of cancer clinical trials is designed to further increase these accrual roles, while continuing to provide a high level of cancer care to all Albertans.

Although the landscape of health care is changing in Alberta, SACRI continues to work closely with Alberta Health Services and the University of Calgary.

Building on community partnerships remains a key initiative at SACRI, something that is achieved through our Community Partners Advisory Council, which includes several members of the community as well as representatives of supporting foundations.

Janine Giese-Davis, PhD

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Our researchers and health professionals are committed to understanding and identifying risk factors for cancer and other diseases and health conditions.

Our commitment to this cause is highlighted by our involvement with the Tomorrow Project−a longitudinal study created to understand what causes disease such as cancer, heart disease and other long-term health conditions. In Alberta alone, approximately 50,000 people will be taking part in the project.

2AA07 3280 Hospital Drive NW, Calgary, AB, T2N 4Z6 www.sacri.ucalgary.ca PAGE 16

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In Alberta alone, there are approximately 100,000 cancer survivors.

Research helps cancer survivors The emotional effects of cancer don’t always stop when treatments do, and Janine Giese-Davis, PhD, and the CancerBRIDGES Survivorship Team are researching ways to make the post-treatment process for cancer survivors less challenging.

“Post active-treatment is a time period when patients often feel very lost and abandoned,” says Giese-Davis, a member of the Faculty of Medicine’s Southern Alberta Cancer Research Institute (SACRI). “All of a sudden they are back in their communities and life is nothing like it was before they were diagnosed with cancer.”

Giese-Davis’ team is researching the effects care plans have on the well-being of cancer survivors. The research is one of only four care plan studies in Canada to receive funding from the Canadian Partnership Against Cancer (CPAC). As such, Giese-Davis says her team is ahead of the curve when it comes to conducting research into survivorship−a term encompassing those who are living with and beyond cancer.

In the study, 60 cancer survivors received care plans, which were delivered by a nurse immediately following treatment.

Each care plan included a personalized summary of what the survivor was initially diagnosed with, what treatments they received, and their follow-up plan. Additionally, information was included in regards to coping and adjustment, symptoms to watch for as signs of a possible recurrence, as well as a breakdown of symptoms they may have already experienced as a result of treatment. These care plans were handed to the patients, scanned into the oncology record, and faxed to family physicians to facilitate communication.

“This information really normalizes their experience and what they’re feeling,” she says.

The care plans also provided an opportunity for survivors to talk to a health-care professional about their goals and priorities in other areas of their lives, such as finances, spirituality and relationships, that may also have suffered following their diagnosis.

Participants were followed for six months after receiving the plans and completed questionnaires in regards to their experience−some were also interviewed. The results have shown the majority of patients felt the care plans were a positive experience for them. Health-care professionals have also provided useful feedback for the purpose of creating a more comprehensive delivery of the care plans.

Giese-Davis says survivorship needs attention and she feels lucky to have received funding to conduct some of the first research in Canada on the topic.

“We have programs to help cancer patients with their emotional needs at the time of diagnosis but survivorship has often been neglected until now.”

For more information, go to www.cancerbridges.ca

Mending your DNA Cancer is a disease of genomic instability−a loss of DNA sequence fidelity that occurs when our DNA is unable to properly repair itself from damages such as strand breakage. While some damage to our DNA occurs naturally, such as with age and when our cells grow and divide, it can also occur as a result of environmental influences such as radiation exposure. Aaron Goodarzi, PhD, a member of the Faculty of Medicine’s Southern Alberta Cancer Research Institute (SACRI), is studying how our cells repair DNA damage, which is key to understanding cancer biology.

The genetic information contained within each of our cells is made up of two intertwined strands of DNA. Breakages in these strands of DNA occur frequently, and Goodarzi is primarily interested in the most dangerous type−the DNA double-strand break. While all living cells have built-in DNA repair mechanisms to mend strand breakages, occasionally these breaks are irreparable and the cells die off, or they are repaired erroneously resulting in genetic mutations. If those mutations then inactivate anti-cancer genes or turn on pro-cancer genes, tumours can form.

According to Goodarzi, cellular aging is a primary contributing factor to how well we deal with DNA breakages. “As we age, our ability to faithfully repair DNA double-strand breaks decreases and, as a result, we may eventually get cancer,” he says. “Understanding how we develop that cancer with age can tell us a lot about the fundamental mechanisms of our genome, with the aim to not necessarily defeat aging but to age well, meaning we live long and happy lives without developing these diseases.”

Additionally, environmental radiation exposure, both ionizing (associated with an x-ray, for example) and ultraviolet (from sunlight), can result in the premature aging of cells, compounding the effects of natural aging in our cells. In this case, our intrinsic DNA repair mechanisms may become too overwhelmed to make all of the necessary repairs. This can lead to an accumulation of DNA damage in cells, fuelling genome instability that may accelerate aging or, at worst, cancer formation.

“You’ll notice that people who chase the sun their entire lives will look much older a few years down the line,” he says. “Their cells have had to repair the damage and replicate themselves so much that they can’t do it anymore.”

However, when it comes to treating cancer, Goodarzi says when the DNA damaging quality of radiation is harnessed, such as in the field of radio-oncology, it can be utilized as a powerful tool to kill a tumour.

“Right now there are still some nasty side-effects from radiation therapy,” he says. “If we can understand the effects of radiation and how our cells repair themselves, we can perhaps improve the efficiency of radiation therapy in terms of patient outcomes, whether it’s tumour reduction or preventing some of the toxic side-effects.”

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Institute for Public Health Dr. William Ghali, scientific director

Institute Overview From clean air and drinking water, to immunizations or access to childcare and education, the health of our communities is directly influenced by the social, environmental, and economic conditions in which we live.

As the seventh and newest University of Calgary research institute within the Faculty of Medicine, the Institute for Public Health is dedicated to exploring the relationships between these health determinants: to remove inequities and improve health care delivery for our communities, and to produce optimal tools for public health research.

Institute for Public Health membership encompasses over 270 of Alberta’s top researchers and health professionals, drawn from multiple university faculties and schools, health service providers, government agencies, and community organizations. Through these unique partnerships, our initiatives are encompassed within and among nine thematic research groups:  Aboriginal Public Health  Environmental Health  Global Health

This infrastructure fosters a collaborative multidisciplinary approach to research that allows us to bridge the gap between scientific and public, bringing the latest and best knowledge to the right people at the right time.

A healthy, thriving population is essential for the continued development and success of any society.

Through evidence-informed interventions we aim to create positive new trends in health to impact Canadians and others around the world in a visible and meaningful way, both now and in the future.

Breakdown of Institute for Public Health membership:  50 per cent from the Faculty of Medicine  Five per cent from other University of Calgary faculties (nursing, kinesiology, veterinary medicine, social work, arts)  35 per cent from Alberta Health Services (AHS)  Remainder from other municipal and provincial agencies and institutions

 Health Economics  Health Systems Performance Improvement  Population Mental Health  Population Health and Inequities  Primary Care  Research Methods for Public Health

 Lindsay McLaren, PhD

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Interventions key to reducing dietary sodium Dietary sodium reduction strategies at the public health level are gaining ground around the world according to Lindsay McLaren, PhD, a member of the University of Calgary’s Institute for Public Health (IPH). But the future of Canada’s national strategy remains uncertain despite the fact that Canadians consume more than twice the recommended healthy dosage of sodium daily.

Using a compare and contrast method of investigation, McLaren is studying the implementation and impact stories of nations that have already made a population-wide strike against sodium consumption. Her research aim is to evaluate which interventions are equitable in their impact across socioeconomic lines, and consequently, how best Canada can follow suit.

Typically these interventions take three forms: education, nutrition labeling and food product reformulation. McLaren is anticipating her research will show that the first two forms are inequitable, as they both require people to purposefully act on information, and sometimes in the presence of economic barriers such as limited income. In contrast, food product reformulation, if done correctly, could have a major impact on our health−one that is evenly felt and could literally change the nature of the food supply, she says.

“In many cases, including what’s proposed in Canada, food product reformulation occurs or would occur on a voluntary basis, which means at the will of individual food companies.

Financially speaking, sodium is a food company’s dream.

It serves a wide range of functions: it can improve taste, texture, shelf life, etc., at very little cost,” says McLaren, suggesting many companies may not be quick to give it up.

She believes the idea of targeting food at the source through a mandatory or regulatory approach is crucial, especially considering that most of the sodium consumed in Canada comes from processed foods. “This isn’t a problem of people adding too much salt at the table or when they’re cooking, but sodium added to our food when it’s produced,” says McLaren.

While there has already been a great deal of effort to develop a national sodium reduction strategy, Canada continues to lag behind other nations in this regard.

McLaren hopes her research will provide some insight into not only the social and economic benefits of “leveling” the sodium consumption playing field, but into the usefulness of population-level health interventions in general.

“The health consequences of excess sodium intake, such as high blood pressure, stroke and cardiovascular disease, are costly to our health-care system. If we could even out the population so that everybody is at the same level as the rich, that’s a lot of avoidable cases,” says McLaren. “Like a number of public health interventions, this is relatively easy and low cost. So, why don’t we do this?”

Severe food insecurity is toxic to child health According to Statistics Canada, an estimated 5.5 million people in Canada are at risk of going hungry and 40 per cent of those affected are children. Recent research from the University of Calgary’s Institute for Public Health (IPH) shows that going hungry in childhood can be a major contributor to ill health in the future.

For almost 20 years, Dr. Lynn McIntyre has followed children enrolled in the Canadian National Longitudinal Survey of Children and Youth (NLSCY), to better understand the effects of hunger on children over time.

Children ranged in age from 0-11 years at the onset of the study in 1994, and data collected every two years since has included child hunger as well as a wide range of health outcomes and household socio-demographic characteristics, such as income and family structure, and education.

“Our study had an incredibly rich data set of almost 6,000 children allowing us to see that even one report of hunger had an impact on a child’s overall health,” says McIntyre.

Multiple episodes of hunger were even more likely to have an adverse affect on a child’s health over time. Chronic conditions in general, and asthma in particular, were observed among those who had experienced multiple episodes of hunger compared with those who were never hungry. These rates were also higher in girls than in boys.

Surprisingly perhaps, lack of nutrition was not touted as the main cause of these long-term adverse health effects. Instead, it appeared that the experience of a family being in extreme distress had the greatest negative impact on children.

Teaming up now with colleague Dr. Scott Patten, also a member of IPH and an expert in depression, McIntyre’s newest study using these data will examine whether or not childhood experiences of hunger are related to depression and other adverse mental health outcomes.

Hopefully, this research will provide evidence to theories that early childhood disadvantage changes brain chemistry resulting in problems later in life.

In the future, McIntyre and her team hope to advance public awareness and influence policy makers to address the issue of hunger and food insecurity at a national level.

“Child hunger is a medical emergency. As a society we need to find solutions for this, and not just for the children, but for the family unit as a whole.”

Lindsay McLaren, PhD is supported by Alberta Innovates – Health Solutions.

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Centre for Advanced Technologies John Reynolds, PhD, director

Overview The Centre for Advanced Technologies (CAT) is the technological cornerstone of biomedical research in the Faculty of Medicine. At CAT, researchers not only investigate and develop new biomedical technologies, they also provide advanced technological support to scientists investigating the basic building blocks of the human body–the science of genomes, proteins and metabolites.

“It is for good reason that the resources comprising the Centre for Advanced Technologies are referred to as ‘core facilities’–they are truly core to the research mission of the faculty. These technologies facilitate the broadest possible impact and are a key investment in the innovative program of research inquiry,” says Peter Macklon, director of CAT.

CAT brings together a wide array of technological facilities whose primary focus is to serve the research programs of the Faculty of Medicine. These facilities currently include:  Clara Christie Centre for Mouse Genomics: Transgenics Core Facility  Clara Christie Centre for Mouse Genomics: Embryonic Stem Cell and Targeted Mutagenesis Core Facility  Computed Microtomography  Health Sciences Animal Resources Centre (HSARC)  University Core DNA Services (UCDNA Services)  Southern Alberta Mass Spectrometry Facility  Flow Cytometry Facility  Microscopy and Imaging Facility  Biomedical Technical Support Centre (BTSC)  Central Sanitation and Sterilization (CSS) Additionally, in partnership with the Faculty of Veterinary Medicine, a jointly managed core-facility provides histology/histopathological services to researchers.

 Richard Pon, PhD

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New facility opens door for new research A new genomics and bioinformatics facility in Calgary enables researchers access to next-generation DNA sequencing technologies which have been revolutionizing the fields of genomics and personalized medicine.

This is exciting news, as new sequencing technologies have made it practical to fully sequence the entire genome of any individual and in theory, be able to understand the genetic determinants of every aspect of that person’s life.

“The facility is important for Calgarians because it is the first one in Alberta with a focus on human health.

Facilities in Lethbridge and in Edmonton are primarily concerned with plant and bovine genetics,” says Richard Pon, PhD, director of the new facility.

The facility is a partnership that includes the Centre for Advanced Technologies (CAT), the Faculty of Medicine’s Alberta Children’s Hospital Research Institute (ACHRI) and others; however, its services extend to all University of Calgary researchers. As it is developed, its services may be extended to researchers from other academic sites and industries.

The facility supports basic research in the life sciences, basic medical research, and clinical research. Through a partnership with Alberta Health Services, clinically relevant research results and new diagnostic genetic tests will eventually be turned into improved patient services.

Since January 2011, sequencing projects of different types have been evaluated, benchmarked, and a data analysis pipeline created. The genomic sequencing services opened to the entire university community on March 9 of this year.

“Every field in the life sciences can benefit from this genomic technology and leading edge research at the University of Calgary cannot be performed without it.

“Genomics is also important to several key areas of Alberta’s economy and significant opportunities are expected to arise as the role of genomics increases in the areas of personalized medicine, animal health, agriculture, the environment and bioinformatics,” says Pon.

According to the 2011 World Malaria Report, globally, malaria mortality rates have fallen by more than 25 per cent since 2000.

Malaria-causing parasite investigated Malaria is a tropical disease caused by a parasitic infection transmitted to people from the bite of a mosquito. Current parasitic-killing therapies used to treat malaria can take over 48 hours, after administration, to become effective. In severe cases of the disease, death can occur before the drugs have a chance to work.

The Faculty of Medicine’s Dr. May Ho is taking a unique approach to understanding malaria. Rather than trying to discover new ways to kill the parasite, she is interested in how the parasite survives in its host environment. By understanding this process, Ho believes new therapies could be developed to limit the parasite’s ability to survive in those it infects, which could potentially lead to rapid therapeutic interventions for patients who present with severe malaria.

Once in the bloodstream the malaria-causing parasite invades individual red blood cells (RBC) in which it grows and multiplies until the cells burst. This process releases a multitude of parasites that then invade other RBC. What is particularly unique about the parasite is that it manipulates the RBC to attach to endothelial cells, which line the inside of blood vessels. From here, the parasite is well positioned to complete its life cycle and avoid being “filtered” out by the spleen. “This is one of the parasite’s survival mechanisms,” says Ho. Ho, along with her student Shevaun Davis, used the atomic force microscope (AFM), housed by the Centre for Advanced Technologies (CAT), to measure the adhesive force between the parasite-infected RBC and human endothelial cells. The microscope uses a fine flexible probe which allows for the measurement of detachment forces down to the picoNewton level (approximately one trillionth of a newton–the standard measurement of force). With the assistance of this equipment, they discovered that once the parasite binds to the cells the adhesion force increases with time, through modifications of the host cells. This phenomenon, which was published in The FASEB Journal in November 2011, can be attributed to a number of molecules, including the protein CD36.

“Without the Centre for Advanced Technology this kind of study would not have been done,” Ho says.

Ho acknowledges that many molecules are likely contributors to the adhesion process and says she will continue to search for more.

Dr. May Ho is supported by Alberta Innovates – Health Solutions.

Ho and Davis acknowledge the Snyder Institute’s Live Cell Imaging Core for the use of their confocal microscope, which contributed to their findings.

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Calgary Centre for Clinical Research Dr. Michael D. Hill, director

Overview The Calgary Centre for Clinical Research (CCCR) is a clinical trial and epidemiology coordination facility, and the first completely integrated clinical trial centre in Calgary. Designed to lead and conduct large clinical trials by Calgary investigators and their colleagues from around the world, the CCCR also provides support to health investigators within Alberta Health Services, the Faculty of Medicine’s research institutes, and other faculties at University of Calgary.

The centre is founded upon the Faculty of Medicine’s philosophy of flowing research discoveries from the laboratory bench to the bedside of patients and beyond. It is set up to enable clinicians and scientists to collaborate more efficiently on clinical research by working directly with patients, rapidly applying their findings in the laboratory, and developing new medical solutions for patients.

We have focused on growing and consolidating clinical research administrative activities. The Heritage Medical Research Centre (HMRC), located in the Teaching, Research and Wellness building, features space for clinical assessment of patients, patient beds and treatment chairs for intravenous infusions of study

medications; an in-house research pharmacy (a sub-site of the Foothills Medical Centre pharmacy); and laboratory facilities for preparing specimens for shipping. The space is being used for both industry-sponsored research as well as publically funded projects, and has shown increasing activity after the move last year.

There is a general move to provincialize clinical research systems for both ethics and regulatory affairs. With legal services provided by a single source for both Alberta Health Services and the University of Calgary, contractual delays have been decreased substantially.

Locally, we have moved a previously developed system onto the Faculty of Medicine’s internal intranet network, and rollout of this electronic platform for document submission and management was completed in May 2011.

The CCCR continues to be involved with the advancement and support of clinical research in southern Alberta, and ultimately assisting in the clinical care of Albertans.

The CCCR will further support Alberta Health Services’ infrastructure, programs and services going forward, and will continue to play a vital role in the ongoing success of those involved in clinical research.

According to the Canadian Institutes of Health Research (CIHR), population projections suggest that between 23 and 25 per cent of the Canadian population will be over the age of 65 in the year 2031.

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Longitudinal study aims to help individuals age well We’re all going to age, and the Faculty of Medicine’s Dr. David Hogan is involved in research he hopes will help us understand how to age well.

The Canadian Longitudinal Study on Aging (CLSA) will follow 50,000 Canadians between the ages of 45 and 85 years (at the time of recruitment), over the course of two decades. By identifying factors that contribute to healthy aging, the study will inform the future of our healthcare system. There are 10 data collection sites across the country and Calgary’s site, located in the Heritage Medical Research Clinic of the Calgary Centre for Clinical Research, is the only one in Alberta.

“The study is a bit like an RRSP for the country,” says Hogan, who is the lead site investigator for the Calgary location. “Hopefully this investment in the study now, will lead to benefits down the road in ensuring Canadians age well and that we’re efficient in using the resources we have.”

With recruitment in Alberta beginning in March of this year, randomly selected potential participants will be asked to take part. A preliminary interview will be conducted in their homes to collect information about their personal background, health history and lifestyle.

Participants will then be invited to a data collection site where they will undergo a more detailed physical and psychological examination. Biological samples such as blood will be collected for further analysis. Researchers will collect detailed information from each participant every three years for the duration of the study.

While similar longitudinal studies have been done worldwide, CLSA is specific to the Canadian population and will address our unique needs.

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“Many of our population are baby boomers just turning 65, and how they age will have a significant impact on our society,” says Hogan. “We are also very much a country of immigrants. We have people from all over the world and that could put a particular spin on how aging in Canada differs from other parts of the world.”

Dr. David Hogan

Hogan says factors such as our geography also make Canada unique when compared to other countries that have done similar studies, in that we have a relatively small population- to-land-mass ratio, with some areas, particularly the far north, only sparsely populated.

Hogan says the Calgary Centre for Clinical Research is essential to the success of the Calgary site, as it will serve as the data collection “hub” for participants in and around Calgary. It’s anticipated the centre will see approximately 3,000 CLSA participants.

“If the Calgary Centre for Clinical Research, and in particular the Heritage Medical Research Clinic, wasn’t here, we wouldn’t be doing the study in Calgary,” says Hogan.

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Graduate Science Education Frans van der Hoorn, PhD, associate dean

Overview

 Biochemistry and Molecular Biology  Biomedical Technology  Cardiovascular and Respiratory Sciences  Community Health Sciences  Gastrointestinal Sciences  Immunology  Microbiology and Infectious Diseases  Medical Science, with specializations in:  Cancer Biology  Critical Care Medicine  Joint Injury and Arthritis  Medical Education  Molecular and Medical Genetics  Mountain Medicine and High Altitude Physiology  Neuroscience The Office of Graduate Science Education supports and administers student recruitment, admission, applications for funding, student career support, course coordination and timetabling, and monitors the quality of all programs to ensure optimal student education and experience. In 2011, our graduate programs convocated 102 students: 19 MBT, two MDCS, 49 MSc and 32 PhD. Five of these students graduated with joint degrees: one MBT/MBA, two MD/MSc and two MD/PhD.

Graduate Science Education 3330 Hospital Drve NW, Calgary, AB, T2N 4N1 medicine.ucalgary.ca/grad PAGE 24

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“Graduate education depends critically on the personal mentoring of the student by a faculty member, which ensures a high quality education. Over 189 faculty members are involved in supervision with 249 serving on supervisory committees. The one-on-one instruction is supplemented by over 126 intensive graduate courses in the Faculty of Medicine,” says Frans van der Hoorn, PhD, associate dean of Graduate Student Education.

In addition, 54 graduate students are registered in the Leaders in Medicine combined program, where they earn a joint degree such as MD/MBA, MD/MSc or MD/PhD. The objective of this program, one of the largest of its kind in North America, is to train clinician-scientists for academic medical research careers, and for careers in the design, management and implementation of healthcare delivery programs.

Over 33 per cent of our graduate students received competitive awards, scholarships and/or prizes including those from federal agencies such as the Canadian Institutes of Health Research (CIHR) and the Natural Sciences and Engineering Research Council of Canada (NSERC); and provincial agencies including Alberta Innovates – Health Solutions (AIHS) and the Alberta Cancer Foundation. This has brought in close to $3.25 million in support of research.

PhD student Lisa Allen (centre) in Tanzania.

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Graduate students are an integral part of the research enterprise at the Faculty of Medicine. They are our future scientists who will play leadership roles in academia, business and society. In the researchintensive environment at the Faculty of Medicine, 603 graduate students were registered throughout the 2011 year–21 per cent of them international students–in the masters (MSc, MDCS, MBT) and doctoral (PhD) programs, carrying out innovative research with some of the best researchers in their fields. Through the Faculty of Medicine’s interdisciplinary graduate training environment, students are registered in one of the following graduate programs, which cut across academic departments and research institutes:

Prestigious scholarship supports valuable research Public health campaigns are implemented to address health issues at the population level; however, these well-meaning interventions are sometimes accompanied by harmful unintended consequences to those they aim to help. PhD student Lisa Allen made this observation during her travels to Tanzania as part of the Global Health program, and is currently researching the topic as part of her dissertation.

“There’s really no current operational definition for what unintended consequences are, no classification system, or way to predict or evaluate them in public health interventions,” she says, adding that while her research focuses on low to middle income countries, harmful unintended consequences happen in all parts of the world.

In Tanzania for instance, Allen observed that while there were campaigns for women and children to receive subsidized insecticide treated bed nets, the nets were only available in urban centres, while many of those in need lived in remote areas. In order to take advantage of the intervention, these women and children had to travel−often for hours−requiring resrouces they didn’t have.

To conduct her research, Allen has been reviewing academic literature based on previous public health intervention studies and is thematically analyzing how and where unintended consequences have occurred.

Because of the complexity of the interventions and the fact that unintended consequences often go unreported, determining causality is often challenging.

For this reason, Allen says it’s important to explore possible causes on all fronts: cultural, economic, psychosocial and environmental. Ultimately, she aims to not only operationally define unintended consequences as associated with public health interventions, but to develop a framework that can be utilized by practitioners and researchers who are trying to evaluate these campaigns. She hopes that by utilizing the framework, the benefits of such interventions could be maximized and the harmful unintended consequences, minimized.

“A harmful unintended consequence is something you didn’t know was going to happen−if it can be predicted, hopefully it can be prevented.”

While Allen’s research is in its infancy, its value has already been recognized, as it has earned her a Vanier Canada Graduate Scholarship−a prestigious and competitive scholarship designed to attract and retain world-class doctoral students.

“The Vanier Scholarship has been a really amazing thing,” she says. “I feel so humbled because you’re looked at as having such great potential. It’s great to know people are supporting me.”

Side-effects of popular drugs studied A common treatment for headaches, inflammation and any type of acute or chronic condition is non-steroidal anti-inflammatory drugs (NSAIDs). While these drugs, including popular brands such as Advil, Tylenol and Celebrex, may work for symptom relief, taking them, especially long-term, does come with side-effects.

MSc student Dr. Matiram Pun is researching the physiological mechanisms behind these side-effects and is particularly interested in how individuals suffering from obstructive sleep apnea (OSA)−a chronic condition that causes individuals to essentially stop breathing periodically while sleeping−are affected by long-term NSAIDs use.

Approximately three per cent of the Canadian population suffers from OSA, while 25 per cent have risk factors, such as obesity, for developing the disease. OSA is independently associated with an increased risk of heart attack, stroke and hypertension−consequently individuals with OSA requiring NSAIDs could be at increased risk of developing health conditions of the heart, brain and overall vascular system.

Over the past year, Pun has studied healthy adult volunteers by exposing them to induced intermittent hypoxia cycles−cycles of high and low levels of oxygen representative of the oxygen levels experienced by OSA sufferers. The participants took either NSAIDs or a placebo for five consecutive days, in a clinically relevant dosage regimen, and on the fifth day, went for lab testing.

At various intervals during exposure, biological samples and other measurements such as blood pressure, blood oxygen saturation and blood flow to the brain were taken to investigate the presence and behavior of specific molecular markers responsible for the regulation of blood pressure, brain blood flow, clotting mechanisms and kidney homeostasis.

“In causing the intermittent hypoxic stimulus, we are looking at how the drugs act differently under these hypoxic challenges in a healthy human being,” he says. “By going down to the molecular level and teasing out molecular pathways, we will be able to say with confidence what physiological aspects are affected and what causes specific side-effects.”

Since Pun is inducing the scenario in healthy individuals, he says his results are not only specific to OSA sufferers.

For instance, the intermittent hypoxic state participants are exposed to is also representative of exposure to a change in altitude, which is applicable to hikers and miners who frequent high altitude environments.

Pun is in the analysis phase of his research and hopes the information he collects will provide more insight into the physiological basis of the side-effects caused by NSAIDs use. “By understanding how the drugs work in a molecular basis, we could potentially understand how to prevent their side-effects.”

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Chairs and Professorships Endowed chairs and professorships are established by the philanthropic community and/or organizations to develop, promote, and recognize research excellence throughout the university. The income generated by the endowments enhances the recruitment and retention of internationally renowned candidates who will provide leadership and vision to specific research programs.

Endowments have virtually matched pace with the overall growth of the faculty. Estimated at $40-million 10 years ago, the total market value of the endowment now represents over $127-million, plus an additional $22-million dedicated to the Faculty of Medicine but held at external charitable foundation. Twelve years ago we had one endowed research chair, today we have 49 chairs and professorships

Alberta Cancer Foundation Chair in Brain Tumor Research Dr. Greg Cairncross

Brenda Strafford Foundation Chair in Alzheimer Research In search

Alberta Cancer Foundation The Weekend to End Women’s Cancer Chair in Breast Cancer Research Selection in progress

Brenda Strafford Foundation Chair Geriatric Medicine Dr. David Hogan

Alberta Children’s Hospital Foundation Barb Ibbotson Chair in Pediatric Hematology Faisal Khan, PhD Alberta Children’s Hospital Foundation Chair Pediatric Research Dr. Brent Scott Alberta Children’s Hospital Foundation Cuthbertson and Fischer Chair in Pediatric Mental Health Frank MacMaster, PhD Alberta Children’s Hospital Foundation Dr. Robert Haslam Chair in Pediatric Neurology Dr. Jong Rho Alberta Children’s Hospital Foundation Kinsmen Chair in Pediatric Neurosciences In search Alberta Children’s Hospital Foundation Professorship in Child Health and Wellness Brent Hagel, PhD Alberta Children’s Hospital Foundation Professorship in Pediatric Rehabilitation Carolyn Emery, PhD Alberta Children’s Hospital Foundation Professorship in Pediatric Surgery Dr. David Sigalet AMF/Hannah Professorship in the History of Medicine Dr. Frank Stahnisch Andrew Family Professorship in Cardiovascular Research Dr. William Cole Arthritis Society Chair in Rheumatic Disease/Rheumatology Dr. Marvin Fritzler Arthur J.E. Child Chair in Rheumatology Research In search Bob and Nola Rintoul Chair in Bone and Joint Research Steven Boyd, PhD

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FACULT Y OF MEDICINE Research Report 2011-2012

Husky Energy Alberta Children’s Hospital Foundation Chair in Child and Maternal Health Dr. Brent Scott Jessie Boden Lloyd Prof.

Dr. Chris Mody

Cal Wenzel Family Foundation Chair in Cardiometabolic Disease In search

John A. Buchanan Chair in General Internal Medicine Dr. William Ghali

Cal Wenzel Family Foundation Chair in Hepatology Dr. Mark Swain

Julia McFarlane Chair in Diabetes Research Dr. Pere Santamaria

Calvin, Phoebe and Joan Snyder Chair in Critical Care Research Paul Kubes, PhD

Kids Cancer Care Foundation Alberta Children’s Hospital Foundation Chair in Pediatric Oncology In search

Campbell McLaurin Chair Hearing Jos Eggermont, PhD Crohn’s and Collitis Foundation Chair in Inflammatory Bowel Disease Research Keith Sharkey, PhD Dr. Frank Leblanc Chair in Spinal Cord Injury Dr. Peter Stys Enbridge Research Chair in Psychosocial Oncology Linda Carlson, PhD Engineered Air Chair in Cancer Research Susan Lees-Miller, PhD

Lance Armstrong Chair in Molecular Cancer Epidemiology Hans Vogel, PhD McCaig Professorship in Joint Injury and Arthritis Dr. Cy Frank Merck Frosst Chair in Cardiovascular Research Dr. Todd Anderson N. B. Hershfield Professorship in Therapeutic Endoscopy In search Novartis Chair in Schizophrenia Research Jean Addington, PhD

GSK Professorship in Inflammatory Lung Disease Richard Leigh, PhD

Ohlson Family Professorship in Head and Neck Surgery Dr. Joseph Dort

Heart and Stroke Foundation Chair in Cardiovasc. Research Dr. Henry Duff

Parkinson’s Society of Southern Alberta/Suter Proffessorship in Parkinson’s Research Dr. Bin Hu

Heart and Stroke Foundation Chair in Stroke Research Dr. Andrew Demchuk

Roy and Vi Baay Chair in Kidney Research Dr. Brenda Hemmelgarn

Heart and Stroke Foundation-HBI Professorship in Stroke Research In search

Sutherland Professorship in GI/IBD Research In search

Heart and Stroke Foundation-Libin Professorship in Cardiovascular Research In search

Svare Professorship in Health Economics Herb Emery, PhD

Hopewell Professorship in Brain Imaging Richard Frayne, PhD

Tourmaline Oil Chair in Parkinson’s Disease In search

Hopewell Professorship in Clinical Neurosciences Research Dr. Sam Wiebe

Taylor Family Chair in Vascular Dementia In search

Financial Statement 2010-2011 Research Revenue (unaudited) | Sources of Revenue | Fiscal Year ending March 2011 Federal Government Tri-Council (CIHR, NSERC, SSHRC) 26,987,689.25 Canada Foundation for Innovation (CFI) 9,113,241.34 Other Federal Government 5,399,714.81 Canada Research Chair (Funded by CIHR) 4,325,000.00 Total Federal Government

45,825,645.40

Alberta Provincial Government AB Innovates-Health Solutions Provincial Research Envelopes Alberta Health Services (AHA) - includes Cancer Board Other Alberta Provincial Government Total Alberta Provincial Government

40,931,713.14

24,037,854.04 2,723,007.57 10,501,873.85 3,668,977.68

Other Canadian Universities and Hospitals Foreign Sources U.S.A. Sources (Public and Private) Other Foreign Sources Total Foreign Sources

4,682,058.17 10,213,579.17 583,629.24 10,797,208.41

Business

9,579,826.13

Non-Profit Organizations Provincial 3,002,885.53 National 3,470,334.25 Total Non-Profit Organizations

6,473,219.78

Foundations National Provincial Total Foundations

4,180,391.38 13,074,452.00 17,254,843.38

Endowments, Individuals and Internal Sources

15,395,802.36

TOTAL

150,940,316.77

A special thank you goes out to the foundations that supported the Faculty of Medicine for the fiscal year ending March 2011.

The Alberta Bone and Joint Health Institute The Alberta Cancer Foundation Alberta Children’s Hospital Foundation American Friends of the University of Calgary Inc The Brenda Strafford Foundation Ltd Calgary Drop-In and Rehab Centre Calgary Flames Foundation For Life Calgary Health Trust CanadaHelps.org Cenovus Employee Foundation Diabetes Association Foothills The Donald and Eleanor Seaman Family Foundation The Dutkevich Memorial Trust Fund Encana Cares Foundation Gastroparesis and Dysmotilities Association GPDA Haynes-Connell Foundation

The Hotchkiss Family Foundation The Hunter Family Foundation Lions of Alberta Foundation Multiple Sclerosis Society of Canada Parkinson Alberta Society The Peters Family Foundation RBC Foundation Riddell Family Charitable Foundation Ronald and Irene Ward Foundation Rose Foundation The Arnold P Gold Foundation The Calgary Foundation The Nat Christie Foundation The Palmer Family Foundation United Way of Calgary and Area

FACULT Y OF MEDICINE Research Report 2011-2012

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Office of the Senior Associate Dean (Research) 7th Floor, Teaching Research and Wellness Building 3280 Hospital Drive NW Calgary, Alberta T2N 4Z6