UCalgary Medicine is published by the University of Calgary Cumming School of Medicine, providing news and information for and about our faculty, staff, alumni, students, friends and community. Editorial Team Jordanna Heller, Director, Communications and Media Relations Marta Cyperling, Manager, Media Relations Amy Dowd, Manager, Internal Relations Amanda Fisher, Communications Coordinator Aisling Gamble, Communications Advisor, Events and Recognition Copy Editor Alex Frazer-Harrison Dean Jon Meddings Vice Dean Glenda MacQueen Senior Associate Deans Ronald Bridges, Faculty Affairs Jocelyn Lockyer, Education Marcello Tonelli, Health Research Gerald Zamponi, Research Associate Deans Tara Beattie, Graduate Science Education Sylvain Coderre, Undergraduate Medical Education Lara Cooke, Continuing Medical Education and Professional Development Janet de Groot, Equity and Professionalism Derek Exner, Clinical Trials Jennifer Hatfield, Strategic Partnerships and Community Engagement Ebba Kurz, Undergraduate Health and Science Education Doug Myhre, Distributed Learning and Rural Initiatives David Keegan, Faculty Development Paul Schnetkamp, Research Infrastructure Maureen Topps, Postgraduate Medical Education Ray Turner, Research Grants Samuel Wiebe, Clinical Research Graphic Design Amanda Fisher Photography and Illustrations Riley Brandt, Amanda Fisher, Scott Forsyth, Julie McLaughlin, Bruce Perrault, Kim Smith, Candice Ward, Kristen Wilson
On the cover: The Precision Medicine Edition Managing Editor Kathryn Kazoleas T 403.220.5012 E kjslonio@ucalgary.ca
Ancestral guide, Scott Forsyth
Precision medicine includes tailored therapies targeted to specific individuals, afflicted with distinct versions of a disease. The objective in precision medicine is to “crack the code” and stop a disease in its tracks; stop it before it even starts. As science evolves, we can use the threads of emerging technologies, collaborative research and clinical observations to sew together a new way of thinking, a new way of conducting clinical trials, a new way of diagnosing, a new way of treating and, one day, a new way of preventing disease. At the Cumming School of Medicine, we are strategically investing in resources – people and research platforms in genomics (genetic sequencing), imaging (seeing what has previously been unseeable), clinical informatics (analyzing large sets of biological data) and the microbiome (the bacteria that outnumber our own cells) – and we’re investing in partnerships with other institutions, including the University of Alberta, to build a strong provincial vision for precision medicine. or the past 30 plus years, medicine has been doing a decent job of diagnosing and treating the average illness in the average human being. But who is really average? What diseases can we consider average? As we are finding out, the combination of variants in genes, environment, lifestyle and disease biology means there’s really no such thing as “average” when it comes to medicine. What we call breast cancer isn’t one disease, it’s many different types of diseases. Foreign bacteria outnumber our own cells 10 to one in our bodies, and they vary between people. There are infinite possible genetic combinations that make a person anything but “average”. As a medical school we seek innovative answers to difficult health-care questions. We strive to create the future of health. And the future of health is something called precision medicine.
And we’re really just getting started. What an exciting time not to be average. This themed edition of UCalgary Medicine magazine showcases just some of the precision medicine initiatives currently underway, and under development, at the Cumming School. Spring 2016 also marks the beginning of our 50th anniversary celebration at the University of Calgary; an appropriate milestone for our journey in this evolution of medicine. Here’s to 50 years of innovation, ambition and community connections, and to a future of even better health and health care. Jon Meddings, MD Dean, Cumming School of Medicine University of Calgary
4
edical students know Lynne Cousineau well. After all, she spends several hours a week in the clinics with them. She’s not always known as Lynne, though, nor is she the same age, nor is she in the clinic for the same reason. This might seem a bit strange, but in medical education it’s anything but. Lynne is one of approximately 200 standardized patients at the University of Calgary’s Cumming School of Medicine (CSM) – actors hired to portray patients as part of medical school education.
Standardized Patients, or SPs, were introduced into the medical school curriculum in 1994-95. The University of Calgary was one of the first medical schools in North America to introduce the program with many others following suit shortly thereafter. The program is a safe and supportive environment
for medical students to learn in, where they have the opportunity to learn and practice their assessment, treatment and communication skills. “Before, every medical student would see different patients on the wards,” says Medical Skills Coordinator Rainer Kahl, an actor and former SP himself. “But this type of program allows us to actually have all medical students see the same patients, with the same syndromes. This really equalizes the assessment pool.” Patient “stories” are developed by course instructors, based on the needs of the curriculum, for assessment purposes or for remediation. They also vary in scope based on where a student is in his/her medical training. Scenarios range from basic physical-exam components such as taking blood pressure, to discussing birth control with teens, to providing palliative care or approaching family members to discuss organ donation. Cousineau has been an SP at the CSM for about seven years. A trained actor, she’s been involved with theatre and television and worked as an SP in Edmonton prior to
moving to Calgary. She’s worked as an SP in a variety of scenarios where students are learning the basics of physical exams, such as taking a blood pressure or conducting an eye exam, and in more involved scenarios where she’s tasked with not only portraying various illnesses such as a stomach ache or acid reflux, but as being a patient with a specific personality and/or temperament. “I’ve been around so long, sometimes I can point [the students] in the right direction during physical exams, if they’re stuck,” Cousineau says. “If they’re having difficulties finding the JVP (jugular venous pulse: a pulse originating in a vein on the right side of the neck), for example, I can just say, ‘Just look over here.’ Sometimes, the preceptors will even just say, ‘Just ask Lynne if you need help.’” She adds that in scenarios focused more on the communication aspect of clinical experiences, she isn’t able to say anything out of character. Knowing where the JVP is isn’t all that Cousineau has picked up during her years as an SP. A friend of hers who is diabetic
had low blood sugar while out one night. She was deteriorating quickly, to the point where she was nearing a comatose state. Knowing the clinical signs of low blood sugar from her experience as an SP, Cousineau knew what to do and that time was of the essence. Her actions, according to EMS when they arrived, saved her friend’s life.
Courtney Charnock, an SP since August 2015, recalls one case she was involved in where she was required to portray a pregnant woman who had been injured while walking her dog. “I had to have my makeup done and wear a full costume,” she says. “I even had to wear a pregnant belly. They are really committed to making this all believable.” A trained actor who recently graduated from the university herself, Charnock says despite the commitment to believability, on occasion it does happen when there isn’t enough buy-in from the students. That poses a particular challenge for her to convince them to act as though the scenario is real.
The Medical Skills rooms, where students assess SPs, are set up to look like a standard doctor’s office albeit equipped with a microphone and one-way mirror that leads to another, similar looking room. While a medical student is in a clinic room examining an SP, their preceptor and the rest of their class is on the other side of the glass, listening, observing and making notes. After the scenario concludes, SPs join the students and preceptors to give their feedback from the perspective of the patient they just portrayed. “We’re asked to give the students feedback on things such as, how we felt as a patient, when they said certain things or did certain things,” Cousineau says. “There is a feedback protocol we’re all trained in. For instance, if we see an area that might require a bit of improvement, it’s best to begin the conversation with a positive critique. For the most part, the students are very receptive and appreciative of what we have to say.” The Medical Skills staff stops at nothing to ensure scenarios are as realistic as possible. SPs are taught various responses to physical exams, both when conducted correctly and incorrectly, are coached on mood (i.e. if they’re going to be an agreeable patient, or challenging patient), are briefed on medical histories of the patient they’re portraying and are even tasked with wearing costumes, makeup and using props when necessary.
“The professors are very aware of this and really push us as SPs to make it as believe as possible for the students,” Charnock says. “In one of my cases, the students came in, in pairs and were smiling and noticeably having a hard time with it. I just stayed in character and politely said, ’Oh I’m sorry it makes me really uncomfortable when you’re smiling’ and they got back into a professional manner very quickly.” With each day as an SP bringing with it new cases, new students and new challenges, both Charnock and Cousineau agree it’s nothing short of a gratifying experience. “Sometimes we’ll do a case with a student, go into feedback, and the preceptor will want to try the scenario again, or alter it slightly with the same student,” says Charnock. “It’s really rewarding to see the students take advice or to build on personable qualities we mentioned were beneficial, and to carry that into the second round.” Adds Cousineau: “I have such admiration for these students. Some of them are married and have families and busy lives outside of school. Just watching them go through all of this learning and knowing how much knowledge they have to acquire in addition to their regular, day-to-day lives…I learn a lot from them as well. It is a very rewarding experience.”
The CSM hosted the first trauma day in summer 2015. University medical, nursing and social work students, along with MRU nursing students and allied health professionals from SAIT (including EMS and respiratory therapy) all took part in a simulated crash scene. Standardized Patients acted as crash victims and their families. Standardized Patients donned a number of costumes and makeup to make the scene believable – complete with fake blood and shards of glass protruding from wounds.
Standardized Patients at the Cumming School of Medicine range in age from approximately two years old to 80 years old.
Various electronic patient simulators are also used to train medical students. These simulators can be manipulated by the preceptors to change physiological responses such as blood pressure and respiratory rate in response to decisions students make.
Standardized Patients don’t only act as patients but as caregivers to patients, adding a whole new dynamic to scenarios.
7
t’s the words of one particular refugee that Dr. Gabriel Fabreau, BSc’04, MD’08, always comes back to, the words his father spoke to him the day he graduated from his academic fellowship at Harvard Medical School.
involved with the Mosaic Refugee Health Clinic in Calgary in 2012. Now, apart from seeing patients at the clinic, he is also leading a program of research he hopes will improve refugee care in Calgary and across the country.
“I’m immensely grateful to Canada,” his father said. “It gave us a home when we had nowhere to go . . . and you should be too, Gaby. Never forget that this country helped raise you, and now that you have the opportunity, it’s your responsibility to give back.”
Fabreau says the current Canadian guidelines on refugee and new-immigrant health care are based on a one-sizefits-all approach. But the emerging field of precision medicine as applied to community health presents a promising opportunity to streamline and improve the care of refugees, no matter who they are or where they come from.
Fabreau’s parents arrived in Canada as political refugees in the late 1970’s after fleeing a violent military dictatorship in their native Uruguay. He says because of this he always knew he wanted to work in refugee health care. “I empathize with the experience the refugees are going through and I know it’s very, very difficult because I watched my parents go through it,” says Fabreau. “I look at the kids that I see in the clinic and I think, ‘I was you 30 years ago.’” Fabreau, a clinical assistant professor at the Cumming School of Medicine, internal medicine physician and O’Brien Institute for Public Health member, got
“In terms of health care, refugees coming to Canada have been treated as one group, mostly due to lack of sufficient refugee health data,” he says. “But, on the ground, a Burmese refugee is nothing like an Eritrean refugee, who is nothing like a Syrian refugee, other than they’re all fleeing from something terrible.” Fabreau hopes his research, analyzing data from a cohort of 3,000 refugees the clinic has treated from 2011 to 2015, will help allocate the right resources up front, streamlining and improving care for patients regardless of where they come from.
“Right now there are a lot of questions around how best to care for different subpopulations of refugees, and what their needs are,” says Fabreau. “We’re working to understand what a well-functioning medical home needs for refugees patients: what are the specialties that should be embedded, what are the community partnerships we need, who are the multidisciplinary staff that need to be there, and how best to improve the quality and efficiency of care.” More than 2,500 patients are currently treated at the clinic. Fabreau urges anyone who may know of any privately sponsored refugees in the city to direct them to the clinic, which is equipped to provide the appropriate care, screening and resources needed for a successful start in their new country. The clinic, which has been operating in Calgary since 2003, cares for refugees and refugee claimants, including rejected refugee claimants, asylum-seekers, privately sponsored refugees and government-sponsored refugees within the first two years of their arrival. For more information visit: mosaicpcn.ca/Programs/Pages/RefugeeHealth-Clinic.aspx
9
A new approach by research clinicians to help children with rare diseases By Laura Herperger
ne in four children admitted to the Alberta Children’s Hospital (ACH) has an unknown or undiagnosed illness, presenting a particular challenge for both clinicians and families. These children often undergo many invasive tests without receiving a clear diagnosis. The rarer the disease, so is the information on its nature and outcomes. Now, families who have exhausted current testing can be directed to a new translational research program at ACH called KidOmics (a blending of the words “kids” and “genomics”). Here, families are presented with a precision medicine approach
– a powerful new way to diagnose an illness by taking into account a person’s individual genes, environment and lifestyle. This developing and innovative approach is providing rapid diagnosis, as well as individualized and tailored therapies for more and more children. In practice, KidOmics unites the clinicians who provide the care of children with developmental biologists and bioinformaticians who study the mechanisms of childhood diseases at the molecular level. “KidOmics means that we will be able to provide more patients and their families with a diagnosis, thus allowing for targeted treatment and accurate counselling,” says Jillian Parboosingh, PhD, BSc’88, associate professor in the
10
nucleotide, asking, ‘Does this nucleotide differ from the reference sequence?’ and, ‘Could this difference be the cause of this patient’s symptoms?’ I could not have imagined that we would be able to sequence and analyze all the approximately 5,000 genes that are currently known to be disease-causing, or even the 20,000 genes in our genomes in the automated fashion we do today.”
Department of Medical Genetics at the Cumming School of Medicine, and a member of the Alberta Children’s Hospital Research Institute (ACHRI). “It also means that, by working with a multi-disciplinary team of researchers, we can continue to discover links between diseases and genes, as well as new treatments. And, while doing so, we will learn how best to do this in a health-care setting.” When Parboosingh began her career 13 years ago, deciphering DNA was a slow and expensive process. Things however, have changed. “When DNA sequencing was first introduced into the lab, we would spend hours analyzing a single gene for one patient,” she says. “It was a very manual process looking at every single
The Calgary group has contributed significantly to approximately 400 investigations referred by pediatric centres across Canada. Half of these cases were solved and 60 novel genes were identified. They are also a part of a bigger national initiative and worldwide awareness campaign to find the causes of unknown childhood diseases. The World Health Organization and the International Rare Diseases Research Consortium have recently both stressed the need to improve the lives of children with birth defects and rare disorders. Through fundamental research, more and more common diseases once thought of as a single condition have become identified as dozens of distinct rare conditions, making diagnosis even more challenging. In the next three years, the KidOmics team plans to expand its investigations to 1,000 patients and will include
children with more common diseases such as cystic fibrosis, patients with rare congenital diseases such as Noonan Syndrome, and patients who are still classified as having an unknown cause of illness. They will also develop clinical trials with basic molecular scientists and bioinformaticians at ACHRI through a bed-to-bench modality. The KidOmics program positions Alberta to excel in the identification and diagnosis of rare childhood diseases in Canada. This vision is exciting for Parboosingh. “The current testing approach is antiquated and expensive for the healthcare system,” she says. “Cheaper, better technology exists and we need to harness it to improve outcomes now and in the future for Albertans.” Jillian Parboosingh and her colleagues are building upon FORGE Canada and the Care for Rare network, which are national projects supported by the Canadian Institutes of Health Research (CIHR), using advanced technologies to identify genes of rare disorders.
By Christina Hirota, PhD
For patients with inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, daily life can be unpredictable. These chronic, incurable diseases manifest differently in each patient and treatment options are limited.
ne type of targeted drug therapy, called anti-tumor necrosis factor (anti-TNF), is currently in use for IBD. TNF is an inflammatory protein in the body and is subsequently inhibited by anti-TNF. Unfortunately, one third of patients do not respond to this therapy and many for whom the treatment initially works eventually lose response. With new targeted therapies on the horizon, physicians face a more complicated challenge of picking the right treatment for the right patient at the right time. The lab of Dr. Subrata Ghosh is investigating the use of biomarkers to predict response to targeted therapies such as anti-TNF. This will offer patients a tailored “precision” approach to therapy by matching the treatment to each patient’s specific profile. Biomarkers are obtained through tissue that is easily collected through endoscopies. Endoscopies are routine procedure for both disease monitoring and screening, so no additional patient discomfort is created. Using these samples, the lab has been measuring a panel of 89 different genes in part of the gastrointestinal tract of patients with and without IBD. The genes expressed in these tissue biopsies paint a very detailed picture of the processes responsible for localized inflammation. Researchers have already found that a few of these genes may predict whether certain patients will respond to anti-TNF and they are currently working to validate these results using additional samples and methods. If a handful of genes are truly predictive of anti-TNF response, they envision that all patients will be screened for these biomarkers prior to initiation of this therapy. In addition, the team is also hoping to test similar panels of genes as possible predictors of response to other targeted therapies that are on the horizon. Dr. Subrata Ghosh is a professor in the Department of Medicine and member of the university’s Snyder Institute for Chronic Diseases.
A critical feature of the Precision Medicine Clinical Program will be an information -technology infrastructure that includes an electronic medical record for patient care and the functionality to conduct research. Standardized clinical phenotyping, and conventional and advanced diagnostic evaluation, will be developed in a diseasespecific manner. This program stream will also rely on the strong imaging and biobanking capabilities currently in existence within the Snyder Institute for Chronic Diseases and partnerships have already been created with Mitogen Advanced Diagnostics to obtain rapid results for a number of clinical tests. Research will capitalize on data and specimen collection through the clinic to understand disease pathogenesis, develop novel diagnostic, prognostic, and predictive assays, and evaluate therapeutic efficacy and disease outcomes. Clinicians and researchers learn more about models and pathways that are applicable in many other areas of medicine. The Precision Medicine Clinical Program will also provide education and knowledge-translation opportunities for stakeholders and end users that include patients, referring physicians, funding agencies and the community. ach year a specialist may see hundreds of patients, that have either presented themselves or have been referred from a primary-care physician, with severe inflammatory or complex immunological diseases. Often, these diseases are resistant to conventional treatment regimens and require multidisciplinary care. Furthermore, a clear diagnosis is frequently elusive for these patients or their condition is so rare that few specialists have the prerequisite experience. Current care pathways for these patients attempt to use all known medicines before turning to more unconventional diagnostic or therapeutic strategies that only then attempt to uncover and target a specific disease pathway.
Dr. Dan Muruve, along with Dr. Susanne Benseler, proposed the creation of a multidisciplinary Precision Medicine Clinical Program for Complex Immune Diseases. Specific patients are referred for in-depth, specialty-specific clinical and diagnostic evaluation using leading-edge technology to create personalized patient profiles used to inform treatment decisions. “This Precision Medicine Clinical Program is the combination of passionate clinicians, innovative researchers and a high level of knowledge of mechanisms on both the bedside and the bench,” says Muruve. “Our goal is to create optimal treatment plans based on the patient’s clinical, molecular and genetic profile.”
“This is about revolutionizing the way we think about medicine,” says Muruve. “Early recognition and early diagnostic evaluation is key if you want to prevent and possibly reverse chronic diseases. This Precision Medicine Program will ensure patients see the right expert at the right time and get the right diagnostics applied to their disease to get tailored treatment specifically for them.” Dr. Dan Muruve is a Professor in the Department of Medicine and member of the university’s Snyder Institute for Chronic Diseases. Dr. Susanne Benseler is Section Chief of Rheumatology, Department of Paediatrics, and a member of the university’s Alberta Children’s Hospital Research Institute and McCaig Institute for Bone and Joint Health.
n autoimmune diseases such as lupus, inflammatory bowel disease and rheumatoid arthritis, the immune system mistakenly attacks parts of the body it is designed to protect. These diseases are difficult to diagnose as the symptoms are often slow to develop and can be very similar to other conditions. For instance, lupus can affect many parts of the body including the joints, skin, kidneys, heart, lungs, blood vessels and nervous system. People can have the disease for years before it is properly identified, and often, damage to internal organs has already occurred by the time a diagnosis is made. A Cumming School of Medicine research team led by Dr. Marvin Fritzler, PhD’71, MD’74, a member of the university’s McCaig Institute for Bone and Joint Health and the Snyder Institute for Chronic Diseases, has developed a series of blood tests that provide a specific immune fingerprint of these diseases. This fingerprint allows physicians to diagnose lupus, rheumatoid arthritis and other inflammatory and autoimmune diseases at a much earlier stage in their development. In the 1970’s, Fritzler discovered several specific antibody biomarkers (measurable biological indicators) for lupus that led to the development of blood serum tests to diagnose the disease. When he was recruited to the University of Calgary in 1978, his lab was asked to set up diagnostic testing not just for lupus, but other rheumatic and autoimmune diseases. In 1986, he started a company, Mitogen Advanced Diagnostics Laboratory, and today it analyzes in excess of 50,000 serum samples a year from Alberta and around the world. “We get the blood serum samples and perform advanced blood tests that can identify up to 100 components at a time for each condition,” Fritzler says. “This provides an immune fingerprint of the patient.”
Fritzler says the analysis can be completed in a few hours with just a small drop of blood. The analysis gives physicians information on more than 50 different autoimmune conditions, thereby leading to early and accurate diagnosis. Physicians can also use the information to decide on the best therapeutic option for each individual patient. Once the specific disease is identified, targeted treatment can begin to prevent or slow its progression. “Because we are providing a very specific fingerprint of the immune system, this gives physicians a much better idea of which treatment is going to be most effective,” says Fritzler. “This will take away a lot of the ‘trial and error’ or ‘one-size-fits-all’ approach to patient management when physicians are trying to decide on the most effective and economical medications for a patient.” Fritzler and his colleagues are now working on a new blood test to identify specific proteins that regulate immunity and inflammation called cytokines. “Cytokine analysis will add more information to the clinical picture. It will help us predict disease much earlier, before the damage happens, maybe even before symptoms occur,” says Fritzler. “That means saving not just time and preventing patient suffering, but, for each patient, up to tens of thousands of dollars to the healthcare system each year.”
n her late 40’s, Elaine Pease, a retired floral designer, was told she had one of the worst set of lungs her doctors had ever seen. She had thought it was just a bad cold, brushed it off and had blamed it on the dry weather. It wasn’t long before she learned she had a debilitating journey ahead of her. She was diagnosed with severe asthma. “I think the moment that I knew my life had changed was when my grandson wanted me to lift him up, and I simply couldn’t,” says Pease, who got colds frequently but was extremely healthy otherwise. From the point of her diagnoses on, Pease’s life turned into a constant battle. She went from shopping, playing with her grandkids and working full-time to having walking, laughing and even breathing prove to be a challenge. “I remember when my asthma was at its worst I couldn’t even walk up the stairs in my own home,” she says. “I thought to myself, ‘Is this now my life? How can I possibly go on like this?’”
Asthma, which affects 15 per cent of the population, is a common chronic lung disorder in which inflammation causes the airways to constrict too much and too quickly, after exposures to a variety of environmental agents such as cat dander and pollens, things that have little or no effect in healthy people. This airway narrowing and inflammation results in breathing difficulties that may range from mild to life-threatening. Symptoms may include shortness of breath, cough, wheezing, and chest tightness that, in severe cases, can progress to respiratory failure and death. When Pease was first diagnosed over 20 years ago, she was treated like most other asthma patients with regular inhalers and medications. While her symptoms did improve somewhat, the asthma remained uncontrolled. “Breathing is something people take for granted,” she says. “It’s a function of your body that no one thinks about. It felt like I had lost a limb – I wasn’t sure how much longer I could live like this.”
Dr. Richard Leigh, professor in the Department of Medicine in the Cumming School of Medicine and member of the university’s Snyder Institute for Chronic Diseases, met Pease and realized “standard of practice” asthma treatments weren’t working for her. “We have inhaler therapies that are beneficial for those diagnosed with mild to moderate asthma, but those therapies don’t necessarily work for every person with the condition,” he says. “Asthma is not a single, homogeneous entity, and different patients benefit from different treatments so we decided to take a new approach for Elaine. It’s a question of finding the right treatment for the right patient at the right time, which is the basic premise of precision medicine.” Using this precision medicine approach, Leigh took individual asthma phenotypes into account, including variation of genes, environment, the type of inflammation present, lifestyle, and even in the microscopic organisms that were living inside of her.
“We were actually able to accurately phenotype Elaine based on the nature of her airway inflammation with various tests, allowing us to confirm that she has a phenotype of asthma termed late-onset, eosinophilic asthma,” says Leigh. “As the name implies, this sub-type of asthma occurs later in life and is characterized by eosinophils (a type of white blood cell commonly implicated in allergic response) in the inflamed airway. Moreover, this form of asthma is relatively resistant to the usual anti -inflammatory inhaler therapies that are generally prescribed for all asthma patients.
Leigh says this type of precision medicine approach is what will lead to better diagnoses, early interventions, moreefficient drug therapies and customized treatment plans, not only for asthma but for many chronic inflammatory diseases such as inflammatory bowel disease, chronic kidney disease and rheumatoid arthritis.
“Power of thought goes a long way,” she says. “Even when things got bad, I put faith in my doctors and maintained a positive outlook on the future. I can’t tell you how grateful I am to finally feel myself again.” As the ability to analyze and integrate patient characteristics increases, what can be expected is faster and broader implementation of precision medicine not only with asthma, but across the spectrum.
“Using biomarker discovery and disease phenotyping in the lab will have a huge clinical impact,” he says. “Using biomarkers, “This approach can change the future of we can better diagnose each patient and airway-disease management in Alberta and then categorize individual patients into a one day we hope that every patient can precision medicine approach depending feel the way that Elaine does,” says Leigh. on their phenotype and genotype results. In the future we hope to phenotype and “Because of the presence of eosinophils in Dr. Leigh is also the GSK-CIHR Professor of her airways, we could specifically treat her genotype every patient that walks through Inflammatory Lung Disease at the University that door, which will allow us to better with a novel drug that precisely targets of Calgary. predict which patients respond to which the inflammation.” This precision medicine approach is utilized specific medications.” After years of poor health on conventional as part of research in the Snyder Institute for asthma treatments, Pease says her life has Pease now enjoys spending time with her Chronic Diseases in the TAMARATT Lung Suite. grandkids, participating in craft fairs and been transformed by this therapy. is back to work part-time in a flower shop. “I don’t think there is anything better than Through it all, her bubbly personality and clear lungs,” she says. “Dr. Leigh and his zest for life is also what helped through the team have absolutely changed my life. I hard times she endured. went from simply existing, to living again.”
he typical treatment of cancer currently involves a combination of radiation, surgery and chemotherapy. It’s an imperfect, but broadly applied approach that often leads to difficult side-effects. The tumour may be neutralized, but many of the healthy cells around it can be negatively affected. It’s a bit like using a Phillips bit on a Robertson head — the screwdriver may still work, but there’s a chance you’ll strip your screw in the process. With better and precise approaches, more can be accomplished, and more efficiently. Cancer requires a hefty toolbox. It’s not just one disease, it’s actually many subtypes under the umbrella of the “cancer” label — many subtypes now identifiable through specific DNA signatures. And thanks to precision medicine, using our growing knowledge of genetics offers a better way to prevent and treat cancer. “It’s an enormously complex disease. Breast cancer is clearly different to brain cancer, but even within one cancer there are
“If we can design drugs or treatments that only target the specific tumour, there should be fewer side effects to the normal cells in the body.”
distinct sub-types. Over the last 10 years or so, we’ve been able to categorize cancer based on its genetics and genetic profile,” says Susan Lees-Miller, PhD, who leads an exceptional team of investigators in the University of Calgary, Cumming School of Medicine’s (CSM) Arnie Charbonneau Cancer Institute. “With this new knowledge and understanding, we can start tailoring solutions or therapies to the specific type of cancer. By understanding the unique DNA profile of a particular type of cancer, we can design treatments that specifically target that cancer.” Lees-Miller and her team are working to exploit specific differences in the tumour cell’s ability to detect and repair damaged DNA. With her collaborator Dr. Gwyn Bebb, an associate professor in UCalgary’s Department of Oncology and a Charbonneau member, Lees-Miller has shown that tumour cells deficient in a protein called ATM are sensitive to a new type of therapeutic drug called a PARP inhibitor. With this knowledge, it may be possible to screen cancer patients to discover whether their tumours are
missing ATM, making them receptive to treatment with the inhibitor drug. “That’s the goal of precision medicine, being able to understand the genetics, the DNA profile of the different cancers so that you can specifically tailor the treatment to that cancer,” says Lees-Miller. Being able to strike at the disease with that kind of accuracy would be preferable to the current use of treatments like radiation. The radiation meant to kill cancer is focused on the tumour, but there is inevitably damage done to the healthy tissue around it. This leads to an increase of side effects that occur after current cancer treatment — which may even include a second cancer. Better outcomes are possible with personalized approaches that focus on the DNA signature of a tumour to help customize treatment. “If we can design drugs or treatments that only target the specific tumour, there should be fewer side effects to the normal cells in the body,” says Lees-Miller. “And
that’s really the goal, to kill more of the cancer cells and cause less damage to normal cells.” Lees-Miller and her team are part of the Robson DNA Science Centre, a basic science research centre focusing on the study of DNA damage and repair. The centre was made possible thanks to a $10-million gift by Dave and Val Robson, through the Calgary Foundation. “I think we’re incredibly fortunate to be working in biomedical science now when so many amazing discoveries are being made,” says Lees-Miller. “I see genomics as a real milestone in biomedical research. It’s really going to pay dividends for many years to come.” Susan Lees-Miller,PhD, is a professor in the CSM’s departments of biochemistry and molecular biology, and oncology.
share with you what I’ve termed, really, an evolution in the treatment of breast cancer. It can’t be called a revolution because we still have one in 10 women who get diagnosed with breast cancer during their lifetime. We still have 5,300 women who die of breast cancer every year in Canada and we still have about 4,000 women who get diagnosed with breast cancer every year in Canada. So I think it would be an injustice to all those women, all those patients, all those health-care workers who are treating the disease, if you call this a revolution… Overall in HER 2-positive breast cancer we have nearly doubled, tripled, how long patients with advanced HER 2-positive cancer will live. We were able to show that, if we offer targeted therapies to our patients, they live longer, they live better and some of them with less side effects. However, many of them will still die of this disease. Many of them will still have cancer that mutates and cancer that is going to progress. And the question then is: why do we have to wait for cancer to be advanced for us to be able to treat
them? Can we treat them early? Can we treat them right when they have breast cancer in the early stages and not in the advanced stages? How do we offer precision medicine early on? Well, the challenge is, in most patients with breast cancer, this is what we do: we send them to surgery, after surgery we give them chemotherapy and after chemotherapy we may give them radiation and targeted drugs. Well, that doesn’t quite make sense because we take away the tumour and our goal then is to give targeted chemotherapy to any small cells which are floating around. But we don’t really know if it’s working or not because the tumour has been taken away. Well, what if we gave the treatment even before surgery and we could see if the treatment was working, if the cancer was shrinking? Well, what if the patient would not have to go through hair loss, nausea and vomiting, risk of infection and we just target the treatment right before surgery? And what if we send the patient to surgery and there are no more cancer cells left? So this is really switching our mindset. Instead of thinking as soon as we see cancer we have to go and rush
into surgery and then give the treatment afterwards, what if we step back and understand what is it that’s making the tumour grow? What if we give it a total, targeted approach? And what if, with this total, targeted approach without the chemotherapy, if the patient goes through surgery and there’s no cancer cells? Well what we know, if that’s the case, these patients do really well. The challenge is, how do we change the dogma and how do we reverse the sequence so we can start offering targeted treatments earlier and earlier, and what if we had a way of measuring and imaging if the tumour cells were melting away and these patients didn’t even have to go through surgery? That is precision medicine and that is what the future of HER 2-positive breast cancer will look like. Dr. Sunil Verma is a professor and head of the university’s Department of Oncology. For more information on the dean’s talks visit: http://cumming.ucalgary.ca/deans-talks
21
Rod Crutcher received an email in 2005 about African physicians from what is now the Republic of South Sudan. As refugees in Canada, they wanted the Cumming School of Medicine (CSM) to upgrade their training so they could return to help rebuild their war-torn home country – the reason they had left as children in the 1980’s. “Their medical skills were rusty and their English skills were varied, but it became clear they wanted to serve their people,” says Crutcher, a professor emeritus who at the time was director of the Alberta International Medical Graduate Program. “I got to know them and I thought: ‘You know, maybe we can help them.’” Decades of civil war had left South Sudan facing everything from ethnic violence
to a lack of roads. Although it gained independence from Sudan in 2011, it will likely take years for the country to recover. Moved by the doctors’ resolve not to settle for a comfortable life in Canada, Crutcher not only became the director of the Sudanese Physician Reintegration Program at the CSM from 2006 to 2015, he currently volunteers as chair of an advisory committee for the South Sudan Education Fund. It gave more than $30,000 in 2015 to support the physicians’ ongoing medical training, as well as the education of their children. The scholarship was founded in 2014 in memory of Dr. Thomas Lul Kuagien. Recently married, he was murdered in 2013 along with many of his hospital patients during a rebel attack.
22
He had originally been one of about 600 youths – many of them child soldiers – sent to Cuba in the 1980’s, says Crutcher. “The leader of the Sudanese People’s Liberation Army held out a pencil and told them to put down their guns and get educated, and when the time was right, to come back and rebuild their country,” he says. Although 25 of them earned medical degrees in Cuba, they lacked clinical training, says Crutcher. As a result, the CSM partnered with Samaritan’s Purse Canada to create the Sudanese Physician Reintegration Program. Under Phase 1 in 2006, 15 of the physicians upgraded their skills for nine months in Calgary, taking everything from tropical medicine to English. Phase 2 involved up to 18 months of clinical training in Kenya.
With funding from the Canadian International Development Agency, the Southern Sudan Healthcare Accessibility, Rehabilitation and Education (SSHARE) program commenced in 2009 to support the physicians by improving medical facilities. The CSM also continued its training until the funding ended in 2013 and the program accomplished its goal of giving the doctors the skills they needed to practice medicine in their homeland. Treating up to hundreds of patients per day in a nation with the worst reported maternal mortality rate in the world, the physicians face years of struggle. But they have been given some needed support. “We showed we can be a model for doing good in a fragile part of the world through education,” says Crutcher. “We did what we set out to do. We are proud to count
as friends and colleagues our South Sudanese brothers and sisters, who carry on providing health care to some of the poorest of the poor.”
To donate to the scholarship, visit netcommunity.ucalgary. ca/SouthSudanEducationFund
By Laura Herperger
aiya MacLean is a bubbly, curious 10- year-old with a big smile. Her passion is swimming. She is a competitive swimmer, in the pool four hours a week, with a team called the Sting Rays. But it wasn’t always easy for this happy-go-lucky young girl. Taiya was diagnosed and treated for AML leukemia, a rare form of cancer, four years ago. She and her family, including parents Amanda and Chad, have made the trip from their home in Okotoks to visit her oncologist at the Alberta Children’s Hospital many, many times. When they initially received the diagnosis, Amanda reacted with nothing but positive hope. “I just said to myself, we can do this,” she recalls. Taiya is now completely healthy. As a big component of her therapy, she received a stem-cell transplant to help restore her immune system that had been suppressed as a result of the chemotherapy and radiation she had undergone. Stem cells are obtained from a donor’s blood or bone marrow and are infused into the recipient. “Taiya had little to no reaction to the transplant. I think she got a fever, but it was manageable,” says Amanda, adding that the stem cells her child received came from the blood of an unrelated donor — a young woman from Poland. “I remember it being a very exciting day for us. When the cells arrived at the Alberta Children’s Hospital (ACH), it was such a buzz. They were here! They were in the building! We celebrated with a piñata.” Over the last 10 years, approximately 200 children received similar transplants at ACH. A University of Calgary research team has combed the data from these procedures, examining the results of the therapy to determine how children react to the transplant. There are few studies and scant literature globally examining stem cell-infusion reactions in a pediatric population. “We were pleased to see that most of the children, nine out of 10, did extremely well with this procedure. No child in our study had any severe or life-threatening reactions,” says study lead Dr. Tony Truong, an assistant professor in the departments
of oncology and paediatrics at the Cumming School of Medicine, and a member of the Alberta Children’s Hospital Research Institute. According to the study, published in the January 2016 edition of the journal Bone Marrow Transplantation, only 11 per cent of children suffered moderate adverse reactions, with hypoxia (low blood oxygen) and high blood pressure being the most common. These symptoms were easily treated and resolved within a few hours. All other reactions were considered mild, with fever and nausea being the most common. Unlike the adult population in similar studies, children tolerated a higher level of mature white blood cells, a component that tends to accompany the stem cells during these infusions. “This tells us that the physiology of children is much different than adults when it comes to blood and marrow transplantation,” says Truong. “This difference, along with other important disease and treatment factors, allows them to tolerate these procedures much more easily to the benefit of health outcomes.” Publications on similar studies in adults show almost twice as many moderate adverse reactions, usually cardio-pulmonary, with a few adults suffering a heart attack. The U.S. National Cancer Institute has established a universal reporting system for adverse reactions to which all researchers adhere in their studies. Truong found that receiving stem cells from a donor, whether related or not, had double the risk of an adverse reaction (46 versus 26 per cent) compared to autologous stem-cell transplants that involve taking stem cells from oneself and receiving them back later. The research team also noted that cord blood, also a source for stem cells, was slightly less tolerated in children. Overall, laboratory processing of the stem cells before it reaches the patient, such as washing, reducing extra red blood cells or extra plasma, significantly reduced the risk of adverse reactions. For the MacLean family, they are grateful the procedure led to a healthy recovery of their child. “For Taiya, it was life-saving” says the mom. If you wish to become a stem cell donor, contact Canadian Blood Services’ OneMatch at blood.ca.
Yoho Tranquility Magnetic performance
t is often said that people see life through the perspective of their particular lens—but for Dr. Scott Forsyth, lenses and perspectives have quite literally been his focus and passion for years. Forsyth, MD’99, a family doctor with a practice in Calgary, was exposed to drawing and painting at a young age by his grandmother, who was a landscape painter. Faced with the choice of art school or a science degree, he chose the latter but managed to maintain a strong connection to art. Scott Forsyth
“Ironically, it was during my medical training that I transitioned from drawing and painting to photography,” he says. “I was determined early on to carve a pathway into professional photography
alongside a medical practice, and it influenced my choice of medical speciality. I needed to have autonomy over my time and practice in order to accommodate the requirements of travel.“ Forsyth’s keen eye and stunning photography has netted him several prestigious awards and accolades. Among many prestigious awards, he was recently named a Fellow of the Royal Canadian Geographical Society (RCGS) — an honour in which he is most proud. “As I developed my photographic activity I chose to focus on the Canadian landscape, to represent Canada to Canadians, and to become better acquainted with my own country,” he says. This turns out to match the mission of [the RCGS publication] Canadian Geographic: ‘To make Canada
Remnants of time
Symetrical Serenity
better known to Canadians and to the world.’ I now feel like my mission is part of a larger society and I look forward to collaborating through the coming years.� Working with Adventure Canada, Forsyth is keen to impart his knowledge of photographing the Canadian landscape to others through hands-on learning and immersive travel programs. These unique opportunities allow lifelong learners the opportunity to explore coastal environments and local culture with the guidance of geologists, authors, naturalists and, of course, photographers. Forsyth’s accomplishments as a photographer are mirrored by his work as a respected family physician. An active clinician, he sits on the board of directors for the Calgary West Central Primary
Care Network, is a civil aviation medical examiner for the Ministry of Transport and is a clinical lecturer for the Cumming School of Medicine. He believes strongly that art and medicine have more synergy than is commonly thought. Pointing out that experienced physicians, like artists, engage their right hemispheres when making clinical decisions, he is clearly an artist who is deeply connected with both the science and art of Medicine. scottforsyth.ca
ou’ve completed your PhD and postdoctoral training, but what comes next? Naweed Syed, PhD, postdoctoral program director in the office of UCalgary’s Vice President, Research, estimates only 10 per cent of these individuals will go on to secure positions in academia. As part of a pilot project in 2014, Syed created a mock faculty position competition to better prepare these individuals for academic positions. With 34 University of Calgary postdoctoral scholars submitting portfolios, the top three finalists, as selected by a committee comprised of Cumming School of Medicine (CSM) faculty members, partook in a “real-world” search and selection. Syed sits down with us to discuss the impact of this project, which was also recently published in the journal Academic Medicine. Why did you initiate this project? We must set our trainees up for success in their respective careers. A lot of trainees never make it to a short list, let alone an interview, so we wanted to simulate a real “search and selection” scenario to expose our trainees to the real thing. It was also a good opportunity for us as a faculty to determine the calibre of our postdocs and the CSM’s preparedness to offer such innovative professional developmental programs. Why do so few post doc fellows pursue a career in academia? I think many of our trainees believe that publications would suffice for them to secure a job in academia. They do not
a candidate or an observer. Independent of the search and selection committee, the audience also got to play an active role in evaluating the candidates. What did participants take from this experience? The winner received a $10,000 award and everyone who applied received personalized feedback on their application and presentations. I’d also like to point out that our winner went on to secure a position at UBC (University of British Columbia), whereas the runner-up Rita Henderson, PhD, wrote this study for publication as a first author. She has also been invited to present this program at an international conference in the UK. We have the best and the brightest trainees and we hope that they will remain a part of our university family for years to come. however appreciate what the university is looking for in a faculty member. One of our goals was to make our postdocs recognize the holistic attributes that one needs to exhibit to secure an academic position. What happened during the mock interview? All CSM postdocs were invited to apply for a “Mock Academic Position” and asked to submit their CV and a research summary. The panel then reviewed the documents and the top three applicants were invited to give research talks and participate in a face-to-face interview, the proceedings of which were projected live to an auditorium of 70 trainees. All CSM faculty, staff and students were invited to attend the session, and by extending this opportunity to an audience, we allowed for all participants to learn through this experience, whether as
What advice do you have for our trainees? As they say, “success is a habit.’’ I would add that courage is the doorway to that success. Our trainees need to make sure that they have confidence in their abilities to put themselves out there in such competitions and to seek out mentorship and professional career opportunities that are offered by the postdoctoral program. Naweed Syed, PhD, is a professor in the Department of Cell Biology and Anatomy and the Scientific Director of the Alberta Children’s Hospital Research Institute. Jonathan Lytton, PhD, head of the Department of Biochemistry and Molecular Biology moderated the preceedings. Gerald Zamponi, PhD, Senior Associate Dean, Research, chaired the selection committee.
n animal study by the Hotchkiss Brain Institute (HBI) provides new insight into how high-fat diets rapidly rewire the reward circuits in the brain, which can lead to an increase in foodseeking and risk-taking behaviours in the pursuit of food. The study, published in Proceedings of the National Academy of Sciences of the United States, could contribute to the understanding of what underlies the development, and implications, of overeating.
he decision to stop adding fluoride to drinking water in Calgary five years ago has had a negative impact on children’s oral health, says a study that compared grade two students in Calgary and Edmonton. The UCalgary-led study, published in Community Dentistry and Oral Epidemiology, showed that in primary (baby) teeth there was a worsening in tooth decay in Calgary since fluoridation ended in in 2011, compared to Edmonton, where water is still fluoridated. In fact, the number of tooth surfaces with decay per child increased by 3.8 surfaces in Calgary during the time frame of the study (the 2003-2004 and 2013-2014 school years), compared to only 2.1 in Edmonton. This is considered a statistically significant difference, as,
the average child has about 20 teeth with four or five surfaces per tooth. Fluoride is a tooth-enamel-strengthening mineral that was first introduced into public drinking water in 1945, with Calgary starting to add it in 1991. The debate in North American communities over whether or not to stop fluoridating water has been ongoing for years. There are currently few published studies that look at the effects of fluoridation cessation. Researchers from the paper hope their study can be explored by decision-makers who are involved in these discussions. Lead Author: Lindsay McLaren, PhD, BSc’00, associate professor, O’Brien Institute for Public Health, Department of Community Health Sciences
Researchers observed that synaptic changes occurred in the ventral tegmental area (VTA), a region of the mid-brain that plays a central role in reward-seeking, when mice were exposed to a sweetened, high-fat food for a 24-hour period. In addition, the synaptic changes were observed for at least a week following the binge. The increase in synapses to the VTA dopamine neurons suggests the brain is being primed to want to eat more, despite hunger levels. While this study was conducted in animal models, the human brain has similar circuits that drive food intake. Senior author: Stephanie Borgland, PhD, associate professor, Department of Physiology and Pharmacology First Author: Shuai Liu, PhD, HBI postdoctoral research scholar
30
he discovery of a new signalling pathway in neurons could help researchers understand how to protect the brain during a stroke. Researchers have long thought that a protein called the NMDA receptor was principally responsible for neuron death during a stroke, but a new animal study shows that it is, in fact, the interaction between NMDA receptors and another protein known as pannexin-1 that
causes the neurons to die. The discovery was made at the Hotchkiss Brain Institute (HBI) at the Cumming School of Medicine and published in the journal Nature Neuroscience.
new study from the University of Calgary’s Snyder Institute for Chronic Diseases could change the way researchers understand and treat autoimmune diseases such as type 1 diabetes, multiple sclerosis and rheumatoid arthritis. The complexities of these diseases have made it very difficult to develop treatments that can stop disease without impairing normal immunity. Using animal models and human cells in animal models, researchers
at the Cumming School of Medicine have discovered a novel mechanism that stops the immune attack, and have developed a new class of drugs that harnesses this mechanism to treat various autoimmune diseases without compromising the entire immune system. The study was published in the journal Nature.
Senior Author: Roger Thompson, PhD, assistant professor, Department of Cell Biology and Anatomy First Author: Nicholas Weilinger, PhD , PhD’16
study out of the University of Calgary’s Cumming School of Medicine’s O’Brien Institute for Public Health has determined which sports pose the highest concussion risk to youth. The systematic review, which analyzed medical literature dating back to the 1980’s, was published in the British Journal of Sports Medicine. The study looked at 12 sports that included: rugby, lacrosse, soccer, hockey, football, wrestling, basketball, softball, baseball, cheerleading, volleyball and field hockey. Researchers were able to determine overall average concussion risk for youth to be 0.2 concussions per 1,000 athlete exposures (AE) — any single practice or game. The three sports with the overall highest risks were: rugby (four concussions per 1,000 AE), hockey (one concussion per 1,000 AE) and football (0.5 per 1,000 AE). The remaining nine sports had relatively low concussion risks. Senior Author: Paul Ronksley, PhD, PhD’13, assistant professor in the Department of Community Health Sciences
Senior Author: Dr. Pere Santamaria, professor, Department of Microbiology, Immunology and Infectious Diseases