5 CV: DR. MEAGHAN O’REILLY

6 TRAINEES’ POST

7 APPLAUSE

A Bevy of Funding Awards; It’s a Boy;Coming Soon: 2015 SRI Magazine2

SPRING 2015

Bringing Scientific Ideas to MarketFedDev Ontario investment to accelerate commercialization of innovative technologies at SRIBy Betty Zou Sunnybrook Research Institute (SRI) will receive a $41-million investment to support the commercialization of innovative technologies in image-guided therapeutics. The Honourable Gary Goodyear, minister of state for the Federal Economic Develop-ment Agency for Southern Ontario (FedDev Ontario), and John Carmichael, member of Parliament for Don Valley West, announced the funding at SRI on April 10, 2015.

“I’m pleased this investment will help Sunnybrook to solidify the image-guided therapy technology cluster it has strongly estab-lished. This will lead to the design and export of innovative new technologies and the creation of high-value jobs here in southern Ontario,” said Goodyear.

The $20-million investment from FedDev Ontario will be matched by a $21-million investment from industry partners as part of FedDev Ontario’s Investing in Commercialization Partnerships initiative. The program aims to address the innovation and commercialization gap between research institutions and the private sector by fostering partnerships between both sides.

Continued on page 3

L to R: MP Joe Daniel, Dr. Kullervo Hynynen, Dr. Michael Julius, Minister Gary Goodyear and MP John Carmichael celebrate FedDev Ontario’s investment in SRI. [Photo: Dale Roddick]

2 • Sunnybrook Research Institute

News @ SRIA Bevy of Funding Awards

Eight scientists working in the areas of brain, cancer, musculo-skeletal and trauma research at Sunnybrook Research Institute (SRI) secured funding in recent competitions.

Dr. Clare Atzema, a scientist in the Trauma, Emergency & Critical Care Research Program, received a one-year planning and dissemination grant worth $20,000 through the Institute of Community Support at the Canadian Institutes of Health Research. The funds will support her work on addressing the frequency and timeliness of follow-up care after a visit to the emergency department in patients with chronic disease.

The Physicians’ Services Incorporated Foundation awarded Dr. Stephen Choi, an affiliate scientist in the Holland Musculoskeletal Research Program, $17,000 over two years. His research will examine whether administering lidocaine and pregabalin before breast surgery can reduce post-mastectomy pain syndrome, a condition that affects up to 65% of patients. The pilot study aims to inform the feasibility of a larger multicen-tre, clinical trial. Choi also received $86,000 over 18 months to conduct a randomized controlled trial to compare the effects of administering perineural medications with a single dose of local anesthetic injected around the brachial plexus nerves prior to shoulder surgery.

Dr. Paul Karanicolas, a scientist in the Odette Cancer Research Program, received $90,500 over two years from the Physicians’ Services Incorporated Foundation. He will conduct a study to determine the effect of the drug tranexamic acid on blood loss and the need for a blood transfusion afterliver resection.

The Weston Brain Institute awarded Dr. Mario Masellis, an associate scientist in the Hurvitz Brain Sciences Research Program, $449,559 over three years. He will use the funds to develop a robust clinical trials platform to conduct a genomic-imaging analysis of the genetic frontotemporal dementia initia-tive. His research focuses on understanding the genetics of neurodegenerative and neuropsychiatric diseases, neuroimaging in dementias, and the pharmacogenetics of antipsychotics and cholinesterase inhibitors used to treat Alzheimer’s disease.

Dr. Claire McCann, an affiliate scientist in the Odette Cancer Research Program and medical director of Odette Cancer Centre Clinical Research, was awarded infrastructure funding worth $894,348 over four years from the Canadian Cancer Clinical Trials Network to support the work of the Odette Cancer Program clinical trials group at Sunnybrook.

Dr. Mark Rapoport, an associate scientist in the Hurvitz Brain Sciences Research Program, was awarded a one-year knowledge synthesis grant worth $100,000 from the Canadian Institutes of Health Research. He will use the funds to develop a collaborative international knowledge synthesis to update guide-lines for determining medical fitness to operate motor vehicles. His research focuses on neuropsychiatric sequelae of traumatic brain injury in the elderly and predictors of motor vehicle collisions in the elderly.

The Cancer Research Society awarded Dr. Arun Seth, a senior scientist in Biological Sciences, a 2014 operating grant of $120,000 over two years. His research will focus on microRNA signatures that are predictive of prostate cancer recurrence and metastasis.

The Canada Foundation for Innovation awarded Dr. Martin Yaffe, a senior scientist in the Odette Cancer Research Program, a John R. Evans Leaders Fund grant worth $203,352. He will use the funds to expand SRI’s integrated cancer research biomatrix. Dr. Paul Karanicolas

Coming Soon: 2015 SRI Magazine

Stories about the innovative research happening at Sunnybrook Research Institute (SRI) are featured in the 2015 SRI Magazine, Inventing the Future of Health Care. The annual publication is now in its ninth year.

This year’s issue contains a special section on the work of scientists and clinician-scientists in the Schulich Heart Research Program. These researchers are developing and evaluating new tools and interventions to understand and improve the care of people with a variety of heart conditions, and translating discov-eries into improvements in health care technology and practice.

You’ll also read how scientists at SRI are harnessing the power of the immune system to fight cancer, unlocking the mysteries of frontotemporal dementia and mentoring science trainees despite a challenging funding climate and job landscape.

Look for the magazine on newsstands and online at sunnybrook.ca/research.

It’s a Boy!

Baby Eliot Dae-Kwang Kim arrived almost a week later than expected for Alisa and her husband Ed Kim.

Alisa Kim, communications officer at Sunnybrook Research Institute, gave birth to a healthy baby boy on Feb. 20 at Sunnybrook’s Women & Babies birthing unit. Eliot weighed a hefty eight pounds, 10 ounces.

Big brother Jeremy is very excited to have a little brother. Mom, dad, Jeremy and their bundle of joy are all doing well.

Eliot Dae-Kwang Kim

NEXUS SPRING 2015 • 3

News @ SRI[P

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Continued from page 1

Building on the success of a previous $6.91-million investment from FedDev Ontario, SRI will use the funding to expand its image-guided therapy cluster and accelerate the commercialization of 28 innovative technologies. Collaborating with SRI in these ventures will be 28 industry partners and 32 nonprofit organizations including four universities: Western University, who was part of the previous FedDev award, Queen’s University, Ryerson University and University of Toronto.

The 28 new technologies fall into five specific areas within image-guided therapeutics: focused ultrasound, cardiovascular interventions, therapy response, musculoskeletal interventions and detection. These new technologies will improve patient care by making diagnostic and treatment procedures lessinvasive, more accurate and safer.

Following the speeches, Dr. Michael Julius, vice-president of research at SRI, escorted Minister Goodyear, Mr. Carmichael and Mr. Joe Daniel, member of Parliament for Don Valley East, to SRI’s device development lab for an in-depth look at two projects that will receive commercialization support from this investment. Read the full story at sunnybrook.ca/research.

MP John Carmichael announces SRI will receive $20-million in investment from FedDev Ontario to commercialize innovative technologies.

Inside the advanced machine shop, Dr. Michael Julius (right) shows MP John Carmichael (left), MP Joe Daniel (centre-back) and Minister Gary Goodyear (centre) the lathe used to create custom, small, high-precision parts for devices.

L to R: Minister Gary Goodyear, Dr. Kullervo Hynynen and MP John Carmichael look at the benchtop therapeutic ultrasound system developed by FUS Instruments.

Drs. Cari Whyne (left) and Oleh Antonyshyn (right) show some craniofacial moulds (pictured above) developed by Calavera Surgical Design Inc. to MP John Carmichael (centre-left) and Minister Gary Goodyear (centre-right).

4 • Sunnybrook Research Institute

Tool Kit: BioRad’s QX200 ddPCR System

Droplet digital polymerase chain reaction (ddPCR) offers highly sensitive detection and absolute quantification of target DNA or RNA molecules. BioRad’s QX200 ddPCR system combines water-oil emulsion droplet technology with microfluidics by first partitioning individual ddPCR reactions into 20,000 uniform nano-litre droplets. Following a standard PCR reaction, the droplets are streamed through the droplet reader for fluorescence analysis.

Droplets containing at least one copy of the target molecule will emit a higher fluorescence signal compared to negative droplets. The QuantSoft software applies statistical analyses to gener-ate an absolute quantification of the target molecules. Digital platforms like ddPCR are being used to identify cancer subtypes, optimize drug treatment designs, monitor residual disease and study tumour evolution.

Dr. Arun Seth, a senior scientist in Biological Sciences and director of the genomics facility at Sunnybrook Research Institute (SRI), says the advantage of ddPCR over real-time quantitative PCR is its sensitivity: “ddPCR provides absolute counting of target molecules, whereas the other methods give you relative expression. With ddPCR, you don’t need a standard curve.”

The QX200 system is compatible with both TaqMan hydrolysis probes and EvaGreen dye. While the droplet generator can pro-cess up to eight samples at a time, the assays can be scaled up for high-throughput using 96-well plates. By pooling samples, the sensitivity of the QX200 system can be increased to detect target molecules with concentrations as low as one in 1,000,000 copies.

Dr. Yutaka Amemiya is manager of the genomics facility and operates the system. “Most of the projects are cancer-related RNA expression studies,” he says. These include Seth’s research on microRNA biomarkers for prostate cancer and Dr. Wedad Hanna’s studies on detection of copy number amplification of HER2 in breast cancer. Dr. Michael Julius is developing ddPCR-based screening strategies for detecting CRISPR-Cas9 induced mutations in cell lines. The ddPCR platform is also suited for library quantification for next-generation sequencing and analysis of genetic mutations and copy number variations.

The QX200 is also a useful tool in microbiology, where Drs. Samira Mubareka and Andrew Simor are using it to quantify the viral loads of the flu virus and rhinovirus in biological samples.

The system is worth $100,000 and was purchased with funding from the Biological Sciences Platform at SRI. — Betty Zou

BioRad’s QX200 ddPCR system comprises the droplet reader (left) and the droplet generator (right). [Photo: Betty Zou]

Showcasing Investment in Research Infrastructure

On March 20, 2015, the Honourable Ed Holder, minister of state (science and technology), and John Carmichael, member of Parliament for Don Valley West, visited Sunnybrook Research Institute (SRI) for a tour of the Centre for Research in Image-Guided Therapeutics. Dr. Michael Julius, vice-president of research at SRI, and Malcolm Moffat, executive vice-president at Sunnybrook, hosted the guests.

The first stop was the high-content cellular analysis (HiCCA) lab managed by Dr. David Andrews, director of the Biological Sciences Platform at SRI. Jarkko Ylanko, a research technicianin the Andrews lab, demonstrated the Opera system, a high-content screening system that can take more than 100,000 images of cells a day. It is being used to advance research in precision medicine.

Next, Dr. Kullervo Hynynen, director of the Physical Sciences Platform, showed the focused ultrasound brain device he developed and commercialized in collaboration with industry. The device is being tested clinically for noninvasive treatment of essential tremor, Parkinson’s disease and brain cancer.

The tour ended inside the Neurointervention Centre. Dr. Brad MacIntosh, a scientist in Physical Sciences, and Dr. Sandra Black, director of the Hurvitz Brain Sciences Research Program, discussed their work using imaging to detect dementia in asymptomatic individuals.

L to R: MP John Carmichael, Minister Ed Holder, Jarkko Ylanko, Dr. Michael Julius and Malcolm Moffat inside the HiCCA lab. [Photo: Doug Nicholson]

NEXUS SPRING 2015 • 5

We Are SRICV: Dr. Meaghan O’Reilly

Bio basics: A scientist in Physical Sciences and the Holland Musculoskel-etal Research Program at Sunnybrook Research Institute (SRI) and assistant professor at the University of Toronto. Completed her PhD in applied physics at the University of Eastern Finland; a M.Sc. in biomedical engineering at the University of Oxford in the U.K. and a B.Sc. in mechanical engineering at Queen’s University. Grew up in Scarbor-ough, ON with four brothers and a sister.

As a former research associate at SRI, how does it feel to be appointed a scientist?I’m looking forward to starting my own research group, which is equally exciting and a little frightening too. The spine is an interesting area for ultrasound therapy that has been sparsely investigated. There’s a lot of potential in taking the drug delivery work that we’re doing in the brain and applying it to the treatment of conditions like amyotrophic lateral sclerosis, spinal cord injury or spinal muscular atrophy.

What is your research focus?It’s centered around drug delivery applications in the brain with a focus on the physics and engineering aspects. We’re using ultrasound to facilitate drug penetration through the blood-brain-barrier, and the work has reached a stage where researchers are very close to implementing the technique in patients. There is an equivalent spinal cord barrier, but the geometry of the spinal col-umn is much more complex than the skull. Where it becomes very interesting from an engineering standpoint is how do we design systems and transducers to specifically target the spinal canal.

With whom do you collaborate at SRI?Through my work with Dr. Kullervo Hynynen, I’ve worked with Dr. Isabelle Aubert quite a bit. I’m looking forward to working with other scientists. The exciting part about being an indepen-dent investigator and starting out on your own is reaching out and using all the available resources.

Why SRI?The facilities are a step above anything that I’ve had access to in any other research position. I like that it’s a hospital-based research institute. You could do research at a university, but being right in the hospital, there’s a lot of integration with clinicians, as well as a lot of potential for translating the work and having it used in the clinic.

What interested you in becoming a researcher?What I really like about engineering is the problem solving. We’re doing new things that people haven’t thought of before. That sort of curiosity is what really makes me passionate about research.

If you were not a scientist, then which profession would you choose? That’s a tough question. I briefly considered applying to theatre programs. I have an associate diploma in speech and drama performance from Trinity College London. I really enjoyed that but I don’t think I could do it as a career.

What activities or hobbies do you enjoy outside of work? I’m a hockey player. This is what happens when you have brothers. I’m a cyclist and also a knitter and a hand-weaver.

What advice do you have for students and trainees in science?Work hard and find a research area that you’re passionate about because then it becomes very enjoyable.

Bio basics: Core facility manager, Centre for Flow Cytometry and Micros-copy at Sunnybrook Research Institute (SRI). Born in Trinidad and moved to Toronto at age nine. Completed her PhD in immunology at the University of Toronto. Graduated from McMaster University with an Hon. B.Sc. in biology and pharmacology. Lives in Toronto with her fiancé Stuart.

Where did you previously work?I was a postdoctoral fellow for three years in a developmental biology lab at the University Health Network. My project was aimed at generating hematopoietic stem cells from human embryonic stem cells.

What are your responsibilities as manager?The biggest part of my job is to provide education and training to graduate students and postdoctoral fellows on flow cytom-etry and how to operate flow cytometers. I provide users with assistance on how to set up experiments, prepare samples and suggest techniques to gather information on cells of interest.

I also coordinate the requests for proposals when we want new instruments and meet with vendors to discuss instrumentation. I spend a lot of time looking at the budget, figuring out what our costs are to run the facility, how much the facility makes, and how much we want to allocate for supplies, service contracts and repairs.

Has there been a learning curve?Yes. My previous work experiences were at the lab bench doing research. All of the administrative aspects are new. I also had to learn how to operate numerous cell sorters, and I’m learning to use advanced microscopes.

What drew you to SRI?I did my PhD here with Dr. Juan Carlos Zúñiga-Pflücker and it just felt like home. I like it because we have a lot of fantastic science going on here and I have a great rapport with many of the researchers.

How do you maintain a work-life balance?I love going out for dinner and to the movies. I didn’t get a lot of time to travel during my PhD, but I hope to do more travelling now. I’m getting married in June and would love to go to Italy, Spain or Hawaii on my honeymoon.

Behind the Scenes With Dr. Geneve Awong

6 • Sunnybrook Research Institute

Trainees’ Post: for Students and PostdocsWomen in science and the search for good mentorship

A year ago when Dr. Brandy Callahan was preparing her application for the L’Oréal Canada-UNESCO for Women in Science Awards, she never thought she would win. Then, Nov. 25, 2014, at a ceremony in Ottawa, Ontario, Callahan was presented with an Excellence in Research Fellowship, which gives Canadian women scientists the opportunity to pursue and expand their research projects.

“I was surprised to receive it. This award came at a good time because I was starting to feel a bit discouraged with my research and it was the ego-boost I needed,” says Callahan, a postdoctoral fellow supervised by Dr. Sandra Black, director of the Hurvitz Brain Sciences Research Program at Sunnybrook Research Institute (SRI). The award, worth a $20,000 stipend, will enable her to study further the role of cerebrovascular disease in the development of Alzheimer’s disease.

Trained as a clinical neuropsychologist at the Centre de recherche de l’Institut universitaire en santé mentale de Québec, Callahan came to work with Black to learn how to use neuro-imaging, a new area of focus in her research. “I’m learning how to use neuroimaging techniques that are specialized to detect white matter changes in the brain, which may give us some kind of hint as to whether someone is at a higher risk for developing dementia,” says Callahan.

Here, she talks to Eleni Kanavas about what it’s like to be a woman in science and why it matters to find good role models to stay motivated in the field.

Who inspired you to pursue a career in research?

I’ve been pretty lucky to have had consistently very good mentors, and some of them have been women, but most of them have been men. My thesis supervisor with whom I worked for six years was an excellent mentor. He encouraged me to explore my interests and curiosities. He was present and provided guidance, but he also let me explore new ideas on my own, which allowed me to discover my scientific identity.

Dr. Black is an amazing role model for women specifically because I think she is a phenomenal example of how productive and prolific someone can be while having a family, teaching and being a clinician. I feel she’s very involved and very good at everything. She’s really been an inspiration and a great mentor to me.

Why is it important for mentors to encourage young women to pursue science?

I think having role models in science can definitely encourage girls to think about careers that they might not have otherwise considered. Having female role models in science conveys the idea that there is a place for women in these kinds of jobs.

Are there certain characteristics that make a good mentor standout?

Someone who is able and willing to play two roles: the supervisor and someone who will listen and be receptive to your ideas.

How would you describe mentorship in the Black lab?

One thing I love about working in her group is that we do a lot of peer mentoring. She has other postdoctoral fellows and graduate students that work for her, and even though I’m not formally anybody’s supervisor, other students can come to me for questions or supervision. I often see the other postdocs and bounce ideas or questions off them.

What advice do you have for female trainees uncertain about a science career?

My first piece of advice is definitely to try it out because I’m so happy that I did. I was lucky to have a good supervisor and a good environment, but it ended up being so much more rewarding and fun than I expected.

The other piece of advice for women considering a career in science is to find a supervisor or a mentor that you love working with because grad school is long and difficult and science in general can be quite discouraging. But if you have someone there whom you can talk to and who will let you explore your own ideas and guide you, then it can be the most rewarding experience.

Dr. Brandy Callahan thanks her mentors for inspiring her passion for research. [Photo: Eleni Kanavas]

NEXUS SPRING 2015 • 7

ApplauseRecognizing the scientific and scholarly achievements of Sunnybrook Research Institute faculty and trainees

Dr. Mario Masellis, an associate scientist in the Hurvitz Brain Sciences Research Program, was recognized with a 2014 Maud Menten New Principal Investigator Prize as a finalist in clinical research from the Canadian Institutes of Health Research Institute of Genetics (CIHR-IG). The prize recognizes the excellence of Canadian new investigators working in health research within the CIHR-IG’s mandate.

Dr. Eranga Ukwatta, a postdoctoral fellow with Dr. Graham Wright, director of the Schulich Heart Research Program, received a postdoctoral fellowship from the Natural Sciences and Engineering Research Council of Canada to develop image-processing algorithms for cardiovas-cular imaging. He also won the First Prize Award at the 13th annual Imaging Network Ontario Symposium in London, Ontario.

Dr. Greg Stanisz, a senior scientist in Physical Sciences, was awarded the 2014 Edmond Odette Prize for innovation and technology in cancer care by Sunny-brook. The prize, worth $5,000, celebrates an individual within the Odette Cancer Program who has significantly contrib-uted to improving cancer care through developments in imaging, therapeutic or other technologies. Stanisz is developing a

unique magnetic resonance imaging pulse sequence that can be used to monitor a patient’s response to therapy.

Dr. Nick Daneman, a scientist in the Trau-ma, Emergency & Critical Care Research Program, was named a Phase 2 Clinician Scientist from the Canadian Institutes of Health Research. He will receive $180,000 over three years to conduct a randomized controlled trial that will compare the length of time necessary for effective antibiotic therapy to treat bloodstream infections.

Dr. Jon Barrett, director of the Women & Babies Research Program, was named the inaugural Waks Family Chair in Maternal-Fetal Medicine Research at Sunnybrook. The endowment will enable Barrett to focus on the clinical care of patients with high-risk pregnancies and births, and support research and education in this arena. The gift was established by a donation by Fred and Linda Waks,

matched by family and friends. Read the full story at sunnybrook.ca/research.

Dr. Soham Rej, a geriatric psychiatry fellow supervised by Dr. Nathan Her-rmann, an associate scientist in the Hurvitz Brain Sciences Research Program, was awarded a fellowship from the Canadian Institutes of Health Research. He will use the funds, $110,000 over two years, to study pharmacogenetic techniques to learn about which biological mechanisms underlie kidney disease in bipolar disorder.

Dr. Sean Udow, a clinical fellow supervised by Dr. Mario Masellis, an associate scien-tist in the Hurvitz Brain Sciences Research Program, was awarded a one-year clinical fellowship worth $50,000 from Parkinson Society Canada. His research will focus on dementia in patients with Parkinson’s disease and Lewy bodies, two neurode-generative diseases with similar clinical and pathological features. He aims to examine

the effect of blood pressure fluctuations on cerebral blood flow and cognition using clinical and neuroimaging parameters.

Dr. Kullervo Hynynen, director of Physi-cal Sciences, was chosen as the winner of the 2014 Rayleigh award by the Institute of Electrical and Electronics Engineers (IEEE). The Rayleigh award represents the IEEE’s highest honour for achievement within the field of ultrasonics and is presented annu-ally by the Ultrasonics, Ferroelectrics and Frequency Control Society.

What’s OnMay to AugustBiological Sciences Seminar for TraineesDates: May 20; June 10, 24; July 8, 22; and Aug. 19 Titles to be announcedNoon–1 p.m.SG 22

May 25 and July 2D+H SRI Summer Student Research Program Orientation8:30 a.m.–noonMcLaughlin Auditorium, EG 18

June 153rd Annual Schulich Innovation Research Day7:30 a.m.–4 p.m.McLaughlin Lecture Theatre, EG 61

June to August D+H SRI Summer Student Research Program SeminarsThursdays 2–3 p.m.SG 22

August 20D+H SRI Summer Student Research Program Poster Competition1–4:30 p.m.McLaughlin Auditorium, EG 18

Editor: Stephanie RobertsWriters: Eleni Kanavas, Stephanie Roberts and Betty Zou Nexus is published by the office of communications, Sunnybrook Research Institute: sunnybrook.ca/research. We welcome your suggestions. Please send them to Eleni Kanavas at eleni.kanavas@sri.utoronto.ca.

Dr. Trisha Roy, a surgical resident and PhD student supervised by Drs. Andrew Dueck and Graham Wright at Sunnybrook Research Institute (SRI), is using magnetic resonance imaging to study plaque composition in peripheral arterial disease. Read more about her work in the 2015 SRI Magazine on newsstands and online at sunnybrook.ca/research. [Photo: Nation Wong]