Monthly Archives: August 2015

Dr. Bobby Yanagawa

yanagawa-photo I was very fortunate to receive PSI grants as a resident working in the laboratory of Subodh Verma at St. Michael’s Hospital. At the time, we proposed to look at the role of a novel tumor suppressor gene in cardiac remodeling. It was an ambitious project that unfortunately turned into a dead end. This is the unavoidable reality of life science research and one must remain ready to fail and pick oneself up again, ready for the next challenge. A quick change of direction was needed so we switched gears and turned our attention to study the role of a key microRNA as an important upstream regulator of bone morphogenetic protein-2, a central biological checkpoint in aortic stenosis (Yanagawa B et al. J Thorac Cardiovasc Surg 2012;144:256-62). We also described the human fingerprint of autophagy activation pathways in ischemia and reperfusion injury in human heart samples (Krishna KK, Yanagawa B, et al, J Thorac Cardiovasc Surg 2014;147:1065).

I am currently completing a surgical fellowship at the Division of Cardiothoracic Surgery at Mt. Sinai Hospital in New York and will re-join the Division of Cardiac Surgery this year as a Surgeon-Scientist and Assistant Professor. We will pick up where we left off to interrogate human tissues to shed much needed light on the pathogenesis of common human valvular heart diseases. We are focusing on congenital bicuspid and calcific aortic stenosis as well as degenerative and rheumatic mitral valvulopathy, diseases for which the only definitive treatment is surgical.

The Canadian cardiovascular community is very fortunate to have strong national funding agencies such as Canadian Institutes of Health Research and the Heart and Stroke Foundation. However, there is a gap in funding for smaller initiatives and innovative projects spearheaded by medical residents and young investigators that don’t quite encompass the depth and breadth of a full grant. I believe that PSI facilitates the coming together of such innovative research teams to perform outside-the-box research and to generate enough data to then move on to full grant funding. For our team and indeed for my career, PSI has provided much needed support that we used as a catapult to move into exciting new directions. It is a jewel for young investigators in Ontario and I hope that they continue to embrace and support young scientists.

Bobby Yanagawa completed a PhD at the University of British Columbia, MD at the University of Toronto as well as Post-Doctoral Fellowships at the University of Wales College of Medicine (Cardiff, UK), National Cardiovascular Center (Osaka, Japan) and St. Michael’s Hospital (Toronto, Canada). He is currently a Clinical Instructor at Mt Sinai Hospital (NYC, New York) and will be joining the staff at St. Michael’s Hospital in July 2015. His clinical focus is minimally-invasive valve surgery and off-pump surgical revascularization. His research interests are the pathogenesis of valvulopathy and arrhythmias. He has contributed to the publication of over 40 original research articles, 13 reviews and 9 book chapters in such journals as Nature Medicine, Nature Communications, Lancet Diabetes and Endocrinology, Journal of Biological Chemistry, Circulation Research and Journal of Thoracic and Cardiovascular Surgery.

Dr. Charles Tator

tator-photo
Dr. Charles Tator

A concussion research centre was started at the Toronto Western Hospital in 2010 which we called the Canadian Sports Concussion Project. This project involved many clinician-scientists and basic scientists working in a large number of fields in clinical and basic neuroscience including neurosurgery, neurology, neuroradiology, neuropsychology, neuropathology, and others. The first funding agency we approached was PSI, and we were very fortunate in obtaining funds. The funds were specifically focused on examining the effects of multiple concussions in retired CFL football players. We used a multi-pronged approach including neurological examination, neuropsychological assessment, imaging with MR, and examination of players’ brains that were willed to the Centre by their families.

Over the years we have made many discoveries including the fact that chronic traumatic encephalopathy, a specific neurodegenerative disease, is present in some, but not all, of the players who sustained multiple concussions during their playing careers. We also discovered that we can detect changes in a particular white matter tract in the brain of these players called the uncinate fasciculus which connects the frontal and temporal lobes. We have been able to relate the damage to this tract to the neuropsychological tests showing impulsivity. In my view, it is an incredible accomplishment to have come this far so quickly, and a significant amount of the credit for this goes to PSI for funding this type of physician sponsored patient-oriented research.

Thank you PSI!

Dr. Tator is a practicing neurosurgeon and neuroscientist with research projects in the concussion spectrum of disorders in patients. He also does research at the basic science level on the pathophysiology and treatment of spinal cord injury. He sees patients in the Division of Neurosurgery offices at the Toronto Western Hospital, and his basic science laboratory is in the Krembil Discovery Tower at the Toronto Western Hospital. He is a graduate of the University of Toronto Medical School and the University of Toronto Neurosurgery Resident Training Program, and have practiced in his professional life in University of Toronto hospitals. During his training, he also trained in research and received MA and PhD degrees.

Dr. Stephen Freedman

freedman-photoDr. Stephen Freedman
My PSI Story

Shortly after relocating from Chicago to Toronto to take a new faculty position at The Hospital for Sick Children, I submitted a grant to PSI entitled “Emergency Department Rapid Intravenous Rehydration for Pediatric Gastroenteritis: A Randomized Controlled Trial”. Luckily this was awarded funding from PSI ($156,000). This initial support allowed me to establish a research program at The Hospital for Sick Children with a focus on pediatric acute gastroenteritis – the most common reason children are brought to emergency departments for care. With research infrastructure in place I was able to complete a complex blinded clinical trial that was eventually published in BMJ in 2011. The success of this trial at an early stage of my career was instrumental to proving what could be achieved and how outcomes could be improved in children with acute gastroenteritis. We followed up this funding with a subsequent funding request for a study entitled “Isotonic versus hypotonic IV maintenance fluids in children: a randomized controlled trial”. The provision of funding to conduct this trial in 2010 has led to the completion of a 624 patient clinical trial that has the potential to further dramatically alter the management of children with gastroenteritis. The results of this study are currently being analyzed.
These early successes have led to my exploring larger avenues of research and have truly given me a leg up to achieve success. I currently am funded by the Bill & Melinda Gates Foundation, CIHR, the NIH and the Thrasher Research Fund. None of this would likely have been possible without the support from PSI early on in my academic career. I look forward to future collaboration with PSI and to seeing the results that their support will yield.

Dr. Freedman has been a member of the Sections of Pediatric Emergency Medicine and Gastroenterology at the Alberta Children’s Hospital in Calgary since 2012. He completed his residency at The Hospital for Sick Children (Toronto) in 2000 after completing medical school at McGill University. He then went to Chicago to complete a pediatric emergency medicine fellowship at Children’s Memorial Hospital while simultaneously obtaining a Master’s of Science in Clinical Investigation at Northwestern University.

His research focus has been on applying clinical research to the treatment of children with gastroenteritis and includes the use of antiemetics, probiotics, and rehydration. He is the principal investigator on multiple probiotic multicentre clinical trials with funding support from both CIHR and the NIH. Dr. Freedman leads an Alberta Innovates Health Solutions Team Collaborative Research Innovation Opportunity (CRIO) called APPETITE (Alberta Provincial Pediatric EnTeric Infection TEam). He is also conducting work in Pakistan with funding from The Bill and Melinda Gates and Thrasher Research Foundations. Together, his work in developing and developed nations is focused on improving outcomes in children with gastroenteritis.

The PSI ripple effect

kym-photo
By Dr. Kym Boycott
Children’s Hospital of Eastern Ontario (CHEO)

I first met Dr. Jodi Warman Chardon about four years ago when she attended one of my lectures in Neurogenetics. Jodi was a resident at the time and demonstrated a keen interest in neurogenetics research and the CHEO clinical care model. I knew intuitively that her enthusiasm coupled with her neurology background defined Jodi as a promising clinician scientist; and that she would bring a valued added skillset to our innovative rare disease research program.

The CARE for RARE research program that I co-lead from the Children’s Hospital of Eastern Ontario (CHEO) Research Institute has earned an international reputation for successfully diagnosing and developing treatments for rare diseases. Thousands of rare diseases have a neurological component, and yet there are only a few proven leaders in the field of neuromuscular neurogenetics. As such, Jodi’s neurology expertise would be an asset for our clinic too.

Jodi pursued combined neuromuscular and neurogenetics fellowships of which she successfully completed at McGill University and CHEO, with protected time for research. Together we brought pediatric and adult patients alike into research projects while upholding the highest ethical standards; and we caught the attention of PSI at the same time.

PSI played an invaluable role in bringing Jodi’s research program in inherited muscle diseases to life. In short, PSI helped to launch a promising young clinician scientist early in her career! The funding allowed Jodi to use next-generation exome sequencing with patients that have genetic neuromuscular disorders which led to several important research discoveries, including identifying a novel gene for Limb Girdle Muscular Dystrophy (LGMD). This gene had never been described in humans before, so we are very proud of Jodi’s accomplishment and subsequent manuscript in Clinical Genetics.

The LGMD gene discovery is a marquee research project for Jodi, which has been integrated into the neurogenetics program at CHEO today. As a result, we can provide patients and their families with access to innovative technology to provide an evidence-based diagnosis of this disease.

The ripple effect of PSI funding gives Jodi, and many others like her, a solid start; her success in gene discovery of rare neurogenetic disorders will continue to improve the lives of patients across Canada for years to follow.

Kym Boycott is a Medical Geneticist at the Children’s Hospital of Eastern Ontario (CHEO) and Clinician Scientist at the CHEO Research Institute. She is an Associate Professor and holds a Tier II Research Chair in Neurogenetics from the Faculty of Medicine at the University of Ottawa. She completed her PhD, MD and FRCPC training in Medical Genetics at the University of Calgary. Dr. Boycott’s research, bridging clinical medicine to basic research, is focused on elucidating the molecular pathogenesis of rare genetic diseases using next-generation sequencing approaches. She has been the recipient of the Canadian Institutes of Health Research Clinical Investigatorship Award from the Institute of Genetics, the SickKids Foundation Young Investigator Award and the Basil O’Connor March of Dimes Young Investigator Award. She was the Lead Investigator of the Genome Canada and CIHR funded ‘Finding of Rare Disease Genes in Canada’ (FORGE Canada) project, which investigated the molecular etiology of more than 250 rare pediatric diseases, identifying the cause in more than 55% and making 67 novel disease gene discoveries. She currently leads the Genome Canada and CIHR funded large-scale project ‘Enhanced CARE for RARE Genetic Diseases in Canada’, which is focused on improving the clinical care of patients and families by expanding and improving the diagnosis and treatment of rare diseases. Dr. Boycott moves the international rare disease agenda forward through her role as the Chair of the Diagnostics Committee of the International Rare Disease Research Consortium.