Innovation Improving Health -- 2009-10 Research Report

Innovation Improving Health 2009-2010 Research Report

Editor Kyle Glennie

Contributors Marta Cyperling Kyle Glennie Krista Goheen Gen Handley Jordanna Heller Sheelagh Matthews Ian Weetman

Photography Carlos Amat Kelly Budd John Gaucher Robin Kuniski Janelle Pan Bruce Perrault

Concept and Design Kelly Budd, Radius Creative

Thank you to all institute and centre staff for their contributions

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2009-2010 Research Report

Message from the Senior Associate Dean, Research

Hotchkiss Brain Institute

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

5 6 8 10

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

Libin Cardiovascular Institute of Alberta

12

McCaig Institute for Bone and Joint Health

14

Southern Alberta Cancer Research Institute

16

Calgary Institute for Population and Public Health

18

Centre for Advanced Technologies

Calgary Centre for Clinical Research

22

Graduate Science Education

24

Financial Statements 2008 - 2009

26

20

2009-2010 Research Report | Page 3

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Innovation improving health When the Faculty of Medicine created its research strategic plan in 2009, advancing health and wellness was identified as our main priority. As one of the most prominent societal issues in Canada, it is our duty as a Faculty not only to educate future physicians and scientists, but to also improve the health of our communities, now and in the future. We must continue our strong fundamental work in science and biomedical research, but also translate discovery in the laboratory to clinical practice and to the benefit of society as a whole. In some cases, fundamental molecular studies lead to clinical investigations of disease processes that, in turn, create novel therapies and biomedical engineering solutions to health problems. In other cases, studies of population health and health economics result in improved health policy, promotion and delivery for all Albertans.

In the past year the creative imaginations of our researchers have led to innovations across the health research spectrum. Whether it be research at a genome-scale, like the work of Mark Bieda, PhD, who is uncovering how information encoded in our DNA comes to life in a cell (page 10), or research conducted using human tissue samples, like that of Neil Duncan, PhD (page 14), we innovate to improve health. With the creation of the Regeneration Unit in Neurobiology, led by Dr. Doug Zochodne, our scientists and physicians will develop new therapies and biomedical engineering solutions aimed at reconnecting damaged or broken ner ve fibres (page 6). These are just a few of our ongoing endeavours– more are outlined in this report.

As our research priorities evolve so do our research institutes. The Institute for Child and Maternal Health has transformed into the Alberta Children’s Hospital Research Institute for Child and Maternal Health (ACHRI). By bringing together basic biomedical scientists and clinical scientists, ACHRI is building on its vision of “healthy babies, healthy children and youth, healthy lives”. We have also seen the creation of the Calgary Institute for Population and Public Health in the last year. With over 160 members from a wide range of disciplines including medicine, nursing, social work and social sciences, the Institute strives to improve health services and affect public policy. This brings our complement of research institutes to seven and focuses our priorities on exciting, innovative and achievable goals.

But even with our entire faculty working with common purpose, many external collaborations are still needed to improve the health of our communities. With this in mind we are committed to growing and maintaining strong relationships with the rest of the University of Calgary, with other Alberta universities, and with Alberta Health Services. Our researchers in the Faculty of Medicine have teamed up with their colleagues throughout the province and, thanks to our partnerships with Alberta Health Services, we effectively translate our joint research into tangible health improvements for the community.

Our utmost appreciation and thanks go 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 provide the financial support that drives our research, and without them none of our achievements would be possible.

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

2009 marked the fifth anniversary of the Hotchkiss Brain Institute (HBI). In just five years, the HBI has established itself as a leading centre for neurological and mental health research, education and innovation.

This past year, the HBI created a new strategic framework that will guide the Institute’s areas of focus for the next five years. This framework outlines three foundational research priority themes that represent areas of both strength and emerging potential in research, education and the translation of discoveries into improved health: • Axon biology and regeneration, applied to spinal cord and nerve injury and Multiple Sclerosis • Cerebral blood flow regulation, applied to stroke and vascular dementia; and, • Synaptic transmission and neural systems, applied to depression and psychosis.

Within these themes, working with and learning from the HBI’s scientists are the students and fellows that represent the next generation of neurological and mental health researchers.

The HBI is home to more than 200 MSc, PhD and post doctoral trainees, primarily located within the Faculty of Medicine. In the past year, more than 30 HBI trainees received competitive funding from external agencies.

In addition, the HBI currently supports 14 trainees with internal awards, including the HBI Postdoctoral

Fellowship Award, the HBI Resident Scientist Award, the Denyse Lajoie-Lake Fellowship, and the Dr. T. Chen Fong Doctoral Scholarship in Neuroscience.

Undergraduate students looking towards a future in the neurosciences need look no further than the University of Calgary’s Bachelor of Science in Neuroscience program.

The creation of this new and innovative honours program was led by the HBI in collaboration with three faculties (Medicine, Science and Social Sciences). Enhanced educational opportunities for students in the program have been made possible with a $1 million donation to the Hotchkiss Brain Institute from the Kahanoff Foundation.

The HBI also reaches out to high school students through programs such as the Heritage Youth Researcher Summer (HYRS) Program. In 2009, 13 of the 22 HYRS students selected to participate in the program from southern Alberta had the opportunity to spend six weeks gaining hands-on experience in HBI laboratories.

The outstanding success of the Hotchkiss Brain Institute over the last five years is due in large part to the outstanding efforts and contributions of its researchers.

The trainees working with HBI members, who represent the future of neurological and mental health research, will continue to shape the success of the HBI, helping to maintain the Institute as a leader in neuroscience research, education and innovation.

Jaideep Bains, PhD, whose research seeks to understand how our brains respond to stress.

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Identifying how our brains respond to stress

Engineering the impossible

Chronic stress takes a physical and emotional toll on our bodies, and scientists are working on piecing together a medical puzzle to understand how we respond to stress at the cellular level in the brain.

It’s one of modern medicine’s most perplexing, untreatable problems: the failure of injured spinal cord and brain nerve fibres to regenerate or reconnect. But with the Hotchkiss Brain Institute’s (HBI) Regeneration Unit in Neurobiology nearing completion, HBI researchers will soon have the tools to tackle this problem head-on.

Being able to quickly and successfully respond to stress is essential for survival. Using a rat model, Jaideep Bains, PhD, a University of Calgary scientist and his team of researchers at the Hotchkiss Brain Institute have discovered that neurons in the hypothalamus, the brain’s command centre for stress responses, interpret ‘off’ chemical signals as ‘on’ chemical signals when stress is perceived.

“It’s as if the brakes in your car are now acting to speed up the vehicle, rather than slow it down.” says Bains.

This unexpected finding was published in the March 1st, 2009 online edition of Nature Neuroscience.

Normally, neurons receive different chemical signals that tell them to either switch on or switch off. The off signal, or the ‘brake’, only works if the chloride ion levels in the cells are kept to a minimum. This is accomplished by a protein, known as KCC2. What Bains and colleagues have shown is that stress turns down the activity of KCC2, thus removing the ability of the brake, a chemical known as GABA, to work properly. A loss of the brain’s ability to slow down may explain some of the harmful, emotional consequences of stress.

“This opens entirely new and quite unexpected avenues for controlling stress responses” says Yves De Koninck, PhD, president-elect of the Canadian Association for Neuroscience and professor of Psychiatr y at Laval University.

“I was fascinated when I learned of this work,” says Jane Stewart, PhD a behavioural neuroscientist at Concordia University. “Until now, it has not been clear how the neuroendocrine stress response was activated by external stressors. These findings may lead to a better understanding of the changes in sensitivity to stress that result from chronic exposure.”

The research was supported by the Canadian Institutes of Health Research. Bains is an Alberta Heritage Foundation for Medical Research scholar (now Alberta Innovates–Health Solutions) and an associate professor in the Department of Physiology and Biophysics.

50,000

“The new unit is getting set up and the plans are very promising,” says Dr. Doug Zochodne, co-leader of the HBI’s Regeneration node and professor in the Department of Clinical Neurosciences. “RUN should be completed by late-Spring or early-Summer, allowing us to ramp up ongoing work in new and innovative ways.”

With RUN’s specialized laser microscopy suites and other novel facilities, investigators at the Faculty of Medicine will be able to develop new therapies and biomedical engineering solutions for reconnecting broken and damaged nerve fibres, or axons. When axons are broken, they quickly degenerate and must be regrown or regenerated to establish the connection again.

RUN will allow more research to be completed on axon regeneration, but with a particular focus on treatments for people with neurological injury and disease. Also included in RUN’s plan is the use of novel technologies to track living, re-growing axons; to microdissect amounts of selective tissues for analysis; and for ultra highimaging resolution of biological tissues.

Zochodne’s primary area of research is axon regeneration following peripheral nerve damage or disease. These are common clinical problems that are seen, for example, at the University of Calgary Neuromuscular clinic, but for which no therapies are available to reverse the damage.

The upgraded technologies will also be applied toward understanding spinal cord injury. The overall idea is to test strategies that improve regeneration in isolated neurons, injured nerves and spinal cords of disease models with an ultimate goal to translate the findings into human clinical trials.

“The identification of new approaches toward nerve regeneration will have a substantial impact on the quality of life for people with neurological damage,” Zochodne says. “I think RUN is incredibly important for this reason.”

The laser microscopy suites are the result of $1.3 million in funding from the Canadian Foundation for Innovation’s Leading Edge Fund, another $1.3 million from the Alberta Science and Research Investments Program, and $600,000 from HBI and other sources–a total of $3.2 million in funding.

Approximate number of Canadians that suffer from stroke each year. Advancing stroke care and rehabilitation is the central focus of the HBI’s cerebral blood flow regulation research, one of the key priorities of the Institute’s strategic framework.

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The Calvin, Phoebe and Joan Snyder Institute of Infection, Immunity and Inflammation Dr. Paul Kubes, Director 3280 Hospital Drive NW, Calgary, AB, T2N 4Z6 www.iii.ucalgary.ca cgelette@ucalgary.ca

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-I diabetes, inflammatory bowel disease (IBD), 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.

With 14 Canada Research Chairs and six endowed chairs (three more in progress), members of the Snyder Institute can take pride in our accomplishments. These include: • Successfully competing for an unprecedented three Canadian Foundation for Innovation (CFI) grants; one in the area of inflammation, one in the area of virology (together with the University of Alberta) and one in the area of water (together with the University of Calgary Department of Microbiology and Infectious Diseases, the Schulich School of Engineering, and the City of Calgary). The total value of these grants is close to $25 million.

• Successfully competing for three Alberta Heritage Foundation for Medical Research (now Alberta Innovates–Health Solutions) Interdisciplinary Team Grants; one in the area of children vaccines, one in the area of sepsis and one in the area of IBD. The total value of these grants is close to $15 million.

The annual research funding of over $32 million at the Snyder Institute represents the Institute’s commitment to basic and translational research in its focused disease area, and impacts the lives of those suffering from these debilitating diseases. Along with these incredible successes, the Snyder Institute also features four initiatives that enable both basic and clinical research: Page 8 | 2009-2010 Research Report

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

2) Live Cell Imaging Facility This well established core facility–funded by the Canada Research Chairs Program, the CFI and the Canadian Institutes of Health Research (CIHR)– provides training in imaging all aspects of the immune response from single cells in-vitro, to in-vivo imaging of the immune system and infections in the brain, liver, skin, muscle and other organs.

3) 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.

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.

With a $1 million donation from the Brister Foundation, the Experimental Respiratory Suite is equipped with modern radiographic and diagnostic technology.

This facility allows researchers to perform human studies ranging from investigation into basic disease processes, to testing of new drugs.

$32 Million Total amount of funding the Snyder Institute used in 2009 for research.

This figure represents the Institute’s commitment to innovate new treatments for health issues such as cystic fibrosis, type-I diabetes, inflammator y bowel disease, chronic obstructive pulmonar y disease, and asthma.

Director of the Snyder Institute elected to the Royal Society of Canada This fall the Royal Society of Canada (RSC), Canada’s oldest and most prestigious academic body, elected Paul Kubes, PhD, director of the Calvin, Phoebe and Joan Snyder Institute of Infection, Immunity and Inflammation (Snyder Institute) to become a Fellow with the RSC. Selected by his peers on account of his outstanding contributions to science, Kubes is one of the most respected researchers in his field.

An answer to inflammatory disease and fatigue A research team from the Calvin, Phoebe and Joan Snyder Institute of Infection, Immunity and Inflammation (Snyder Institute) has identified how immune cells infiltrate into the brain during experimental liver inflammation, potentially explaining why people with inflammator y diseases develop symptoms such as fatigue. This new understanding could lead to treatments that improve the quality of life for patients with chronic inflammator y diseases.

Kubes has spent nearly two decades investigating the mechanisms leading to white cell recruitment in cardiovascular and immune disorders. He and his team identified that a gas produced inside the body, nitric oxide, functions to reduce white blood cell recruitment and maintain bodies in a non-inflamed state. Dr. Kubes, who co-leads the Alberta Sepsis Network with Faculty of Medicine colleague Dr. Chip Doig, is currently examining how white cells and bacteria battle in blood vessels and how we can help defeat these pathogens. The research is funded by the Alberta Heritage Foundation for Medical Research (now Alberta Innovates–Health Solutions).

“Sickness behaviors, such as fatigue and malaise, significantly impact the health related quality of life of individuals with these diseases. Our findings further our understanding of how patients with inflammator y disease may develop these symptoms and may generate potential new avenues for the treatment of these often incapacitating symptoms,” says Dr. Mark Swain, the study’s senior author and a member of the Snyder Institute.

“To date, clinical trials for sepsis drugs have been unsuccessful because, I believe, they are looking for a single drug for all septic patients. Think of cancer; we don’t use one drug for all kinds of cancer. We want to use a similar approach to sepsis,” explains Kubes.

Being elected to the RSC isn’t just an accolade to Kubes– it’s an opportunity to enhance some of the incredible research done in our country.

“The RSC plays quite an important advisory role in terms of policies as far as science is concerned in Canada. It’s something I feel pretty strongly about, to help Canada stay at the very cutting edge of research.”

Every year, the RSC selects about 60 people who are leaders in their fields to join the organization as Fellows.

Following nomination, current Fellows of the RSC peer-review the nominees based on their research and scholarly achievements. Those who are selected join a group of about 1,800 distinguished academics—each of whom has made an outstanding contribution to the arts, humanities or sciences in Canada.

Fatigue, lethargy and loss of interest in social activities are commonly encountered in patients suffering from inflammatory diseases such as hepatitis, arthritis, and inflammatory bowel disease (IBD).

The study published in the February 18th issue of The Journal of Neuroscience demonstrates the existence of a communication pathway between the inflamed liver and the brain.

Using a mouse model of inflammatory liver injury, Dr. Swain’s group found that white blood cells called monocytes infiltrated the brain, establishing a communication pathway between the inflamed liver and the brain. Moreover, in mice with inflamed livers blocking the recruitment of monocytes from the blood into the brain reduced sickness behaviours. These findings support previous research demonstrating the presence of immune cells in the brain following organ inflammation, challenging the long held belief that the blood-brain barrier prevents cells from accessing the brain.

The study was supported by the Canadian Institutes of Health Research, the Alberta Heritage Foundation for Medical Research (now Alberta Innovates–Health Solutions) and the Canadian Liver Foundation.

Paul Kubes, PhD, was elected to the Royal Society of Canada for his contributions to infection and inflammation research.

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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

The Alberta Children’s Hospital Research Institute for Child and Maternal Health (ACHRI)–a partnership between the University of Calgary, Alberta Health Services and the Alberta Children’s Hospital Foundation– is dedicated to the study and improvement of children’s and their mother’s and family’s health.

ACHRI’s vision of “healthy babies, healthy children and youth, healthy lives”, relates directly to our mission as an institute “to excel by international standards in the creation of knowledge and training of scientists and health professionals for the development of state-of-theart health care of mothers, children and communities”.

This statement matches ACHRI’s premise that optimizing a child’s developmental outcomes across the many transitions from conception to adulthood, leads to improved health over the entire individual lifespan, and prevents disease onset in adulthood. The Institute brings together basic scientists, academic clinicians, clinician scientists, health services and population health investigators from within various University of Calgary Faculties, and from Alberta Health Services and other agencies and research partners across Alberta.

ACHRI will translate discoveries made in the laboratory, the bedside and the community into better maternal, newborn, child and youth health for Albertans and others.

Researchers in ACHRI are organized into six theme groups: • Molecular and Genetic Basis of Development and Child Health • Reproductive, Maternal, Fetal and Newborn Health • Behavior and the Developing Brain • Childhood Cancer • Optimizing Health Outcomes • Healthy Living and Injury Prevention

ACHRI’s members have asked the Institute to focus on developing the following platforms: • Childhood cancer platform: – developing and assessing new drug therapies for children • Clinical, population health and health services research platform – improving child health care and health care services, systems and outcomes • Education and training platform – scholarly development of the next generation of scientists/clinician scientists • Translational genomics platform in a pan-Alberta context • Functional imaging and advanced microscopy platform complementing University and AHS resources • Additional institute wet and dry laboratory space

Bonnie Kaplan, PhD, and Deborah Dewey, PhD, are studying the role of pre-natal nutrition in the neurodevelopment of children.

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Study investigates link between pre-natal nutrition and neurodevelopment in children If you’re the type of person who truly believes ‘you are what you eat’, it might be safe to assume your belief in this philosophy would be strengthened if you were also an expectant mother. But do we really know what the best diet is for pregnant women?

When it comes to the brain development and function of children, or the maternal mental health of the mother after childbirth, the answer is no. But a multidisciplinar y study already under way in Alberta is seeking to answer these questions.

“We’re looking at what pregnant women are eating before and after their babies are born to determine how their nutrient intake and nutrient status might be influencing their child’s brain and behavioral development, as well as their own mental health,” explains Bonnie Kaplan, PhD, who is co-leading the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Funded by the Alberta Heritage Foundation for Medical Research (now Alberta Innovates–Health Solutions), the study is multidisciplinar y out of necessity.

“The information we collect isn’t just about nutrition.

We also collect things like DNA, blood, breast milk, and mental and physical health information, so our team is very diversified. We have nutrition researchers, family doctors, a perinatal specialist, psychologists, a psychiatrist, a thyroid specialist, a geneticist, and statisticians,” lists Kaplan, a professor in the Departments of Paediatrics and Community Health Sciences at the University of Calgary Faculty of Medicine.

The study falls in line with ACHRI’s strategic goal of combining basic biomedical science with clinical science. Deborah Dewey, PhD, who is co-leader of the APrON study and also a co-leader of ACHRI’s Behaviour and the Developing Brain Theme believes the collaboration that exists within the Institute can only benefit the study later on.

“We’d love to advance the APrON study beyond the five-year funding window that it has now, so having a connection to ACHRI means there may be researchers within the Institute that can perhaps come on board the study, or maybe use the data we are collecting for other research.”

10,000 Number of participants that researchers expect to recruit for the Alberta Pregnancy Outcomes and Nutrition (APrON) study, the largest pre-natal study in Canada.

Collaboration yields new discoveries When you ask senior clinical scientist Dr. David Johnson what the best par t of working at the Alber ta Children’s Hospital Research Institute (ACHRI) is, his answer is simple.

“It’s our relationship with the biomedical scientists.

The two areas can work hand-in-hand to ask the right questions and find the answers.”

It is this collaborative environment that brought clarity to Johnson’s study on a better treatment for bronchiolitis–a respiratory illness that hospitalizes more infants in their first year of life than any other single illness. With over 800 children and eight children’s hospitals participating, Johnson and his team discovered that the combination of epinephrine, better known to the general public as adrenaline, and a corticosteroid reduces the number of children with bronchiolitis who require hospitalization by a third, whereas neither drug used alone has significant benefit. The study was published in the New England Journal of Medicine.

“When we first got back the results of our study, we were mystified as to why use of the drugs together had such a profound effect whereas use of either drug alone seemed to have zero or at most a little effect.” Johnson explains. “When we started to dig into the scientific literature for an explanation, we were stunned to find two basic scientists at our doorstep here at the University of Calgary who are working on research that clarifies this. The potential to reduce an infant’s symptoms so dramatically that it substantially reduces hospitalizations is extremely encouraging, and so far no other treatment has been shown to do this.”

Dr. Mark Bieda, who works on the complimentary side as a junior medical scientist, agrees that the collaboration taking place at the ACHRI is very important.

Bieda’s focus of research is genome epigenetics, which studies the chemical reactions that switch parts of the genome on and off at strategic times and locations when an organism develops. As part of the ENCODE consortium, Bieda helped develop methods for analysis of large data sets focused on localization of proteins that bind to DNA and therefore control genomic activity.

Disruption of these systems plays a critical role in the majority of diseases. Earlier this year, the ENCODE consortium published a research paper on new insights into how DNA information comes to life in a cell. This paper was named one of the five most cited biology papers in 2009.

“This paper represents the first major results from the ENCODE consortium,” Bieda explains. “The project involved collaboration among many laboratories to produce a large volume of important genome information.”

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Libin Cardiovascular Institute of Alberta Dr. Todd Anderson, Interim Director C849 1403 29 Street NW, Calgary, Alberta, T2N 2T9 todd.anderson@albertahealthservices.ca www.libininstitute.org

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.

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.

The vision of the Libin Cardiovascular Institute of Alberta is to provide an efficient, integrated program of cardiovascular wellness, health care, research and education. The Institute’s strengths include: • Providing 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 modern 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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Predicting heart problems before they happen Researchers at the Libin Institute are at least one beat closer to discovering what role genetic information plays in the development of heart muscle disorders, thanks to the recently launched Cardiovascular Genetics Susceptibility Program.

According to team member Dr. Brenda Gerull−whom the Institute recruited in June 2009−the program’s main goals are simple: to study the molecular mechanisms of arrhythmias (irregular hear t beat) and hear t failure, as well as find out which factors predispose patients to developing these conditions.

“Many cardiac diseases have a family background which means inheritance plays a significant role in the cause of the disease,” explains Gerull. “I’m mainly focusing on molecular genetics of cardiomyopathies, which are heart muscle disorders with a strong genetic component. Most of them are inherited as an autosomal dominant trait, which means 50% of the offspring of affected parents will also be affected.”

In particular, Gerull is researching arrhythmogenic right ventricular cardiomyopathy (ARVC), an inherited disorder that sees myocardial tissue replaced by fibrous and fatty material, which can trigger an irregular heartbeat and an increased risk of sudden cardiac death.

So far, Gerull and her team have identified that a high percentage of patients with ARVC carry mutations that cause the disease, but have yet to discover what molecular mechanisms take place that lead towards arrhythmias and heart failure.

Once this process is better understood, Gerull is confident new diagnostic markers and therapies can be developed to prevent and treat those genetically determined diseases.

“My ultimate research goal will be to further understand the mechanisms involved in the development of cardiomyopathies, which may eventually lead to targeted gene therapies in the future,” explains Gerull.

“The greatest short-term hope is that we’ll be able to help ARVC patients and their families by offering genetic tests to diagnose the disease sooner, and by preventing sudden cardiac deaths with the implantation of internal defibrillators or pacemakers.”

Dr. Matthias Friedrich’s research proves the use of MRI as a superior way to detect damage caused by a heart attack as its happening.

Pioneering new methods to detect–and even prevent–heart attacks A study co-authored by Dr. Matthias Friedrich and Dr. John Tyberg, both of the Libin Cardiovascular Institute of Alberta, which proves the use of magnetic resonance imaging (MRI) as a superior way to detect damage caused by a heart attack as it’s happening, has been named the top research highlight in the field of cardiac MRI for 2009. The accolade, given by Dr. Anthony DeMaria, editor-in-chief of the Journal of the American College of Cardiology (JACC), is high praise from one of the most prestigious journals for clinical cardiology.

Friedrich and Tyberg, both members of the University of Calgary Faculty of Medicine, combined basic science research and clinical research to advance the use of MRI on heart attack patients. The technique is now common around the world because of its effectiveness.

“When a person has a heart attack and standard tests are inconclusive, instead of performing other tests we’ll have them undergo an MRI,” explains Friedrich.

“With this we can actually see the heart attack as it’s technically still happening.”

By intervening at a much earlier stage–which usually means transferring the patient to an angiography suite where doctors can determine the best course of treatment–doctors can limit the irreversible damage to the heart that can occur during a heart attack.

latest research also proves the accuracy of the MRI in very subtle heart attacks, or essentially before an actual heart attack has happened.”

The research, originally published in the April 22nd issue in the JACC, was the first trial of its kind. The new technique uses the distinct magnetic properties of water in the tissue to visualize the injury to the affected area in the heart, which at this stage is still reversible.

The method is completely noninvasive whereas other techniques require radiation or radioactive dyes. When combined with other available CMR protocols, a single CMR scan could also estimate the risk for heart attacks in the future.

45,790 Amount of new space, in square feet, the Libin Cardiovascular Institute of Alberta has for basic and translational science following its move into the Faculty of Medicine’s Health Research and Innovation Centre. The Institute’s new location is 33% larger than its old space.

“The use of MRI gives us information that we simply cannot detect with the use of CT angiography or any other imaging techniques,” Friedrich adds. “And our

2009-2010 Research Report | Page 13

The McCaig Institute for Bone and Joint Health Ms. Judy Crawford, Executive Assistant 3330 Hospital Dr. NW, Calgary, AB, T2N 4N1 jcrawfor@ucalgary.ca www.mccaiginstitute.com

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 osteoar thritis, rheumatoid ar thritis and related diseases. With the knowledge gained, the McCaig Institute strives to find treatments for these diseases to improve the quality of life for Alber tans, and to prevent the development of these conditions in future generations.

While primarily located in the University of Calgar y Faculty of Medicine, the McCaig Institute is comprised of researchers from five faculties who have come together to take multi- or trans-disciplinar y approaches to achieve the Institute’s goals. The consor tium of investigators includes basic scientists, or thopaedic surgeons, rheumatologists, kinesiologists, and biomedical engineers who bring diverse technologies and perspectives to bear on these complex chronic conditions. The primar y 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 Alber tans.

provincially which the McCaig Institute is developing in coordination with Alber ta Bone and Joint Health Institute. The McCaig Institute is also a focal point for interactions with other independent entities such as the Calgar y Bone & Joint Health Program of Alber ta Health Ser vices. The objective of these interactions is to implement the Institute’s successful research to patient populations effectively.

“The three independent components (McCaig Institute for Bone & Joint Health, The Calgar y Bone & Joint Health Program, and the Alber ta Bone and Joint Health Institute) and their associated par tners 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.

With new space in the Health Research and Innovation Centre, the McCaig Institute is focusing on recruiting new researchers to complement current activities and expand capacity.

The McCaig Institute interacts with the Alber ta Bone and Joint Health Institute in relation to health ser vices research. This relationship improves the connectivity

Neil Duncan, PhD, is using live tissue samples to innovate new treatments for disc related back pain.

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Targeting treatment for disc-related back pain

Joining forces to fight well-known joint disease

Disc-related lower back pain may sound like a hindrance, but the estimated 50,000 Canadians suffering from the condition likely have a different way of describing it: debilitating. Fortunately for those affected, the Spine Research Program at the McCaig Institute for Bone and Joint Health is here to help.

Relief could be in sight for an estimated four million Canadians suffering from osteoarthritis, thanks to researchers at the McCaig Institute for Bone and Joint Health, who are part of a five-year interdisciplinary team grant funded by the Alberta Heritage Foundation for Medical Research (now Alberta Innovates–Health Solutions).

“We are interested in pharmacological treatments and tissue engineering approaches to intervene less invasively in the earlier stages of disc degeneration,” says Neil Duncan, PhD, who leads the Spine Research Program along with McCaig Institute colleague Christopher Hunter, PhD. Low back pain can occur in various ways, but is often caused by a breakdown of the discs between the bony vertebral bodies of the spine. The spinal vertebrae provide the weight-bearing structural support; the intervertebral discs are the flexible elements in the spine that cushion the bones and allow mobility.

The team of researchers, which includes scientists from the University of Calgary and the University of Alberta, is developing new prevention measures, novel diagnostic strategies, innovative treatments, appropriate surgical interventions and medications to assist those suffering from osteoarthritis.

Duncan’s work is focused on understanding why communication between cells in the tissue that surrounds the gelatinous core of the disc breaks down over time. After a decade of research with animal models, Duncan is now studying the cells and tissue in diseased and injured discs from human patients, thanks to spinal surgeons Dr. Jacques Bouchard, Dr. Rick Hu, Dr. Paul Salo and Dr. Ganesh Swamy.

“In the animal tissues, we discovered the cells are connected through a network and not isolated as originally thought. We believe that in disc degeneration in humans, that network starts to break down and the cells can’t talk to each other, therefore they aren’t able to maintain or repair the tissue or respond to mechanical signals,” explains Duncan. For the last 18 months, he has studied parts of human discs that have been removed from patients who’ve undergone total disc replacement and scoliosis surgery. Beginning this year, Duncan will receive whole human spines to study as part of an organ donation program, providing him with healthy tissue to use as a control sample and to study a greater range of degenerative conditions.

Hunter’s research shares the same commitment to improving the lives of the people suffering with discrelated back pain, although in a different context. His laboratory is looking at developing biomaterials to patch tears that occur in the disc, treatment that could prevent total disc breakdown. With both Duncan and Hunter leading the way, the Spine Research Program at the McCaig Institute is making great strides towards fulfilling that commitment.

20 Number of live tissue samples studied by scientists at the McCaig Institute’s Spine Research Program in the last 18 months.

To do this, four distinct projects with 17 sub-projects are underway. A few examples of the work being carried out include the development of a series of new medications seeking to regenerate bone loss in affected joints; creating tools for doctors to determine the appropriateness of total joint replacements; and ways to reduce surgical wait times for those who are still in need of the procedure.

While it may be years before the new bone binding drugs that specifically target osteoarthritis are commercially available, a spin-off company, Oseometabolix Inc., was recently launched by team members at the U of A to build upon the research already funded by the grant.

According to Sue Hunter, project manager, the success of projects like these can largely be attributed to the multidisciplinary approach the team has devised in addressing and treating osteoarthritis. “All 36 principal investigators bring a different skill set and level of expertise to the team which allows them to share knowledge and make new discoveries which otherwise might not have been possible.”

The unique nature of this team grant has also accelerated young faculty members and trainees into scientific research, which she adds will pay huge dividends beyond the five-year scope of the funding. “The experience that trainees acquire while being a part of the osteoarthritis team is key in preparing them to lead the next scientific research generation.”

Dr. Cy Frank, co-team leader of the grant and a member of the McCaig Institute, believes this research and the work of the entire team will benefit the Institute for years to come.

“The Institute aspires to eventually become a worldleading centre in osteoarthritis research, education, care and prevention by building the capacity for osteoarthritis research in Alberta. It’s impossible to imagine reaching this goal without this program.”

The samples come from patients who’ve undergone total disc replacement surgery, and are analyzed to help improve and innovate new treatments for disk related back pain, which affects 50,000 Canadians.

2009-2010 Research Report | Page 15

Southern Alberta Cancer Research Institute Dr. Steve Robbins, Director 3280 Hospital Dr. NW, Calgary, AB, T2N 4Z6 www.sacri.ucalgary.ca

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 UCalgary 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.

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 Ser vices and UCalgar y Faculty of Medicine.

Building on community partnerships remains a key initiative at SACRI, something that is achieved through our Community Partners Advisor y 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 fought on many fronts and continues to achieve many victories. These include the introduction of preventive 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 continue to receive the best cancer treatments, but also that these Jennifer Cobb, PhD, is studying whether DNA damage is linked to cancer.

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Investigating whether DNA damage is linked to cancer

Renowned cancer researcher elected to Royal Society of Canada

Just about every time a cell dies another one is made to replace it. Imagine all the chances for error when millions of complex DNA repair and replication processes go on every day within our bodies. Under normal circumstances, our internal cell factories keep generating new and healthy cells.

A member of the Southern Alberta Cancer Research Institute and professor and head of the Department of Clinical Neurosciences at UCalgary, Dr. J. Gregory Cairncross may be best known for his research contributions to the field of neuro-oncology, the study of brain cancer. Well, at least that what he was best known for. Now he’ll also be known as a member of the Royal Society of Canada (RSC).

Unfortunately, these processes aren’t always perfect.

When cell production goes haywire, lost or misplaced DNA can result. This, in turn, can lead to chromosomal rearrangements and mutations–conditions often observed in cancer patients. But, are these observations truly a cause for concern?

Tackling these questions is Jennifer Cobb, PhD, assistant professor in the Departments of Biochemistry & Molecular Biology and Oncology at the University of Calgary, and member of the Southern Alberta Cancer Research Institute.

Cobb first became interested in the molecular mechanisms a cell uses to protect its genetic information when she worked as a post-doctoral fellow at the University of Geneva. Ten years later, Cobb’s investigations include DNA repair, DNA replication and chromosome segregation, all in hopes of understanding what actually initiates the process of transforming a healthy cell into a cancer cell.

While the medical community might agree that we can help prevent cancer by not getting too much sun, eating cer tain foods or being exposed to other known carcinogens, Cobb questions the “why” behind these findings. Her research explores what is going on at the molecular level inside the cell and how the genome is af fected when people are subjected to cancer-causing agents.

“We know that most cancers have genomic rearrangements and mutations. However, it is less clear whether these rearrangements and mutations cause cancer, are a consequence of cancer, or drive cancer growth,” explains Cobb. “We believe it is likely a combination of the three, and we hope our research will advance the understanding between mutations and tumour initiation.”

Cobb’s work could potentially lead to the identification of new chemotherapeutic targets in a patient’s fight against cancer.

This fall the RSC, Canada’s oldest and most prestigious academic body, elected Cairncross to become a Fellow with the RSC. Along with three other Faculty of Medicine members–Paul Kubes, PhD, Michael Walsh, PhD, and Samuel Weiss, PhD–he was selected by his peers on account of his outstanding contributions to science, and is one of the most respected scientists in his field.

“It’s always nice to be recognized for your work by your peers,” Cairncross says of his election to the RSC. “To be recognized by senior people in the academic community in Canada is an honour and very gratifying.”

In 1988, Cairncross and Dr. David Macdonald discovered that oligodendrogliomas, a type of brain cancer, are sensitive to chemotherapy. His work has provided a new framework for basic research and clinical trials in neurooncology. His current research interests include the detection of genetic signatures in gliomas using imaging and the personalized therapy for brain cancer guided by molecular analysis of tumour tissue.

Cairncross has published extensively on brain tumor biology and therapy, writings which have been cited over 6,000 times. He is a past recipient of the Farber Award for Brain Tumor Research of the American Association of Neurological Surgeons, the Research Award of Excellence of the American Association for Brain Tumor Research and the Merit Award of the European Association of Neuro-Oncology. In 2007, he was appointed director of the Clark H. Smith Brain Tumor Centre at the University of Calgary.

11% Number of Calgary cancer patients that participate in Southern Alberta Cancer Research Institute clinical trials, well above the North American average of 3-5%. More than 1 in 10 cancer patients benefit from the advanced research through these clinical trials conducted in Calgary.

Dr. J. Gregory Cairncross, in his lab at the Faculty of Medicine.

2009-2010 Research Report | Page 17

Calgary Institute for Population and Public Health Dr. Bill Ghali, Director 3280 Hospital Drive NW, Calgary, AB, T2N 4Z6 www.ucalgary.ca/cipph wghali@ucalgary.ca

Removing inequities in population health and improving health care deliver y requires trans-disciplinar y approaches to understanding the links between health determinants and health outcomes. Through evidenceinformed inter ventions we can create positive new trends in health that impact Canadians and others around the world in a visible and meaningful way.

The Calgar y Institute for Population and Public Health (CIPPH) brings together over 160 of Alber ta’s researchers and health professionals–drawn from multiple university faculties and schools, health ser vice 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 trans-disciplinar y 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 par tnerships among individuals, teams and organizations, giving voice to their collective vision and intent.

Susan Cork, PhD, is assessing the risks of disease transmission between humans and wildlife.

Page 18 | 2009-2010 Research Report

Turning research into positive health results

Helping our researchers heal our communities

It’s not something most people would consider a normal way to assess health risks to human populations; studying a group of elephants in India who suffer from a strain of human tuberculosis, the same as their human keepers. But this type of cross cutting research–a multidisciplinar y mix of ecology, veterinar y and medical science–is typical for Susan Cork, PhD, a member of the Institute for Population and Public Health (CIPPH), and the Faculty of Veterinar y Medicine at the University of Calgar y.

Dr. William (Bill) Ghali cares about the health of our communities. He shows this every day through his work as an internal medicine specialist, but just as important in ensuring our continued health is his research into health systems; what works, what can be improved, and what level of healthcare patients are receiving.

Working with David Abraham, a UCalgary postgraduate student, Cork and a multidisciplinary team of researchers are assessing the risks of disease transmission between humans and wildlife, both captive and free-ranging. Cork and her co-workers are trying to find out how disease is transmitted between humans and animals, with the aim of developing suitable interventions to minimize the spread of the disease.

“I’m hoping the data collected by our research team can be used to help assess the health risks to and from humans, as well as other wild and domestic animals. This will help us provide disease control recommendations to help the authorities develop and apply effective risk mitigation measures to minimize the risk of disease transmission,” says Cork, head of the Department of Ecosystem and Public Health in the Faculty of Veterinar y Medicine.

She is also applying her background in disease ecology, risk assessment and public policy towards another research project, this in western and northern Canada.

Along with a variety of multidisciplinar y researchers at UCalgar y and the provincial government, Cork will be investigating whether or not caribou in various habitats across northwest Canada have been exposed to West Nile virus. This work and concurrent studies testing for the presence of the virus in mosquitoes may help predict disease risk to animal and human populations in the region.

163 Number of members the Calgar y Institute for Population and Public Health has recruited in its first year.

These members are leaders in a broad spectrum of researchers and health professionals, drawn from multiple university faculties and schools, health ser vice providers, government agencies and community organizations.

With this multi-level commitment to health, it’s no wonder why Ghali has been chosen as the first director of the Calgary Institute for Population and Public Health (CIPPH), a position he will take up July 1, 2010.

The Institute was launched in April 2009 and has over 160 members, from a wide range of disciplines including medicine, nursing, social work and social sciences. The researchers all have one common goal: to improve health services and affect public policy.

“Our Institute is a large tent of people, we have all the ingredients here for Calgary to be a leader in public health on the national scene and international stage,” says Ghali.

In his new role, Ghali will help link together members in the Institute who have similar research interests and foster team initiatives. He also plans to take the Institute’s research and align it with provincial par tners and decision makers as the research has direct applications.

“This area of research has really grown at the University of Calgary over the last number of years, and there are so many great things happening here,” he says. “Our work has impact and it’s important to use it so tangible actions can be made.”

In addition to being a clinician, Ghali is still very involved with his own research. In November 2009 he co-authored a study published in The Lancet concluding that physician wellness is a key factor when operating a quality healthcare system. In February 2010, he was the senior author on a study that looked at Canadian cities and their access to optimal life saving heart treatment.

Ghali was also instrumental in the Medical Ward of the 21st Century research project in collaboration with Alberta Health Services.

Dr. Ghali is a professor in the Depar tments of Medicine and Community Health Sciences and holds a Canada Research Chair in Health Ser vices Research and is an Alber ta Heritage Foundation for Medical Research Senior Health Scholar (now Alber ta Innovates–Health Solutions).

2009-2010 Research Report | Page 19

Centre for Advanced Technologies

AT

CENTRE FOR ADVANCED TECHNOLOGIES

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 • Micro-CT/3D Morphometrics Laboratory • Health Sciences Animal Resources Centre (HSARC) • University Core DNA Services (UCDNA Services) • Southern Alberta Mass Spectrometry Facility • Southern Alberta Microarray 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 has recently began operations, providing 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, business manager for CAT.

140 Number of principal investigators and researchers within the Faculty of Medicine who use the Flow Cytometry Lab and the Microscopy and Imaging Facility to further their research.

Page 20 | 2009-2010 Research Report

Dr. John Reynolds, Director 5E23, TRW Building 3280 Hospital Drive NW, Calgary, AB, T2N 4Z6 cat.ucalgary.ca macklon@ucalgary.ca Three dimensional imaging facility a powerful resource for researchers 3D movies may be popping up at your cinema with regularity these days, but movie goers aren’t the only ones enjoying the benefits of three dimensional technology. Scientists at the Centre for Advanced Technologies at the Faculty of Medicine are reconstructing cells, subcellular structures and particles in 3D at unprecedented resolution.

“If you want to understand something it’s much better to hold it in your hand and rotate it,” explains Tobias Fürstenhaupt, PhD, an electron tomographer in the Microscopy and Imaging Facility. “You get a much clearer image of what’s inside.”

Typically cells and particles are analyzed in electron microscopes by scientists in 2D. But as Fürstenhaupt explains, this can be misleading as with each single micrograph a myriad of nanoscaled structures, macromolecules and membranes are all seen on top of each other. This often makes it impossible to understand what is going on. In contrast, electron tomography reveals the microscopic world in 3D. But creating the 3D image is a difficult task. Gathering the raw data and photographing a cell section from every angle using the microscope takes around two hours, and to perfectly reconstruct the 3D image usually takes another six to eight hours. “While there are computer programs to help with reconstruction, the technique heavily relies on human expertise to manually piece it together,” explains Fürstenhaupt. Another difficulty is the training of tomographers. The job is extremely demanding and can only be taught by performing the same reconstructive task over and over.

“Tobias is ‘a rare species’,” says Matthias Amrein, PhD, director of the Microscopy and Imaging Facility. “He knows what is important and how to get good data. I’m proud we could attract such a high caliber expert in this increasingly important field.”

Even with these hurdles, the facility is gaining a valuable reputation within Canada as a leader with the ability to provide expertise in the world of electron tomography.

While the facility is still relatively small it collaborates with over 80 labs at UCalgary, and 20 researchers outside the University have used its resources last year. Researchers are already starting to adopt this powerful methodology for their studies in diabetes, lung cancer, nanoparticle toxicity and many applications of immunology.

Dr. John Reynolds with colleague Laurie Robertson in the flow cytometry lab.

Advancing research through technology “This facility is used by researchers from all over the Faculty of Medicine. They represent some of the most internationally renowned scientists we have and without this facility their research suffers.”

Dr. John Reynolds isn’t exaggerating when he speaks of the flow cytometry lab, a resource that’s part of the Centre for Advanced Technologies (CAT). With a new, upgraded cell sorter and cell analyzer, the lab is a crucial tool for researchers, particularly those in the fields of immunology, infection and cancer research.

Flow cytometry is a sophisticated technique of single cell analysis. It simultaneously measures and analyzes multiple physical and molecular characteristics of single particles, usually cells, as they flow in a fluid stream through a beam of light. Some of the characteristics measured include a particle’s relative size, granularity, surface and internal complexity and relative fluorescence intensity.

“This new cell sorting machine is one of the most advanced in the world. It will do four-way sorting instead of two like our last machine, it uses three lasers compared to one, the upgrades are numerous,” explains Reynolds.

Right now 60 principal investigators at the Faculty of Medicine rely on the services of the flow cytometry lab, as well as researchers from other University of Calgary faculties and the University of Lethbridge.

Even outside agencies such as Agriculture Canada, Alberta Fish & Wildlife, Canada Biosciences, and various pharmaceutical companies are clients. Not only do the researchers who use the facility benefit from the new equipment, they’re also provided the services of Laurie Robertson and Laurie Kennedy, who have over 50 years of combined experience in cell sorting and analyzing.

With a total cost of around $600,000 for the two machines, the Centre for Advanced Technologies had to pool resources from other departments and institutes to purchase the equipment. “Because this facility is so critical for the faculty, we put out a call for funds to the people who use it,” says Reynolds. “The response was tremendous and we received funds from several sources, many of them using contingency or emergency funding they had set aside.”

With the advancement of research the facility provides, it sounds like money well spent.

2009-2010 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

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

The Centre is founded upon the Faculty of Medicine’s philosophy of flowing research discoveries from the laborator y 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 laborator y, and, finally, developing new medical solutions for patients.

In 2009, activity has been focussed on moving in to the new environment and further streamlining clinical health research activities. The Heritage Medical Research Clinic (HMRC) is now located in the Teaching, Research and Wellness building (see stor y opposite page). It features space for clinical assessment of patients, patient beds and treatment chairs for intravenous infusions of study medications; an inhouse research pharmacy (a sub-site of the Foothills

Medical Centre pharmacy); and laborator y facilities for preparing specimens for shipping. The space is being used for both industr y-sponsored research as well as publically funded projects. Additionally there is office space for clinical research nursing staff and support staff. Activity at the centre is growing and we hope to have it operating at full capacity in the near future.

Additionally, strides have been made in many areas of clinical research to streamline communication among peers to clearly identify concerns and issues. The integration of research administrative functions such as legal ser vices and contracts management, accounting ser vices and regulator y/ethics review ser vices is an ongoing project of the University. This will ultimately impact clinical health research in a positive way as processes become more streamlined and efficient. This will tie in with the provincial approach to clinical health research which is being developed.

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 Ser vices’ infrastructure, programs and ser vices, and will continue to play a vital role in the ongoing success of those involved in clinical research.

Carolyn Robertson, RN, speaks to a patient at the Heritage Medical Research Clinic, part of the Calgary Centre for Clinical Research.

Page 22 | 2009-2010 Research Report

New facility boosts clinical trial capacity When a company moves into a new, larger building or space, usually the benefits are immediate and obvious.

More times than not, employee morale is improved as is the quality of work. But rarely when a company moves into a new facility does the health of those in the community and beyond increase as well, even perhaps improving the lives of millions of people.

Welcome to the new home of the Heritage Medical Research Clinic (HMRC), par t of the Calgar y Centre for Clinical Research at the Faculty of Medicine.

Located on the fifth floor of the Teaching, Research and Wellness building at the Foothills Medical Centre site, the HMRC now boasts nearly 10,000 square feet of space–double the size of their previous area in the Heritage Medical Research Building. “We went from a fairly small clinical area to ver y large area, and it’s a huge improvement not only for our staff and our researchers, but also for all of our patients who are par ticipants in the clinical trials,” explains Carolyn Rober tson, RN, the clinic manager.

The new facility also features 12 exam rooms, a substantial increase from the five exam rooms they had before, and a much larger and improved phlebotomy area (collection of blood samples). With the extra space also comes more oppor tunity. The HMRC is now able to include more intravenous studies, par t of the 110 clinical trials currently being conducted from different specialty areas such as cardiology, movement disorders, epilepsy, hyper tension, hepatitis, gastrointestinal and respirator y studies. There is also room in the building for fur ther expansion.

“We tried to create a comfor table place for our patients, staff and researchers,” explains Rober tson.

“It’s impor tant for ever yone to enjoy the atmosphere we have here. With clinical trials, sometimes the patients will be coming back to our location for five to 10 years and we need to ensure that they look for ward to their visits, feel welcome and enjoy the experience.”

By providing a facility where Calgar y investigators and their colleagues from around the world can work and collaborate, the HMRC allows clinicians and scientists to work directly with patients to eventually develop new medical solutions for various diseases and health issues.

110

Technology improving the clinical trial process Imagine yourself as a scientist whose spent years conducting research that could help doctors care for suf fering patients. Your research has shown promising signs throughout the initial testing stages, and now you’re ready to test it in clinical trials. If you were this researcher, setting up such a clinical trial would seem to be the easy par t of your already long journey. Unfor tunately this sometimes isn’t the case, but thanks to the Calgar y Centre for Clinical Research (CCCR) and the Faculty of Medicine’s Health Innovation and Information Technology Centre (HiiTeC), that’s likely to change.

“There is quite a challenge for researchers to actually line up a clinical trial with human patients,” confers Tom Durnin, business transformation manager at HiiTeC. “To get a proposed clinical trial off the ground there is a complex process that it must go through, including several stages of approvals and reviews. And at any number of those stages there could be a number of issues or follow up activities required.”

In an effor t to streamline and make this process more efficient, Dr. Michael D. Hill, director of the CCCR approached the HiiTeC team with an idea for a paperless, computerized process that would be easier not only on the researchers, but also on the business administrators who have to deal with all the information that comes with a proposed clinical trial. He hoped it would also help ensure all stages and approvals of proposed clinical trials were met and documented properly.

“After meeting with Dr. Hill, we devised a new system where instead of filling out a paper form to begin the process of getting a proposed clinical trial star ted, a researcher can now do it all from his or her computer, and they can monitor their proposal as it moves through each stage of the system,” explains Durnin.

These stages include research accounting, legal ser vices, and depar tmental approvals. With the ability to submit their proposed clinical trial from the research intranet site that all Faculty of Medicine members have access to, scientists are free to focus on their actual research and will receive approval for a clinical trial faster.

“The system is now in the user testing phase, and is getting a great response. The next step is to fine tune it before it’s fully launched,” says Durnin. That’s expected to happen sometime this summer.

Number of clinical trials currently being conducted at the Heritage Medical Research Clinic at the Calgary Centre for Clinical Research, one of the largest and most diverse clinical research centres in Canada. These trials come from a broad spectrum of medical specialties such as cardiology, movement disorders, epilepsy, hypertension, hepatitis, gastrointestinal and respiratory studies.

2009-2010 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

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, 475 graduate students–17.4% of them international–in the masters (MSc, MBT) and doctoral (PhD) programs carry 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 institutes: • • • • • • • •

Biochemistry & Molecular Biology Biomedical Technology (MBT) Cardiovascular & Respiratory Sciences Community Health Sciences Gastrointestinal Sciences Immunology Microbiology & Infectious Diseases Medical Science, with specializations in: - Biomedical Engineering - Cancer Biology - Critical Care Medicine - Joint Injury & Arthritis - Medical Education - Molecular & Medical Genetics - Mountain Medicine & High Altitude Physiology • Neuroscience

careers, and for careers in the design, management and implementation of health care delivery programs.

The combined MBT/MBA program graduates students who are fully versed in all aspects of biotechnology from the lab bench to the board room, and who will contribute to the growing biotech business and economy in Alberta and beyond.

Close to 40% of our graduate students are suppor ted through competitive awards from external agencies including the Alber ta Heritage Foundation for Medical Research (now Alber ta Innovates–Health Solutions) the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC), the Alber ta Cancer Board (ACB) and the Hear t & Stroke Foundation. This has brought in over $2.9 million to the Faculty of Medicine in suppor t of research. Students also receive competitive stipends from super visors’ operating grants, Faculty of Graduate Studies Graduate Scholarships and graduate teaching assistantships.

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 2009, our graduate programs convocated 98 students.

“Graduate education depends critically on the personal mentoring of the student by a faculty member, which ensures a high quality education.

The one-on-one instruction is supplemented by over 120 intensive graduate courses in the Faculty of Medicine,” says Frans van der Hoorn, associate dean, Graduate Science Education.

In addition, more than 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 Page 24 | 2009-2010 Research Report

Masters student Ame-Lia Tamburrini, whose thesis earned her a Governor General’s Gold Medal.

Finding “nothing” earns student Governor General’s Gold Medal What kind of thesis does it take to win a Governor General’s Gold Medal? The award, given to the masters student who has achieved an outstanding academic record combined with an exceptional thesis, represents one of the highest honours a masters student can achieve at the University of Calgary. So what kind of discovery did Ame-Lia Tamburrini, a student in the MSc. Epidemiology degree program and the winner of the 2009 Governor General’s Gold Medal, uncover with her research?

“Actually, I found nothing!” Finding ‘nothing’ is really just Tamburrini being modest. Her thesis, which looked into the association between serum cholesterol (cholesterol that is found in the bloodstream) and dietary cholesterol and how they relate to mammographic density, is a detailed and nuanced analysis of important breast cancer data. Mammographic density is a risk factor for breast cancer in post-menopausal women, but it is still unknown how dense tissue–which is believed to be made up of stromal and epithelial tissue–is formed in the body.

“Using data collected from the Alberta Physical Activity and Breast Cancer Prevention Trial conducted by my supervisor Dr. Christine Friedenreich, my research focused on cholesterol because it is a precursor to estrogen formation, and estrogen is a well-known breast cancer mechanism,” explains Tamburrini.

After thorough analysis, Tamburrini found no relationship between these two types of cholesterol and mammographic density. While she may have technically found ‘nothing’, her results do provide some important information.

“I still learned a lot from having a null study, because you still have to say ‘what do these results mean in relation to previous studies’,” says Tamburrini. “Other studies in this area of research have found mixed results but my study found nothing. So in the end I concluded that maybe we need to be looking elsewhere at other mechanisms along this pathway. Cholesterol and mammographic density may not be the most key relationship to be looking at.”

185 Number of postdoctoral trainees at the Faculty of Medicine–with 35% coming from outside Canada–who are a pivotal part of the Faculty’s research enterprise. Many of these trainees are recipients of external, competitive fellowships and bring over $3.9 million into the Faculty of Medicine in support of research.

Fighting disease in the clinic and the laboratory Braedon McDonald is an overachiever. He’s extremely hard working, focused and talented–and he’s also the recipient of the prestigious Dr. Lionel E. McLeod Research Scholarship. Established in memory of Dr. McLeod, the founding president of the Alberta Heritage Foundation for Medical Research (now known as Alberta Innovates– Health Solutions), this award assists academically superior students to undertake full-time research training in a discipline relevant to health research.

But he’s also a glutton for punishment. At least you’d assume he was, being part of the Leaders in Medicine MD/ PhD program at the University of Calgary. The program allows students to complete both their doctor of medicine (MD) degree and their doctoral (PhD) degree at the same time. Where many would struggle to complete just one of those programs on their own, Leaders in Medicine students complete both–even if it takes a little bit longer.

“I’ve already completed my first two years of medical school, and I’ve just completed my first year of PhD studies,” explains McDonald.

McDonald works in the laboratory of Paul Kubes, PhD. His research focuses on how to block the immune system and notably the white cells from reaching the liver and injuring it. Sepsis or infection that affects the whole body (meningitis, appendicitis, severe H1N1, etc.) kills more Albertans than any other disease. But it’s not the microbes that kill, it’s the immune system which releases its most potent and toxic molecules in an attempt to kill the bacteria. Innocent bystanders, namely the lungs, liver, heart, brain and other tissues, are often injured.

McDonald’s research has identified a molecule, CD44, which appears to function as glue allowing the white cells to accumulate in the blood vessels of the liver.

By stopping the white cells from reaching the liver they prevent this inappropriate inflammation.

For McDonald, completing both degrees at the same time was a great decision.

“I came to the University of Calgary to work with Dr. Kubes, but the school offers a lot of other added benefits, one of them being their three-year doctor of medicine program instead of the usual four-year program.”

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

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

2009-2010 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. In 2009, some 125 endowments resided at the Faculty of Medicine. Typically, an endowed Chair has a value equal to or superior to $3M while Professorships have a value equal to, or superior to $1.5M. 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. Ten years ago we had one endowed Research Chair and Professorship, today we have 53.

Alberta Cancer Foundation Chair in Brain Tumor Research Dr. Gregory Cairncross Alberta Cancer Foundation Chair in Biostatistics In Search Alberta Children’s Hospital Foundation Barb Ibbotson Chair in Pediatric Hematology In Search Alberta Children’s Hospital Foundation Chair in Pediatric Genetics In Search Alberta Children’s Hospital Foundation Chair in Pediatric Immunology In Search

Arthritis Society Chair in Rheumatic Disease/ Rheumatology Dr. Marvin Fritzler Arthur J.E. Child Chair in Rheumatology Research In Search AstraZeneca Chair in Cardiovascular Health Promotion and Disease Prevention In Search Brenda Strafford Foundation Chair in Alzheimer Research Dr. Minh Dang Nguyen Brenda Strafford Foundation Chair in Geriatric Medicine Dr. David Hogan

Alberta Children’s Hospital Foundation Chair in Pediatric Research Dr. Brent Scott

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

Alberta Children’s Hospital Foundation Cuthbertson and Fischer Chair in Pediatric Mental Health In Search

Calgary Foundation - Grace Glaum Professorship in Arthritis Research Dr. David Hart

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 In Search 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

Campbell McLaurin Chair for Hearing Deficiencies Dr. Jos Eggermont Chair in Hepatology In Search Chair in Pediatric Asthma In Search Crohn’s & Colitis Foundation of Canada Chair in Inflammatory Bowel Disease Research Dr. Keith Sharkey

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

Enbridge Research Chair in Psychosocial Oncology Dr. Linda Carlson

Julia McFarlane Chair in Diabetes Research Dr. Pere Santamaria

Engineered Air Chair in Cancer Research Dr. Susan Lees-Miller

Kids Cancer Care Foundation Chair in Pediatric Oncology In Search

Dr. Frank Leblanc Chair in Spinal Cord Research Dr. Peter Stys

Kinsmen Chair in Pediatric Neurosciences In Search

Page 26 | 2009-2010 Research Report

Lance Armstrong Research Chair in Molecular Cancer Epidemiology In Search 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 In Search Novartis Chair in Schizophrenia Research Dr. Jean Addington N.B. Hershfield Professorship in Therapeutic Endoscopy In Search 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 Roy and Vi Baay Chair in Kidney Research New! In Search Dr. Lloyd Sutherland Professorship in IBD/GI Research In Search Svare Professorship in Health Economics Dr. Herbert Emery Westaim – ASRA Chair in Bacterial Biofilm Research Dr. Shawn Lewenza

Financial Statements 2008-09 REVENUE FOR BIOMEDICAL AND HEALTH CARE RESEARCH BY SOURCE OF FUNDS Federal Government Sources Hospital/University Internal Sources Local Sources National Foundations Other Foreign Sources Private, For-Profit Canada Provincial Foundations Provincial Government Sources USA Sources National Not-For-Profit Sources Multiple Sources Provincial Not-For-Profit Sources Total Revenue for Biomedical and Health Care Research:

PROVINCIAL GOVERNMENT SOURCES

(includes departments and affiliated agencies)

Adult Research Committee of the Calgary Health Region Alberta Advanced Education and Technology AHFMR Alberta Cancer Board Alberta Genomic Instability & Aging Conference Alberta Health Services Alberta Infrastructure Alberta Innovation and Science Arthritis Society CHR in Rheumatic Diseases ASRIP & CFI ASRIP & WED Cross Cancer Institute icore Induced Sputum Analysis Infection Control/CHR Search Canada VP Research Calgary Health Region Workers’ Compensation Board–Alberta Provincial Government Sources Total:

FEDERAL GOVERNMENT SOURCES

$35,849,314.86 $3,556,225.22 $10,846,908.56 $6,751,233.03 $9,569,847.50 $905,224.72 $6,868,983.75 $2,713,584.13 $36,913,751.96 $10,504,007.25 $1,399,822.33 $1,909,432.33 $1,287,189.79 $129,075,525.43

$25,000.00 $38,581.50 $20,486,193.21 $24,475.00 $770.00 $10,220,122.44 $55,928.56 $737,983.45 $201,847.82 $405,892.84 $3,649,882.91 $62,233.32 $250,414.00 $4,761.33 $48,000.00 $492,189.52 $50,000.00 $159.476.06 $36,913,751.96

(includes departments, crown corporations and agencies)

Canada Foundation for Innovation Canada Research Chair Award Canadian HIV Trials Network Canadian Stroke Consortium/Canadian Stroke Network Canadian Cochrane Centre CIHR Environment Canada First Nations and Inuit Health Branch International Development Research Centre Natural Sciences & Engineering Research Council of Canada Networks of Centres of Excellence Public Health Agency of Canada Social Sciences and Humanities Research Council of Canada Federal Government Sources Total:

$1,224,198.69 $4,875,000.20 $62,902.57 $5,000.00 $1,000.00 $27,536,806.37 $31,673.60 $160,000.00 $54,051.00 $1,044,989.00 $584,799.43 $217,244.00 $51,650.00 $35,209,281.21

2009-2010 Research Report | Page 27