Innovation and Technology Improving Health - 2010-11 Research Report

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INNOVATION + TECHNOLOGY I M P R O V I N G

H E A L T H

2010 - 2011 Research Report

Editor Kyle Glennie

What are QR codes?

In this year’s report you will notice a QR code on many pages. Using your smartphone, you can scan these codes and your phone will immediately load a website that we’ve embedded in the code. Some codes lead to online videos we’ve made and others lead to websites that may interest you. Give it a try, many BlackBerries have QR code scanners already installed on the phone when you purchase it, and there are several QR code apps you can download for free on both your BlackBerry and iPhones.

Contributors Colleen Biondi Marta Cyperling Kyle Glennie Rochelle Murphy Krista Sylvester Karen Thomas Maria Turner Photography Carlos Amat Riley Brandt Dwayne Brunner John Gaucher Trudie Lee James May Bruce Perrault Concept and Design Kelly Budd, Radius Creative

Thank you to all institute and centre staff for their contributions

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2010 - 2011 Research Report

Message from the Senior Associate Dean (Research)

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Hotchkiss Brain Institute

The Calvin, Phoebe and Joan Snyder Institute of Infection, Immunity and Inflammation

Libin Cardiovascular Institute of Alberta

Alberta Children’s Hospital Research Institute for Child and Maternal Health

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McCaig Institute for Bone and Joint Health

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Southern Alberta Cancer Research Institute

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Calgary Institute for Population and Public Health

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Centre for Advanced Technologies

Calgary Centre for Clinical Research

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Graduate Science Education

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Chairs and Professorships/ Financial Statements 2009 – 2010

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Technology improving health When we set out to create this year’s Research Report for the Faculty of Medicine, I began speaking with my colleagues to get a sense of what we had accomplished in the past 12 months from a research standpoint. There has been several prominent research studies published in a variety of high impact—and indeed high profile—medical and scientific journals. We’ve made remarkable strides in the care we can now offer patients, including the first documented live cartilage shoulder transplant. And our work in the area of preventative medicine, indentifying biomarkers for medical conditions before they arise in a patient, is moving forward at an impressive pace.

You’ll find many of our success stories in the following pages, and I think after reading them you’ll come to a similar conclusion that I have; technology is not only ever-present in the vast majority of our work here, but it is also a catalyst for our breakthroughs and achievements.

Through the expertise of Dr. Matthias Amrein and his work with atomic force microscopy—which creates a three-dimensional image of a cell—researchers at the Faculty of Medicine were able to solve a 90-year old riddle relating to an immune booster present in almost all vaccines used today. Dr. Paul Kubes and his colleagues are viewing white blood cell activity in ways that few others in the world can. Through the use of spinning disk confocal intravital miscroscopy, Dr. Kubes has been able to create unprecedented real-time videos of white blood cell activity at the site of inflammation (see the video by scanning the QR code on page 8 with your smartphone).

Of course, utilizing technology is key for our ongoing research endeavours, but our research mission at the Faculty of Medicine goes beyond our laboratories; we aim to advance health and wellness on a broad scale in our communities and around the world. Through our health services and population and public health research we are accomplishing this, and our Faculty members in these fields are committed to a broad agenda of research, education, knowledge translation and community engagement.

To make all of this a reality we require strong partnerships and external collaboration with several groups outside of the Faculty of Medicine, something we are fortunate to have an abundance of. Our utmost appreciation goes to Alberta Health Services, the major funding agencies that support our faculty members, and the hundreds of organizations and individuals who give generously to our Faculty. Together they help propel our research forward, to the benefit of us all.

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

Dr. Richard Hawkes

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The Hotchkiss Brain Institute Dr. Samuel Weiss, Director

3330 Hospital Drive NW, Calgary, AB, T2N 4N1 www.hbi.ucalgary.ca | hbi@ucalgary.ca twitter @HotchkissBrain | facebook.com/hotchkissbrain

Institute overview

Reconnecting damaged nerves

The Hotchkiss Brain Institute (HBI) is a leading centre for neurological and mental health research, education and innovation. In the HBI, basic neuroscientists contribute to new clinical developments while they continue to make exciting fundamental discoveries. Clinical researchers and population health specialists help to define the medical problems that are pursued collectively through our priority areas of foundational and translational investigation.

His address may have changed, but his commitment to research sure hasn’t. Dr. Patrick Whelan, associate professor in the Department of Clinical Neurosciences at the Faculty of Medicine, may be on sabbatical at Emory University in Atlanta but he remains focused on finding solutions to nerve damage associated with conditions like spinal cord injury. From a distance he remains the designated leader of the Axon Biology and Regeneration theme at the Hotchkiss Brain Institute (HBI).

As such, he and his team investigate the basic science behind axonal disease and nerve regeneration.

The results of our efforts include hundreds of peer reviewed publications a year in leading international journals, over 20 investigator-initiated clinical trials running through the HBI Clinical Research Unit, and substantial funding successes. In 2009-2010, 50% off our membership held tri-council funding (funding from the Social Sciences and Humanities Research Council, the National Sciences and Engineering Research Council, and/or the Canadian Institutes of Health Research) including all of our basic scientists. HBI members secured $8.6 million from the Canadian Institutes of Health Research and a total of over $35 million in sponsored research. In addition to our researchers’ individual excellence, the HBI’s internal peer review process has helped our members collectively achieve success rates that are double or triple the provincial/national averages.

HBI core facilities—the Clinical Research Unit, Neuroimaging Research Unit and Molecular Biology Core—also support the success of our members. Our three priority foundational research themes and the four linked translational research programs provide hotspots for neuroscience interaction at the highest level for scientists and trainees, helping to make the HBI an outstanding place for neurological and mental health research.

Scan the QR code to learn more about the Hotchkiss Brain Institute and to see their website.

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Axons are small diameter fibers that can travel long distances connecting regions of the brain. If they are cut or impaired as a result of disease or trauma, communication from the brain to the spinal cord is compromised and serious problems with movement, sensory function and bladder control can occur. The Axon Biology and Regeneration group studies how to recover the health of axons.

“We’re interested in how we can promote recovery of function,” explains Whelan.

The anti-inflammatory drug minocycline demonstrates promise in this regard. After successful in-house testing with animals at UCalgary, spearheaded by Dr. V. Wee Yong, it has now advanced to multi-centre clinical human trials, coordinated by Dr. John Hurlbert and Dr. Steve Casha.

“It is teamwork at its best,” says Whelan, explaining the group’s success. “You need a strong basic foundation in science and excellent communication with clinicians to realize tangible results which are beneficial to people.”

Opening a new world of stroke treatments

Looking to the past can to improve our future

As co-leader of the Hotchkiss Brain Institute’s Cerebral Circulation Foundational Theme, Dr. Richard Frayne helps coordinate research about cerebrovascular diseases, such as stroke. He and other theme members focus on the science of such diseases and look for new mechanisms to cure them.

As leader of the Neural Systems and Behaviour theme at the Hotchkiss Brain Institute (HBI), Dr. Cam Teskey leads a collection of researchers who have a common interest in the brain, specifically how it changes at the neural and network level, as a result of experiences.

Lately they’ve partnered with the Calgary Stroke Program to look at better ways to manage and treat symptoms of stroke and vascular dementia. One area of joint study has been an integrated approach to “collateral circulation.” When small vessels in the brain are blocked, the brain can shuttle off the blood flow via other pathways, preserving brain function. But it doesn’t always do that. Researchers are examining when these “collaterals” open up and when they don’t and are devising a therapeutic intervention to open them up artificially.

One type of experience of particular interest to several members of the theme is stress. “All of us are under stress; sometimes it is acute and short-lasting and sometimes it is long-lasting,” explains Teskey. “As we learn more about the biology of stress systems we are better able to intervene and prevent long term damage to the brain.”

“If this (opening up collaterals) can be added to the treatment arsenal for a stroke neurologist, that would be a wonderful development,” says Frayne. “The longer the brain is without blood in a stroke, the less likely you are to fully recover.”

Another area of study associated with this collaboration is better interpretation of the small vessels anatomy in the brain. ”We understand the big pipes, and they are very important, but our evolution in understanding these other vessels is becoming increasingly important.”

Colleague Dr. Jaideep Bains, for example, has recently investigated how glial and neural cells in an area of the brain called the hypothalamus change under stress, and how a chemical compound known as endogenous cannabinoids mediate that change. A collection of team members are also using imaging technologies to determine how brain function changes with experiences. A behavioural neuroscientist, joining the team this summer, will add new energy and additional expertise to the collective.

Working with both human and animal models, researchers in this theme area are shedding light on the complex interface between brain function and experience, says Teskey. “That is a high priority for the HBI.”

By using function (collateral circulation) and structure (anatomy), researchers stand a much better chance at improving a patient’s outcome.

1.9 million

Number of brain cells that an average patient loses for every minute delay in treating a stroke. Researchers at the Hotchkiss Brain Institute are studying collateral circulation to help blood flow to the brain during a stroke to increase a patient’s chance at full recovery.

Source: The Heart and Stroke Foundation of Canada

Dr. Cam Teskey in the Health Research and Innovation Centre at the Faculty of Medicine.

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The Calvin, Phoebe and Joan Snyder Institute of Infection, Immunity and Inflammation Dr. Paul Kubes, Director Institute overview

With a vision of “scientific innovation today for a healthy tomorrow” the Calvin, Phoebe and Joan Snyder Institute of Infection, Immunity and Inflammation (Snyder Institute) has identified two strategic research themes—Host Microbe Interaction and Inflammation.

Within each theme we are able to bring together members with multi-disciplinary expertise and resources from a number of individual groups. These members are leading the fight against a host of serious health problems including, sepsis, MRSA, cystic fibrosis, type-1 diabetes, inflammatory bowel disease, chronic obstructive pulmonary disease, and asthma. It is our hope to enhance the quality of life of patients who suffer from pain and disability caused by these health problems.

We are continuously working to enhance our connections with industry and community. We have forged partnerships with our new Faculty of Veterinary Medicine colleagues, and a number of them are joining the Snyder Institute. This has led to significant increases in the amount of funding brought to the Institute, the number of newly employed high quality personnel, and in new expertise creating more research opportunities.

The Snyder Institute also features seven initiatives that enable both basic and clinical research:

3280 Hospital Drive NW, Calgary, AB, T2N 4Z6 www.iii.ucalgary.ca

modern radiographic and diagnostic technology, the facility allows researchers to perform human studies ranging from investigation into basic disease processes, to testing of new drugs.

5) Mouse Phenomics This facility promotes high quality, discovery based research by screening for new phenotypes of existing mouse strains in investigator driven models of interest, and by generating additional new phenotypic data using standard models. These results will contribute to the screening readout to enhance the Snyder Institute’s research effort.

6) Snyder Laboratory for Translational Research The original donation from Joan Snyder and an anonymous donor for critical care research—with matching funds from the Alberta government—has allowed the establishment of a laboratory that supports clinical research and clinical trials with fundamental molecular biology and cell biology data. A metabolomics component is also being implemented.

7) Education A new program in infection and immunology has been launched and over 10 studentships were announced to attract the best students to the Institute.

1) Cal Wenzel Chair in Hepatology A non-transplantation Chair in Hepatology established in the Snyder Institute is a first in Canada. Although liver diseases are stereotypically linked to alcohol or drugs, there are over 100 known forms of liver disease caused by a variety of factors, affecting everyone from infants to older adults. The chair will add to the liver unit through recruitment, research, education and infrastructure.

2) Microbial Communities Centre for Health and Disease The Microbial Communities Centre provides advanced equipment (flow cytometry, OV-100), expertise and diagnostic facilities for the study of polymicrobial infections and optimal treatment.

3) Live Cell Imaging Facility This well established core facility—funded by the Canada Research Chairs Program, the Canadian Foundation for Innovation and the Canadian Institutes of Health Research, provides training in imaging all aspects of the immune response from single cells invitro, to in-vivo imaging of the immune system and infections in brain, liver, skin, muscle and other organs.

4) Experimental Respiratory Suite The Experimental Respiratory Suite is a unique centre for translating basic pulmonary research into human research leading to new approaches for patient care. Equipped with

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Scan the QR code with your smartphone and watch Dr. Paul Kubes’ work showing white blood cells responding to an area of tissue damage in real-time.

Technology allows researchers to watch white blood cells in action

To say they are a fortunate bunch would be an understatement.

“Our laboratory is perhaps the only in Canada, and amongst a select few in the world, that have this technology so it is truly a privilege to contribute to this research.”

PhD candidate Braedon MacDonald isn’t exaggerating. As part of the Dr. Paul Kubes laboratory, MacDonald has the opportunity to use an imaging technology called spinning disk confocal intravital miscroscopy; a mouthful yes, but also an invaluable tool. Using it allowed the Kubes lab to discover that damaged tissue can release signals that attract white blood cells, and blocking these signals can prevent inappropriate inflammation.

“We have known how white blood cells find their way to sites of infection for many years, but understanding how, or even why white blood cells go to sites of sterile non-infectious tissue damage has been a real dilemma,” says Dr. Paul Kubes, senior author of the study and director of the Snyder Institute of Infection, Immunity and Inflammation.

“Recognizing that damaged cells release ‘bacteria-like’ signals that attract white blood cells and cause inflammation might allow for the development of a whole new class of therapeutics to combat inflammatory diseases.”

When the body is invaded by infection, the immune system counters by generating inflammation with deployment of white blood cells to the site of danger to kill invading bacteria. However, inappropriate inflammation occurs in the absence of infection when tissues are damaged, and this inappropriate response contributes to diseases such as heart attacks and stroke. Researchers used both experimental animal models and human white blood cells to discover that damaged tissue can release signals that attract white blood cells, and blocking these signal can prevent inappropriate inflammation. The findings were published in the prestigious journal Science.

Boosting our chances of creating new vaccines

They’re something most of us likely take for granted, yet they keep us safe from a myriad of diseases. Mumps, measles, hepatitis A, hepatitis B, the list goes on and on, and vaccines are our personal body guards. It may surprise you to know that 90% of the vaccines approved for use today contain an immune system booster called alum which vaccines need to be effective. And until now scientists had no idea how it worked.

“Understanding alum properties will help other vaccines because we are one step deeper into the mechanistic insight of adjuvants, or immune boosters, which are essential for human vaccines to work,” says Dr. Yan Shi, a member of the Snyder Institute of Infection, Immunity and Inflammation. The research, published in Nature Medicine, will help the medical community produce more effective vaccines and may open the door to create new vaccines for diseases such as HIV or tuberculosis.

“Knowledge provided in this study may help us manipulate alum with additional adjuvant components to direct an attack against major diseases which require a killer T cell response such as HIV, tuberculosis, and malaria,” says Tracy Flach, a graduate student from the Faculty of Medicine and the study’s first author.

The research reveals that alum interacts with a group of immune cells called dendritic cells via their cell membrane lipids. Dendritic cells, the sentinel of our immune system, heed the call of alum and move on to activate a group of T cells that control antibody production.

The breakthrough came as the team made use of a cutting edge technology developed in the Faculty of Medicine called single cell force spectroscopy. This technique allowed the researchers to study individual cells and measure their responses to alum.

Alum is a common grocery store staple used in pickling and has been in use for 90 years. It is very effective in inducing antibody responses and is the only human vaccine adjuvant approved for large-scale immunization.

Using the imaging technology, Kubes and his colleagues were actually able to create unprecedented real-time videos of the white blood cell activity at sites of inflammation. ”These powerful imaging systems allow us to tackle complicated problems by directly observing the activity of the immune system in the body,” says McDonald.

$3.5 million Donation made to the Snyder Institute by the Cal Wenzel Family Foundation to create the first ever research chair in Canada solely dedicated to hepatology, the study of the liver and its diseases.

Dr. Yan Shi and Tracy Flach in their Faculty of Medicine laboratory.

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Libin Cardiovascular Institute of Alberta Dr. Todd Anderson, Director 849, 1403 29 Street NW, Calgary, Alberta, T2N 2T9 libin.ucalgary.ca | todd.anderson@albertahealthservices.ca

Institute overview 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 world-class 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.

The Libin Institute is not a building. It is a ‘virtual institute’ in that it coordinates and integrates cardiovascular care delivery, training and research across southern Alberta.

• Providing world class treatment, using moder 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.

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.

1574

Number of firefighters who took part in a 10-year research study led by Dr. Todd Anderson, director of the Libin Institute. Each firefighter’s blood vessel function was measured every six months, the results of which led to the discovery that dysfunction of our blood vessel lining can predict who is at risk for developing coronary heart disease.

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Scan the QR code with your smartphone to learn more about the Libin Cardiovascular Institute of Alberta and see their website.

Predicting heart attacks before they happen Up to half of all deaths of individuals with heart disease occur suddenly. Add the fact that heart disease accounts for 30% of all deaths in Canada, and it becomes clear that being able to predict heart disease in patients before it develops would be incredibly helpful. Well that’s just what Dr. Todd Anderson, director of the Libin Cardiovascular Institute of Alberta, has done with his long term research into the underlying causes of heart disease.

Published research led by Anderson and his colleagues at four sites across Canada finds that endothelial dysfunction (blood vessel lining) can predict who is at risk for developing coronary heart disease. By identifying this new marker in patients doctors may be able to intervene early to prevent the progression of heart disease.

“The study has demonstrated that in addition to traditional cardiovascular risk factors, measures of blood vessel function are predictive of who goes on to develop cardiovascular complications,” says Anderson who is the study’s principal investigator.

The observational study followed 1574 healthy firefighters over a period of 10 years. At the beginning of the study each firefighter had an ultrasound of his brachial artery in the arm to measure blood vessel function and was then followed every six months for the 10 year period. Over the course of the study some of the study participants had cardiovascular events such as heart attacks and this allowed the research team to see what measurements correlated.

“The information obtained by these simple tests improves our ability to detect, among healthy individuals, those who will go on to have vascular events, with more precision and reliability than if we just tallied their traditional risk factors, as most clinicians do now,” says Dr. Francois Charbonneau, a co-investigator also from the Faculty of Medicine and a member of the Libin Institute.

“More research is required to see if these tests can be used in the population at large.”

Improving Canadians’ heart health is only the beginning “Chronic diseases like diabetes, kidney disease, high blood pressure and vascular disease are the quiet epidemic of our time.”

That statement made by Dr. Braden Manns, a kidney specialist at the Faculty of Medicine and a member of the Libin Cardiovascular Institute of Alberta, is unfortunately true. Most recent estimates for Canada show about 5% of the population suffer from diabetes, 20% from hypertension, and about 5-6% struggle with kidney disease, a figure that jumps to 20% in the elderly population.

Current healthcare strategies to deal with chronic disease are limited. Often the patients who are at the highest risk of developing serious illness are not identified before their situation becomes critical. And the problem is worse for those in remote areas who may not have access to appropriate care. It’s because of this that Manns, along with fellow Libin Institute and Faculty of Medicine member Dr. Brenda Hemmelgarn, and Dr. Marcello Tonelli of the University of Alberta, decided they needed to do something different to improve the treatment of chronic illness in Alberta.

Enter the Interdisciplinary Chronic Disease Collaboration (ICDC), a group of researchers from a multitude of medical specialties working together to fight chronic diseases. After forming the ICDC, which is primarily located at the Libin Institute, the trio’s first aim was to invite healthcare policy and decision makers to work closely with them.

“I have enormous confidence in the abilities of these clinical scientists,” says Alberta Health Services senior vice president Deb Gordon, also an ICDC team member. “Their research has been published in an unprecedented number of prestigious journals this year–the New England Journal of Medicine, Circulation, the Canadian Medical Association Journal, the British Medical Journal, two studies in the Journal of the American Medical Association, and two in Lancet. To be published in one of these in a career is an honour. These publications demonstrate the caliber of this team.”

Dr. Francois Charbonneau (left), Heather Conradson (middle), and Dr. Todd Anderson (right) watch as Calgary firefighter Wayne Morris gets a bracial ultrasound.

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

3330 Hospital Drive NW, Calgary, AB, T2N 4N1 www.research4kids.ca

Institute overview The Alberta Children’s Hospital Research Institute (ACHRI) is a multi-disciplinary partnership institute of Alberta Health Services, the Alberta Children’s Hospital Foundation, and the University of Calgary, membership of which 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 upon the discovery and application of knowledge that can optimize the transitions from conception to adulthood, and in so doing contribute to improved health outcomes across the lifespan.

Researchers in ACHRI are organized in five themes with specific research interests:

ACHRI’s primary function is to establish and sustain an optimal research environment, with particular emphasis on the fundamental infrastructure (space, equipment & people) that enables Institute success across the four research pillars: basic/ biomedical; applied/clinical; health services; social, cultural, environmental and population health.

$11,678,945

The total amount of funding the Alberta Children’s Hospital Research Institute (ACHRI) received in 2010 from the Canadian Institutes of Health Research, the Government of Canada’s agency responsible for funding health research. The funding helps support all of ACHRI’s research endeavours.

• Behavior & the Developing Brain - Neurobiological & environmental influences on neurodevelopment and mental health - Neural injury and pathways to repair and recovery • Healthy Living/Injury Prevention & Optimizing Health Outcomes - Identifying and promoting positive family influences on child well-being and development - Preventing childhood obesity and injury - Improving and promoting vaccines - Ensuring use of best evidence - Improving care of acute and chronic childhood injury and illness • Molecular & Genetic Basis of Child Health - Developmental biology of model organisms - Classic human clinical genetics extending to modern genomics • Paediatric Oncology - Drug discovery - high throughput screening and pre-clinical testing - Applied therapeutics - Phase 1 and 2 clinical trials - Best practice research in psychosocial paediatric oncology • Reproductive, Maternal, Fetal & Newborn Health - Reproduction/Placental/Fetal/Neonatal and women’s reproductive (endocrinology and infertility) and nonreproductive (pelvic floor disorders and pain) health Page 12 | 2010 - 2011 Research Report

Dr. Carolyn Emery (right) is studying injury prevention in youth.

Injury prevention starts early

Using diet to help control paediatric epilepsy

Prevention makes perfect for Dr. Willem Meeuwisse, Dr. Carolyn Emery and their team at the University of Calgary’s Sports Injury Prevention Research Centre (SIPRC).

It would take something special to get someone to trade the heat of Arizona for the cold of Calgary, but luckily that “special” something for Dr. Jong Rho happens to be the Alberta Children’s Hospital and the Alberta Children’s Hospital Research Institute.

“Our primary focus is the prevention of youth sport and recreation injuries. We’re really the only centre in the world with that particular focus,” Meeuwisse says.

The SIPRC is an integrated academic and clinical unit that has been providing service to the community of Calgary for almost two decades. Last year, the Centre was awarded a four-year research grant by the International Olympic Committee’s Medical Commission to stimulate further research and collaboration—one of only four research units to earn this award, and the only centre in North America. The funding will enable the Centre to continue their successful sport injury prevention work and will help to significantly expand their research in coming years.

“Sport and recreational are the leading cause of injury in youth and result in a significant public health burden. Long term consequences of injury may include decreased levels of physical activity and early joint osteoarthritis. These injuries are often predictable and preventable,” explains Emery, a member of the Alberta Children’s Hospital Research Institute.

The bigger picture for the SIPRC, which is affiliated with the U of C’s Sport Medicine Centre, is the awareness that being physically active is critically important for health, at any age, but especially for youth. The only side effect is that people do get injuries with participation in sport and recreational activities.

“We’re about reducing the injuries, maintaining the upside of exercise, and minimizing the downside of any injury that can occur. We are hoping to achieve a public-health impact with injury reduction,” Meeuwisse says.

The interdisciplinary research team really came to be with the help of a team development grant by the Canadian Institutes for Health Research in 2006. The program’s focus is now on recruiting more team members around specific projects.

Through the Professorship in Paediatric Rehabilitation, funded through the Alberta Children’s Hospital Foundation, Emery has had the opportunity to build research capacity through interdisciplinary research collaboration in both primary prevention and rehabilitation in paediatrics.

“The impact our research will have in reducing the public health burden of injuries in youth sport and recreation is highly dependent on the community partnerships we have established. The support of organizations such as Hockey Calgary, Calgary Minor Soccer and the Calgary School Board has been critical to the success of our research program.”

“The Alberta Children’s Hospital aspires to be one of the top clinical centres in North America for paediatrics,” says Rho. “The Faculty of Medicine has many strengths, and in particular many departments that are aligned with neurosciences.”

That, coupled with the overwhelming community support for the ACH, helped persuade Dr. Jong Rho to bring his paediatric neuroscience research from Arizona to Alberta. He is the first holder of the Dr. Robert Haslam Chair in Child Neurology at the Faculty of Medicine.

“We can accomplish our goals realistically in the next five to 10 years by turning the ACH into a premiere children’s hospital in North America, and specifically growing paediatric neurosciences into a top tier program for North America.”

Rho has been involved in paediatric research since 1992, with a focus primarily on epilepsy. His current research is on medical treatments for epilepsy and understanding why one-third of patients do not respond to conventional drug therapy. Specifically, Rho and his colleagues’ research focuses on the ketogenic diet, which helps the liver convert fat into ketone bodies that replace glucose as an energy source for our brains. Mysteriously, this change in metabolism helps reduce the frequency of seizures in a child with epilepsy.

“The ultimate goal of understanding dietary treatments is to give us insights into other ways we can control epilepsy, and specifically developing novel drugs or treatments based on that information,” says Rho. While researching a ketogenic diet, Rho and his team discovered the diet and its metabolic substrates have neuroprotective properties, so instead of treating just the symptoms, the diet can essentially protect brain cells from dying.

“If this notion can be validated by additional laboratory and clinical studies, we will then potentially have a readily available therapy that might treat the disease state itself, and not just the symptoms.”

Scan the QR code with your smartphone to learn more about the Alberta Children’s Hospital Research Institute and see their website.

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The McCaig Institute for Bone and Joint Health Dr. Nigel Shrive, Director

3280 Hospital Drive NW , Calgary, AB, T2N 4Z6 www.mccaiginstitute.com

Institute overview The McCaig Institute for Bone & Joint Health maintains the commitment of Mr. J.R. “Bud” McCaig to finding the underlying basis for the development of chronic joint conditions such as osteoarthritis, rheumatoid arthritis and related diseases. With the knowledge gained, the McCaig 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.

While primarily located in the University of Calgary 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, orthopaedic 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 loss of bone and joint health and development of these debilitating chronic diseases and conditions, which affect 15% of Albertans.

The McCaig Institute interacts with the Alberta Bone and Joint Health Institute in relation to health services research. This relationship improves the connectivity provincially which the McCaig Institute is developing in coordination with Alberta Bone and Joint Health Institute. The McCaig Institute is also a focal point for interactions with other independent entities such as the Calgary Bone & Joint Health Program of Alberta Health Services.

The objective of these interactions is to implement the Institute’s successful research to patient populations effectively.

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 the research investment to the benefit of patients and those at risk of becoming patients,” says Dr. Nigel Shrive, director of the McCaig Institute for Bone & Joint Health.

Over the past year, there have been many successes for the McCaig Institute. Last September, thanks to the McCaig Institute’s inaugural fundraiser, called Music in Motion, the Institute was able to purchase new equipment to aid researchers in early detection and diagnosis of arthritis and related rheumatic diseases. This equipment is the first of its kind in Canada and McCaig Institute is one of only three beta test sites for this equipment in the world.

The McCaig Institute is very pleased to have appointed an internationally respected rheumatologist to the Arthur JE Child Chair in rheumatology research. Through the appointment of Dr. John Esdaile, a partnership has been formed with the Arthritis Research Centre for Canada. This collaboration has created the first interprovincial partnership researching a disease entity, thus creating an arthritis research powerhouse in Canada.

“The three independent components (McCaig Institute for Bone & Joint Health, the Calgary Bone & Joint Health Program, and Scan the QR code with your smartphone to learn more about the McCaig Institute and see their website.

Dr. Steven Boyd (left) and Dr. David Hanley in the Bone Imaging Lab.

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Predicting, and fighting, osteoporosis before it happens

First live cartilage shoulder transplant creates new possibilities

Predicting osteoporosis before it happens. Developing treatments to deal with the disease not just after it’s been diagnosed, but to fight it before it occurs. It may seem a little unrealistic, but thanks to researchers at the University of Calgary and some high tech toys, it’s close to being a reality.

An avid soccer player, Jim Chebib has been sidelined by an injured shoulder that has been dislocated eight times in the past five years. Traditional surgery didn’t help, but after becoming the first documented recipient of a live cartilage shoulder transplant in March, the 45-year-old Calgarian hopes to return to the pitch.

Using high-resolution, 3D imaging equipment to measure bone at the wrist and lower leg in healthy volunteers aged 16 to 35, Dr. Steven Boyd, a researcher with the McCaig Institute, was able to examine the changes in bone structure that occur in men and women as they age. By using a mechanical engineering computer modelling method called finite element analysis, researchers were able to predict the changes in bone strength that will occur over time.

“It’s neat to have been part of it,” Chebib says of the groundbreaking surgical procedure. “It sounded like a good solution because it’s all natural and, really, I was happy to have the surgery so I could play soccer healthy again.”

“This could explain why more women experience fractures because of osteoporosis,” says Boyd, also a biomedical engineer at the University of Calgary’s Schulich School of Engineering.

Cartilage is connective tissue found in many parts of the body, and in our joints it works to cushion and protect the bones and creates nearly frictionless movement. However, since cartilage contains no nerve endings or blood supply, it cannot heal on its own if damaged.

Osteoporosis is a bone disease that involves the deterioration of bone tissue, leading to bone fragility and risk of fractures.

According to Osteoporosis Canada, the condition affects two million Canadians and often causes disfigurement and reduction or loss of mobility. Bone health and strength is typically determined by a measurement called bone mineral density. But studying the internal structure of bone is just as important.

“From an engineering perspective, the micro-architecture of bone— how it’s structured and formed—is a good indication of strength,” says Boyd. “It’s like having two houses that contain the same number of bricks. They can have different strengths depending on how those bricks are arranged.”

Researchers believe studying the micro-architecture of bone offers valuable clues when it comes to predicting the onset of osteoporosis and developing better treatments.

“This study has provided the basis of important advances in our understanding of how bone weakens with aging,” says Dr. David Hanley, a professor in the Departments of Medicine, Community Health Sciences, and Oncology at the Faculty of Medicine. “We have also used this imaging equipment and the expertise of Dr. Boyd’s group to study the bone structural and strength response to exciting new treatments of osteoporosis that are being tested in our clinical trials centre.”

10

Number of live donor transplants successfully completed by the Joint Transplantation Program, of which the McCaig Institute is a partner. By detecting cartilage injury early in patients and replacing the damaged region with healthy biological tissue, the development of osteoarthritis and the need for a total joint replacement may be prevented or delayed.

The surgery, performed by orthopaedic surgeon Dr. Mark Heard at Banff Mineral Springs Hospital, is the culmination of extensive research that began two decades ago.

But a team of surgeons and researchers at the McCaig Institute for Bone and Joint Health in Calgary has spent 20 years working with different sources of cartilage and methods of preservation.

They’ve identified a medium that keeps cartilage cells alive for 30 days, and have developed protocols around how to do this. This research could have a significant impact on patients who require cartilage transplants.

“We have longer time frames to screen tissue, match donors with suitable recipients and schedule surgeries,” says Dr. Norman Schachar, director of the Joint Transplantation Program at the McCaig Institute. “With this time frame, we can confirm that at the time of surgery, approximately 90% or greater of the cells in the cartilage are alive, and we have more time to ensure the donor tissue is carefully matched to the recipient.”

In this procedure, surgeons replace damaged cartilage with donor cartilage that is size and location matched. Customized portions of cartilage, attached to bone, are used to restore the joint surface.

The result is nearly seamless healing of the joint as the new tissue is incorporated into the existing bone.

“The surgery restores the joint structure and function, preventing or at least delaying the need for more shoulder surgery,” says Heard.

Several more patients are currently awaiting the same procedure, which is part of an ongoing pilot project. Researchers and surgeons hope the same technique can be used for live tissue transplants in other joints.

“This innovation is a true team effort and the McCaig Institute is on the forefront of this development.”

2010 - 2011 Research Report | Page 15

Southern Alberta Cancer Research Institute Dr. Steve Robbins, Director

Institute overview The landscape of health research in Alberta is changing. The global challenges that face researchers and their work means an integrated, trans-disciplinary approach to cancer research— and the training of future researchers—has never been more important than now. The Southern Alberta Cancer Research Institute (SACRI), a partnership between the University of Calgary Faculty of Medicine and Alberta Health Services-Cancer Care, has identified three scientific divisions to facilitate this strategic approach to research: • Division of Preventive Oncology • Division of Experimental and Cellular Therapeutics • Division for Applied Oncologic Sciences.

Preventive oncology is an emerging research field, and within the Division of Preventive Oncology in SACRI, our established program in the field of molecular cancer epidemiology provides us with an excellent foundation on which to grow.

3280 Hospital Dr. NW, Calgary, AB, T2N 4Z6 www.sacri.ucalgary.ca 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 Faculty of Medicine. 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 supporting foundations.

The 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 for Pediatric Cancers.

The 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 with patient care (distress screening, survivorship, pain management and palliative care).

The fight against cancer is one that is being fought on many fronts and continues to achieve many victories. These include the introduction of preventative measures such as avoiding exposure to cancer risk factors (lifestyle factors, environmental and infectious agents and established carcinogens) through to increased life expectancies as a result of improved treatments from ongoing clinical trials and laboratory-based medical research activities.

Calgary is recognized around the world as one of the centres 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

Page 16 | 2010 - 2011 Research Report

300,000

Number of people taking part in the Canadian Partnership for Tomorrow Project, which the Southern Alberta Cancer Research Institute is a part of.

This Canada-wide study is following the health of participants to find out more about what causes diseases such as cancer, heart disease and other long-term health conditions.

Developing new tools to help determine breast cancer treatments Cancer researchers at Southern Alberta Cancer Research Institute (SACRI) are investigating a new tool to use for the prognosis of breast cancer in patients. This new digital tool will help give patients a more accurate assessment of how abnormal and aggressive their cancer is and help doctors recommend the best treatment options.

Currently, a useful factor for deciding the best treatment strategy for early-stage breast cancer is tumour grade, a score assigned by a pathologist based on how abnormal cancer cells from a patient tissue sample look under the microscope. However, tumour grade is somewhat subjective and can vary between pathologists. Hence the need for more objective methods to assess cancer tissue, which could improve risk assessment and therapeutic decisions.

Using a mathematical computer program developed at the Faculty of Medicine, Mauro Tambasco, PhD, and his team used fractal dimension analysis to quantitatively assess the degree of abnormality and aggressiveness of breast cancer tumours obtained through biopsy. Fractal analysis of images of breast tissue specimens provides a numeric description of tumour growth patterns as a continuous number between 1 and 2. This number, the fractal dimension, is an objective and reproducible measure of the complexity of the tissue architecture of the biopsy specimen. The higher the number, the more abnormal the tissue is.

According to the team’s published study, this novel method of analysis is more accurate and objective than pathological grade.

“This new technology is not meant to replace pathologists, but is just a new digital tool for them to use” says Tambasco, a SACRI member.

Researchers say they will continue to study this new digital method and hope in the next few years that it could become another tool used in the clinical setting.

The retrospective study analysed tissue specimens from 379 breast cancer patients and the findings were published in the January 2011 edition of the Journal of Translational Medicine.

Using fitness to fight breast cancer Dr. Christine Friedenreich is at it again.

For the past 17 years, Friedenreich has studied the role physical activity has in cancer prevention and control. Her widely successful research trial known as the Alberta Physical Activity and Breast Cancer Prevention Trial (ALPHA Trial), wrapped up in 2006 after studying well over 300 women. Now she’s already started a sequel trial to ALPHA Trial, cleverly dubbed the BETA Trial—the Breast Cancer and Exercise Trial in Alberta.

“Essentially what we’re coming up with is some clear evidence about what dose of activity women need to do to reduce their risk of breast cancer,” explains Friedenreich, a member of the Southern Alberta Cancer Research Institute.

Beginning in July 2003, Friedenreich’s ALPHA Trial sought to examine the physiologic changes that occur in a woman’s body when she begins exercising and the possible relation with her risk of getting breast cancer. The trial introduced a one-year exercise program to 320 women living a moderately sedentary lifestyle. All participants had to be postmenopausal women, aged 50-74, without a history of cancer.

“Physical activity definitely helps reduce the risk of getting cancer and once someone has cancer, exercise can be used to help cope with the treatment and help with the rehabilitation, and also to improve their quality of life and survival afterwards,” observes Friedenreich.

Now with the BETA Trial, which began in June 2010, Friedenreich is focused on the amount of exercise needed to effectively reduce the breast cancer risk in postmenopausal women. The trial will include 330 women who will be divided into two groups: one that will complete a moderate volume of aerobic exercise (150 minutes per week), and another that will complete a high volume of exercise (300 minutes per week).

“With the ALPHA Trial we found that physical activity decreased body fat and hormone levels thought to be involved in the pathways leading to breast cancer risk,” says Friedenreich.

“Now with the BETA Trial, we want to look at determining more precisely what dose of exercise is required to influence these biological mechanisms. Ultimately this research will provide solid data on the type and amount of exercise that is required to reduce cancer risk.”

Dr. Mauro Tambasco analyzes breast tissue samples on his computer.

2010 - 2011 Research Report | Page 17

Calgary Institute for Population and Public Health Dr. William Ghali, Scientific Director

Institute overview Removing inequities in population health and improving health care delivery requires trans-disciplinary approaches to understanding the links between health determinants and health outcomes. Through evidence-informed interventions we can create positive new trends in health that impact Canadians and others around the world in a visible and meaningful way.

The Calgary Institute for Population and Public Health (CIPPH) brings together over 230 of Alberta’s researchers and health professionals—drawn from multiple university faculties and schools, health service providers, government agencies and community organizations. Their collective vision is to devise innovative responses to our most pressing public health problems.

The Institute not only fosters the development of transdisciplinary research, but also acts to transfer the latest and best knowledge between the scientific and public communities, thereby ensuring rapid assimilation and practical application of scientific knowledge to improve health outcomes. In fulfilling its role as an agent of innovation and broker in the transfer of knowledge, the Institute sponsors collaborative partnerships among individuals, teams and organizations, giving voice to their collective vision and intent.

Scan the QR code with your smartphone to learn more about Calgary Institute for Population and Public Health and see their website.

3280 Hospital Drive NW, Calgary, AB, T2N 4Z6 www.ucalgary.ca/cipph | cipph@ucalgary.ca Drinking alcohol in moderation protects against heart disease If you’re the type who enjoys a glass of wine after a long day we’ve got good news for you; that glass of vino isn’t just helping you relax, it’s also helping you avoid heart disease.

Individuals who drink alcohol in moderation (about one drink a day or less) are 14-25% less likely to develop heart disease compared to those who drink no alcohol at all, finds research led

by Dr. William Ghali, published in the British Medical Journal.

A number of previous studies have concluded that moderate alcohol consumption has been associated with a decrease in heart disease, but that research was out-of-date and in need of new material. Ghali says his team’s research is the most comprehensive to date.

Ghali and colleagues reviewed 84 studies of alcohol consumption and heart disease. They compared alcohol drinkers with nondrinkers and their outcomes in relation to heart disease, death from heart disease, incidences of stroke and death from having a stroke.

In a companion study led by Dr. Susan Brien of the Faculty of Medicine, she and her colleagues reviewed 63 studies and investigated alcohol consumption with known physical markers for heart disease such as cholesterol, levels of inflammation, fat cells and the condition of blood vessels. They also assessed the impact of the type of alcohol consumed (wine, beer and spirits).

Interestingly, Brien’s research concludes that it is the alcohol content that provides the health benefit, not the type of alcoholic beverage (wine, beer or spirits) that is consumed.

Ghali believes the debate between the impact of alcohol on heart disease should now centre on how to integrate this evidence into clinical practice and public health messages.

“There may now be an impetus to better communicate to the public that alcohol, in moderation, may have overall health benefits that outweigh the risks in selected subsets of patients. Any such strategy would need to be accompanied by rigorous study and oversight of impacts.”

Page 18 | 2010 - 2011 Research Report

Want a healthy lifestyle? Better get a pet You love your little Fidos, Franks, or whatever you call you pet pooch, and it turns out that bond you have with your pet is good for your health.

“Pets are increasingly important in the lives of Canadians—more than half of Canadian households have a pet. What we see here is a significant public health opportunity, and we want to leverage this powerful cultural trend towards better human health.”

Dr. Melanie Rock’s research is definitely interesting, especially if you are a pet owner. In her interviews with pet owners, Rock has found people tend to blur the lines between what they learn about their dog or cat’s health and their own health, including physical activity, diet, and stress management.

Calgarian Daniela Trnka, a participant in Rock’s study, was diagnosed with Type 1 diabetes 20 years ago. When she saw signs of diabetes in her Siberian Husky, Cooper, she pulled out her own blood sugar testing kit to investigate his blood sugar levels. “His blood sugar was 22 so I knew right away that it was diabetes.” Cooper’s veterinarian confirmed the diagnosis, and Cooper has been taking insulin medication ever since.

“Cooper brings a smile to my face every morning. Having to test his blood sugar gets me out of bed to test my own levels,” admits Trnka. “On a cold, windy day he gets me outside in the fresh air because I know the exercise is good for him. And that’s good for me too.”

The research included interviews with 16 pet owners, six veterinarians, a mental health counselor, and a pharmacist.

Rock’s team finds that because people care deeply about their pets’ health, they take seriously how best to care for them, and take what their vet recommends to heart.

“Pet care is an important way that people are acquiring and processing information about health,” says Rock, a member of the Calgary Institute for Population and Public Health.

Rock has also conducted further research into whether dog ownership influences summer and winter patterns of neighbourhood-based walking among adults living in Calgary.

Results of this study will be released this year.

44%

Increase in number of researchers the Calgary Institute for Population and Public Health has achieved in 2010.

This brings the total number of researchers to 236, individuals who contribute to the Institute’s agenda of research, education, knowledge translation and community engagement to improve the health and well-being of all.

Daniela Trnka (left) with her dog Cooper, and Dr. Melanie Rock.

2010 - 2011 Research Report | Page 19

Centre for Advanced Technologies Dr. John Reynolds, Director

AT

CENTRE FOR ADVANCED TECHNOLOGIES

5E23, TRW Building 3280 Hospital Drive NW, Calgary, AB, T2N 4Z6 cat.ucalgary.ca | macklon@ucalgary.ca

Institute 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.

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

90 years

Length of time before researchers at the University of Calgary discovered how alum, an immune booster present in almost all vaccines, works to induce antibody responses. The discovery was made possible through a technique UCalgary researchers developed using atomic force microscopy to produce 3D images of the surface of an atom.

• 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.

“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.

Page 20 | 2010 - 2011 Research Report

Scan the QR code with your smartphone for links to all the services available to researchers through the Centre for Advanced Technologies.

New technology holds potential for major advances in medicine For Dr. Matthias Amrein it all began in Zurich in the lab of Nobel Laureate Heinrich Rohrer. Rohrer was one of the brains behind the development of the atomic force microscope (AFM); a microscope with a very fine probe designed to scan surfaces atom by atom and produce three-dimensional images. Amrein, who was lucky enough to get a position in the inventor’s lab, was the first person to successfully apply this new technology to a biological problem.

Now at the University of Calgary, Amrein, together with immunologist Dr. Yan Shi, have developed a new and powerful way to use AFM. Instead of using the microscope to generate images, they are using it as a spectrometer, measuring the interaction of living cells with specific particles attached to the microscope’s probe. “When a particle comes in contact with a cell, it can trigger a signaling cascade inside the cell,” explains Amrein. “If we block the right signaling pathway, the cell will let go of the particle. If we block the wrong signaling pathway, the particle will stick. This is how we can analyze cellular activation.”

Amrein and Shi are promoting broad use of the technology by the local research community through the Faculty of Medicine’s Centre for Advanced Technologies. Labs are looking at problems ranging from how a malaria-infected red blood cell interacts with blood vessels to how inhaled particles interact with the alveoli in the lungs. A recent paper in Nature Medicine focused on how alum, a crystal used as a vaccine adjuvant, interacts with the immune system.

“We believe we have widened the scope of this technology to now include fundamental problems in medicine,” says Amrein.

He and his colleagues are now looking at the potential for commercialization of this new technique. “By making it commercially available we can help other labs to do significant work,” says the researcher. “That is our vision; we believe that this technology can do great things for medicine.”

Making research easier around the world Stories about major advances in medical research don’t often include the challenges that researchers face behind the scenes.

Colleen Geary-Joo, manager of Transgenic Services at the Faculty of Medicine, a unit which develops research models of genetically modified mice, knows first-hand about some of the hurdles researchers deal with on a daily basis.

“Researchers have been working with transgenic mice for decades, but sharing mice between research institutions can still be difficult,” says Geary-Joo. In order to prevent the spread of disease, research facilities importing mice often demand detailed health documentation. And mice imported from other institutions can be subject to quarantine, causing significant delays.

To solve these problems, transgenic research facilities around the world are working more and more with mouse embryos. Embryo rederivation, a technique in which embryos are implanted into disease-free surrogate females, is an effective and virtually foolproof way to eliminate infectious mouse pathogens from any colony. In most cases, shipping embryos is also cheaper and easier.

Embryo rederivation is not a new idea. In the last 10 years, the lab at the University of Calgary has rederived over 55 strains of transgenic mice. What is new is that more facilities have the necessary skill and experience to work with embryos, and the demand for embryos is increasing. With years of experience behind it, the Faculty of Medicine is extremely well positioned to handle this demand.

“We have the technical ability and experience to both harvest and ship, as well as receive and implant embryos,” explains GearyJoo. The lab also has a cryo-preservation program that allows investigators to store important strains. Just recently, mouse pups were born from a strain that had been frozen for 10 years.

All this makes it easier for researchers around the world to focus on the real goal: making important discoveries that can lead to advances in healthcare.

Dr. Matthias Amrein works with an atomic force microscope.

2010 - 2011 Research Report | Page 21

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

3280 Hospital Drive NW, Calgary, AB, T2N 4Z6 www.ucalgary.ca/cccr

Institute 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 University of Calgary Faculty of Medicine and it’s research institutes and other faculties at the University of Calgary.

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.

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 finally, developing new medical solutions for patients.

In 2010, 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 at the Faculty of Medicine, 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. An agreement between the six provincial ethics boards has been made in which a move towards a single provincial electronic platform for submission of research proposals for ethics review is underway. 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.

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Scan the QR code with your smartphone to see how Dr. Remo Panaccione helped a speed skater on the Canadian national team deal with inflammatory bowel disease.

Developing drugs to treat inflammatory bowel disease For Dr. Remo Panaccione, his passion for drug development begins with the patients. For the last decade, Panaccione has been at the forefront of 42 clinical trials testing drug therapies for ulcerative colitis and Crohn’s disease, the two most common conditions that make up the inflammatory bowel disease (IBD) family.

“It’s all about the patient, and we’re trying to give the patient the best opportunity to have a favourable outcome,” says Panaccione, director of the Inflammatory Bowel Disease Clinic at the Faculty of Medicine. “They are the ones who potentially benefit as they’re receiving a therapeutic agent that is not available on the market, and one they couldn’t get outside of the Centre.”

The Centre Panaccione is speaking of is the Calgary Centre for Clinical Research, a showpiece facility at the Faculty of Medicine.

In particular, the Centre houses the Heritage Medical Research Clinic, where the IBD clinical trials have been conducted.

“These are drugs that have changed the way we treat ulcerative colitis and Crohn’s disease, and we examined all of them right here,” says Panaccione.

Improving treatment options for IBD patients is always a priority for the entire Division of Gastroenterology at the Faculty of Medicine. And there is no shortage of patients in Alberta; our province has one of the highest IBD rates in the world. For Panaccione that fact is bittersweet.

“Because we have so many patients, there is always interest for participation in the clinical trials. But I think the sad thing is there are still many patients who don’t know these trials may be available to them, and they may be at the point where they have finished standard therapy and they feel they don’t have many options. It’s one of our ongoing goals to make these clinical trials accessible to everyone who has the disease.”

“A decade ago we were just another recruiting site where clinical trial leaders would say ‘we need two or three patients from you’,” recalls Panaccione. “Now as our expertise and our international reputation have grown, they come to us before the trial has even started to say ‘we have this drug, we think it may be useful in IBD, can we meet and discuss what you think the potential is for this?’. So our role has really expanded globally and now we help shape these clinical trials.”

Their role is also crucial. Less than 1% of IBD drugs that go through the clinical trial process actually make it to market; of the 42 clinical trials Panaccione has been involved with, only five received approval for public use. Of those five drugs, however, three were for the treatment of Crohn’s disease and represent the only drugs for this disease to reach the market in the last decade.

42

Number of clinical trials testing drug therapies for ulcerative colitis and Crohn’s disease Dr. Remo Panaccione has worked on in the last decade. During that time only three drugs have been approved for patient use for Crohn’s disease in the world; all three were tested by Dr. Panaccione.

Dr. Remo Panaccione in the Heritage Medical Research Clinic.

2010 - 2011 Research Report | Page 23

Graduate Science Education Dr. Frans van der Hoorn, Associate Dean

3330 Hospital Drive NW, Calgary, AB, T2N 4N1 www.medicine.ucalgary.ca/grad medgse@ucalgary.ca

Institute overview 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 research-intensive environment at the Faculty of Medicine, 585 graduate students were registered throughout the 2010 year—34% of them international students—in the masters (MSc, MDSC, 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: • Biochemistry & Molecular Biology • Biomedical Technology • Cardiovascular & Respiratory Sciences • Community Health Sciences • Gastrointestinal Sciences • Immunology • Microbiology & Infectious Diseases • Medical Science, with specializations in: - Cancer Biology

the quality of all programs to ensure optimal student education and experience. In 2010, our graduate programs convocated 96 students: 21 MBT, 6 MDCS, 40 MSc and 29 PhD. Of note, 10 of these students graduated with joint degrees: 2 MBT/MBA, 5 MD/ MSc and 3 MD/PhD. “Graduate education depends critically on the personal mentoring of the student by a faculty member, which ensures a high quality education. Over 160 faculty members are involved in supervision with 315 serving on supervisory committees. The one-on-one instruction is supplemented by over 80 intensive graduate courses in the Faculty of Medicine,” says Dr. Frans van der Hoorn, associate dean, Graduate Science Education.

In addition, over 35 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 health care delivery programs.

Over 43% of our graduate students received competitive awards, scholarships and/or prizes from federal agencies including 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 and the Alberta Cancer Foundation. This has brought in close to $2.8 million in support of research.

- Critical Care Medicine - Joint Injury & Arthritis - Medical Education - Molecular & Medical Genetics - Mountain Medicine & 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

Page 24 | 2010 - 2011 Research Report

Scan the QR code with your smartphone to learn more about Graduate Science Education at the Faculty of Medicine and see their website.

Unraveling the secrets of brain function

Fighting disease in the lab and the clinic

While many people probably know the brain consists of billions of cells called neurons, they may not know that each brain cell connects with thousands of others. Most people’s understanding of the brain is very basic; good thing we have neuroscientists to figure out how things in the brain work and why.

Society should be thankful for people like Braedon McDonald. The budding researcher is not just a regular graduate student; enrolled in the Leaders in Medicine program, McDonald, who is studying immunology, is working towards both his MD and PhD at the same time. But the double workload isn’t a burden as McDonald sees it.

That’s where Karl Iremonger comes in. The former Faculty of Medicine neuroscience student is currently continuing his research training in New Zealand in a world-renowned research lab where they are using sophisticated microscopes to visualize changes in activity in small regions of brain cells known as dendrites.

“It’s truly a privilege be a part of the Leader’s in Medicine MD/ PhD program and have the opportunity to be involved in both research and medicine. Although it requires long hours of work and dedication to extra years of training, I enjoy every minute.”

“I study how the connections between brain cells change in response to different patterns of brain activity and different chemical messengers normally released in the brain. Because brain cells are so complex, there is still much to discover about these tiny cells,” Iremonger says of his chosen path. “This sense of discovery is one of the reasons I have chosen to do neuroscience research.”

The benefits of Iremonger’s research is more long-term than immediate but the research is still very important—if not crucial, to neurology.

“The brain is similar to the engine in a car. You can’t easily fix it unless you know how it’s put together and how it works when it’s functioning properly,” he explains. “We won’t be able to effectively treat all neurological diseases until we have a much better understanding of how the brain functions in healthy individuals.”

Iremonger is a past recipient of the prestigious Dr. Lionel E. McLeod Health Research Scholarship, and trained in the lab of Dr. Jaideep Bains at the Faculty of Medicine. It was there he studied how nerve cells in particular regions of the brain cope with stress and injury.

The program allows students to complete both their doctor of medicine (MD) degree and their doctoral (PhD) degree at the same time. McDonald, being a past recipient of the prestigious Dr. Lionel E. McLeod Research Scholarship—an award given to academically superior students—is a perfect candidate to take one not one but two degrees.

“To me both scientific research and clinical medicine are very interesting and fulfilling, and they complement each other nicely.”

Currently, McDonald is working towards understanding how cells of the immune system detect and respond to infectious versus non-infectious insults. Basically, understanding and identifying the differences between how the immune system responds to tissue injuries versus infections may open the door for new antiinflammatory drugs, which is good news for everyone.

“The ability of the immune system to mount inflammatory responses is essential to protect us from infections, but the body also generates inflammation in response to non-infectious insults, such as tissue injury,” he explains. “These drugs would selectively inhibit pathologic inflammation without affecting the body’s ability to fight infection.”

So when does he expect to complete his PhD and his MD studies?

“As soon as I can figure out how to make the days longer than 24 hours.”

585

Number of graduate students at the Faculty of Medicine registered in masters (MSc, MDSC, MBT) and doctoral (PhD) programs in 2010, carrying out innovative research with some of the best researcher in their fields. 34% of these are international students.

Braedon McDonald is working towards both his MD and his PhD as part of the Leaders in Medicine program.

2010 - 2011 Research Report | Page 25

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 eight years ago, the total endowment value now represents over $150 million. 10 years ago we had one endowed Research Chair, today we have 48 Chairs and Professorships.

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

Brenda Strafford Foundation Chair in Alzheimer Research Dr. Minh Dang Nguyen

Alberta Cancer Foundation Weekend to End Women’s Cancer Chair in Breast Cancer Research Vacant

Brenda Strafford Foundation Chair in Geriatric Medicine Dr. David Hogan

Alberta Children’s Hospital Foundation Chair in Pediatric Research Dr. Brent Scott Alberta Children’s Hospital Foundation Cuthbertson and Fischer Chair in Pediatric Mental Health Dr. Frank MacMaster Alberta Children’s Hospital Foundation Professorship in Child Health and Wellness Dr. Brent Hagel Alberta Children’s Hospital Foundation Professorship in Pediatric Rehabilitation Medicine Dr. Carolyn Emery Alberta Children’s Hospital Foundation Dr. Robert Haslam Chair in Child Neurology Dr. Jong Rho 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 Dr. John Esdaile AstraZeneca Chair in Cardiovascular Health Promotion and Disease Prevention Vacant

Calvin, Phoebe and Joan Snyder Chair in Critical Care Research Dr. Paul Kubes Calgary Foundation - Grace Glaum Professorship in Arthritis Research Dr. David Hart Campbell McLaurin Chair for Hearing Deficiencies Dr. Jos Eggermont Cal Wenzel Chair in Hepatology Dr. Mark Swain Crohn’s & Colitis Foundation of Canada Chair in Inflammatory Bowel Disease Research Dr. Keith Sharkey Enbridge Research Chair in Psychosocial Oncology Dr. Linda Carlson Engineered Air Chair in Cancer Research Dr. Susan Lees-Miller Dr. Frank Leblanc Chair in Spinal Cord Research Dr. Peter Stys Fraser Mustard Chair in Childhood Development Dr. Margaret Clarke GSK Professorship in Inflammatory Lung Disease Dr. Richard Leigh Heart and Stroke Foundation of Alberta, NWT & Nunavut Chair of Cardiovascular Research Dr. Henry Duff Heart and Stroke Foundation of Alberta, NWT & Nunavut Chair in Stroke Research Dr. Andrew Demchuk

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Heart and Stroke Foundation of Alberta, NWT & Nunavut Professorship in Stroke Research Dr. Michael Hill Hopewell Professorship in Brain Imaging Dr. Richard Frayne Hopewell Professorship in Clinical Neurosciences Research Dr. Sam Wiebe Husky Energy Alberta Children’s Hospital Foundation Chair in Child and Maternal Health Dr. Brent Scott Jessie Boden Lloyd Professorship in Immunology Research Dr. Christopher Mody

N.B. Hershfield Professorship in Therapeutic Endoscopy Vacant Ohlson Family Professorship in Head and Neck Surgery Dr. Joseph Dort Parkinson’s Society of Southern Alberta/Suter Professorship in Parkinson’s Research Dr. Bin Hu Roy and Joan Allen Professorship in Sight Research Dr. Torben Bech-Hansen Dr. Lloyd Sutherland Professorship in IBD/GI Research Vacant

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

Svare Professorship in Health Economics Dr. Herbert Emery

Julia McFarlane Chair in Diabetes Research Dr. Pere Santamaria

Westaim – ASRA Chair in Bacterial Biofilm Research Dr. Shawn Lewenza

Kids Cancer Care Foundation Alberta Children’s Hospital Chair in Pediatric Oncology Vacant Kinsmen Chair in Pediatric Neurosciences Vacant Lance Armstrong Research Chair in Molecular Cancer Epidemiology Dr. Hans Vogel Markin Chair in Health and Society Dr. Penelope Hawe McCaig Professorship in Joint Injury and Arthritis Dr. Cyril Frank Merck Frosst Chair / Professorship in Cardiovascular Research Vacant Novartis Chair in Schizophrenia Research Dr. Jean Addington

Financial Statements 2009-10 Federal Government Tri-Council (CIHR, NSERC, SSHRC) Canada Foundation for Innovation (CFI) Other Federal Government Canada Research Chair (Funded by CIHR)

Total Federal Government

30,309,607.44 3,080,628.48 1,692,477.91 4,550,000.00

39,632,713.83

Albera Provincial Government Alberta Innovates-Health Solutions Provincial Research Envelopes Alberta Health Services (AHS) - includes Cancer Board Other Alberta Provincial Government

Total Alberta Provincial Government Other Canadian Universities and Hospitals

22,336,702.11 4,164,776.00 11,368,516.32 9,535,010.31

47,405,004.74 5,342,357.28

Foreign Sources U.S.A. Sources (Public and Private) Other Foreign Sources

Total Foreign Sources Business

8,664,567.59 720,475.40

9,385,042.99 8,752,425.48

Non-Profit Organizations Provincial National

Total Non-Profit Organizations

2,469,659.51 1,311,449.03

3,781,108.54

Foundations National Provincial

8,910,547.58 6,234,749.56

Total Foundations

15,145,297.14

Endowments, Individuals and Internal Sources

16,674,003.15

Total Revenue

$146,117,953.15

2010 - 2011 Research Report | Page 27