Dr. Kevin Katz

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I completed my training in infectious diseases and medical microbiology, as well as a Master’s degree in Laboratory Medicine and Pathobiology, at the University of Toronto in 2004. I developed a special interest in the epidemiology of antibiotic resistant organisms and infection prevention and control. A renewed focus on patient and occupational safety emerged as a result of the Toronto SARS epidemic, and created unique opportunities in community hospitals. I joined North York General Hospital as their medical Director of IPAC in 2004, aspiring to create an academic program with the potential to impact more broadly. After all, by some measures, 80% of all care is delivered in community hospitals.

Over the last decade there has been a major shift in the epidemiology of Methicillin Resistant Staphylococcus aureus, with the emergence of new MRSA strains that transmit in community settings (schools/daycare, jails, gyms, homeless shelters, etc.). I was lucky enough to be granted PSI funding for a project to assess the risk of Methicillin Resistant Staphylococcus aureus in household settings and to compare this risk based on strain type (community MRSA strain versus healthcare MRSA strain). This led to a successful multi-site study which demonstrated, contrary to common belief, that both CA- and HA-MRSA strains transmit equally well in the household setting. This study was the foundation for numerous other projects and publications focussing on various facets of the emergence of community-associated MRSA strains, including defining at-risk groups, outbreak investigations, delineating the most appropriate laboratory screening technique to detect colonization, and conducting point prevalence studies of CA-MRSA in purulent skin and soft tissue infections presenting to emergency departments across Canada.

The Physician Services Incorporated Foundation has given me opportunities that other granting agencies could not. PSI’s emphasis on ‘health research that is relevant to patient care’ and a preference for new investigator proposals make PSI Foundation a unique gem. The PSI Foundation is also unique in its willingness to fund research by community physicians in community settings. I am very thankful to PSI Foundation for getting my academic career off the ground, and positioning me for success.

Dr. Kevin Katz is the Medical Director of Infection Prevention and Control at North York General Hospital. He is a Medical Microbiologist and Infectious Diseases specialist and an Associate Professor in the Department of Laboratory Medicine and Pathobiology at the University of Toronto. He has special research interests in healthcare-acquired infections and multidrug resistant organisms.

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Dr. Graham JW King

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Elbow dislocations are the second most common dislocation in adults. These dislocations are often associated with fractures, which have a great influence on elbow stability and patient outcomes. Excessive joint laxity and re-dislocation are frequently encountered due to the loss of these secondary osseous constraints. Prolonged immobilization may reduce the incidence of late instability; however, permanent stiffness is the usual consequence. As a result, stiffness and later arthritic changes are common sequelae of elbow dislocations both with and without associated fractures. Furthermore elbow fractures are second in frequency only to the wrist. With the advancing age of our population the incidence of these fractures has been rising rapidly and are becoming a significant financial burden for the health care system. Despite advances in our understanding the biomechanics of the elbow and in the diagnosis and treatment of its disorders, there are many questions that have yet to be resolved and their management remains unsatisfactory.

The Roth McFarlane Hand and Upper Limb Centre Bioengineering Laboratory has been advancing our understanding of elbow biomechanics over the last twenty years. Located in the Lawson Research Health Institute at St. Joseph’s Health Centre in London, this laboratory is a major hub of biomechanics research in the Departments of Surgery and Mechanical Engineering at Western University. A variety of projects are conducted by a team comprised of engineering and medical trainees, residents and fellows. This research encompasses the application of engineering-based studies to address clinical problems such as fracture fixation, soft-tissue and ligament repair, and implant replacement. These studies range from the employment of basic bench-top approaches to the use of advanced state of the art testing systems and simulators that permit the experimental-based reproduction of joint function. In addition, implant development is a major thrust of this research; more recently with the development and testing of reverse-engineered patient-specific implants. In collaboration with industrial partners, new implant systems have been developed and these are now commercially available. Also, improved surgical and rehabilitation techniques, that have been evaluated in the laboratory, have been implemented clinically. More recently, intra-operative measurement and guidance systems have been developed as components of computer-assisted surgery.

As part of our research program we have been interested in developing the next generation of clinician-scientists. In partnership with the Physicians Services Incorporated we have received funding for four resident research projects over the last eight years. These types of grants are not currently not provided by CIHR or NSERC. Three of these projects are now complete and each of the residents who were awarded these grants have published their work and obtained Masters Degrees. Two are now working in academic medical centres while the third is completing advanced fellowship training.

In 2007 we were awarded a Resident Grant entitled “The Development and Application of a Forearm Testing Apparatus”. This novel device has allowed us to gain a better understanding of the role of the interosseous membrane in forearm stability and its relationship to radial head excision and replacement. This knowledge will assist surgeons in deciding the optimal diameter and thickness of radial head prostheses, the commonest joint replacement of the elbow. Furthermore the role of the interosseous membrane in load transfer and the effect of radial head excision and replacement provides a rationale for optimal patient care. In addition to presentations at a number of national and international meetings, three papers have been published, in part, as a result of this grant support.

  1. Lanting BA, Ferreira LM, Johnson JA, Athwal GS, King GJ. The effect of excision of the radial head and metallic radial head replacement on the tension in the interosseous membrane. Bone Joint J. 95-B:1383-7, 2013. PubMed PMID: 24078536.
  2. Lanting BA, Ferreira LM, Johnson JA, King GJ, Athwal GS. The Effect of Radial Head Implant Length on Radiocapitellar Articular Properties and Load Transfer within the Forearm. J Orthop Trauma. 28(6):348-53, 2014. PubMed PMID: 24088774.
  3. Lanting BA, Ferreira LM, Johnson JA, King GJ, Athwal GS. Radial head implant diameter: A biomechanical assessment of the forgotten dimension. Clin Biomech (Bristol, Avon). 2015 Mar 16. pii: S0268-0033(15)00077-7. doi: 10.1016/j.clinbiomech.2015.03.012. [Epub ahead of print] PubMed PMID: 25800117.

In 2010 we received a resident research grant entitled “Coronoid Fracture Repair and Reconstruction of the Elbow”. This study evaluated optimal techniques in coronoid fracture repair and reconstruction. The development of a coronoid prosthesis is a major advance of this research which was in part supported by the PSI. This has already been implanted in a patient as a custom device and we hope that this will be commercialized to provide a solution to a very challenging clinical problem, coronoid process insufficiency. We also validated the concept of transfer of the coronoid process as an autogenous solution to lesser magnitudes of coronoid deficiency. In addition to presentations at a number of national and international meetings, four papers have been published, in part, as a result of this grant support. Publication is pending for two additional papers.

  1. Alolabi B, Gray A, Ferreira LM, Johnson JA, Athwal GS, King GJ. Reconstruction of the coronoid using an extended prosthesis: an in vitro biomechanical study. J Shoulder Elbow Surg 21:969-76, 2012. PubMed PMID: 21782472.
  2. Alolabi B, Gray A, Ferreira LM, Johnson JA, Athwal GS, King GJ. Rehabilitation of the Medial- and Lateral Collateral Ligament-deficient Elbow: An In Vitro Biomechanical Study. J Hand Ther. 25:363-73, 2012. PubMed PMID: 22959533.
  3. Gray AB, Alolabi B, Ferreira LM, Athwal GS, King GJ, Johnson JA. The Effect of a Coronoid Prosthesis on Restoring Stability to the Coronoid-Deficient Elbow: A Biomechanical Study. J Hand Surg 38A1753-1761, 2013. PubMed PMID: 23830677.
  4. Alolabi B, Gray A, Ferreira LM, Johnson JA, Athwal GS, King GJ. Reconstruction of the coronoid process using the tip of the ipsilateral olecranon. J Bone Joint Surg 96A:590-6, 2014. PubMed PMID: 24695926.

In 2011 we received a resident research entitled “Distal Humeral Hemiarthroplasty of the Elbow”. This study was focussed on optimizing the design of distal humeral hemiarthroplasty, a developing option for the management of fragility fractures of the distal humerus. We were able to demonstrate some of the current challenges with distal humeral hemiarthroplasty including implant sizing, materials and the potential for cartilage wear due to altered joint contact. While further research is needed and remains ongoing, this novel project has advanced our understanding of hemiarthroplasty of the elbow and has the potential to influence hemiarthroplasty designs of other joints. Two papers have been published and publication is pending for one additional paper.

  1. Desai SJ, Deluce S, Johnson JA, Ferreira LM, Leclerc AE, Athwal GS, King GJ. An anthropometric study of the distal humerus. J Shoulder Elbow Surg. 23:463-9, 2014. PubMed PMID: 24560468.
  2. Desai SJ, Athwal GS, Ferreira LM, Lalone EA, Johnson JA, King GJ. Hemiarthroplasty of the elbow: the effect of implant size on kinematics and stability. J Shoulder Elbow Surg. 23(7):946-54, 2014.PubMed PMID: 24766788.

In 2014 we received a resident research grant entitled “Rehabilitation of the Ligament Deficient Elbow: A Biomechanical Study”. This study is ongoing is focussing on improving rehabilitation techniques for unstable fractures and dislocation. In addition providing an evidence based rationale for physiotherapists to provide safe and effective exercise programs, we are also evaluating the effectiveness of bracing which are often prescribed for these injuries.

In summary the resident research support provided by PSI is a novel granting program which in spite of the relatively small financial commitment is leading to significant advances in patient care. By encouraging residents in their training to gain skills in grant applications and translational research I expect this will encourage the physicians of tomorrow to remain engaged in research during their future careers which should improve the health of Ontarians.

Dr. Graham JW King received his MD degree at the University of British Columbia. After completing a rotating internship at the University of Alberta he went to the University of Toronto to train in orthopaedic surgery. During a research year in Toronto he became interested in orthopaedic biomechanics and soft tissue healing. After qualifying as an orthopaedic surgeon in 1989 he completed a clinical fellowship in hand and wrist surgery and a Master’s of Science degree at the University of Calgary. He then travelled to the Mayo Clinic to gain further clinical experience in wrist and elbow surgery and additional research experience in upper extremity bioengineering. In 1992 he joined the Department of Surgery at the University of Western Ontario. He established the Bioengineering Laboratory at the Hand and Upper Limb Centre at St. Joseph’s Health Centre. With his collaborators, Drs. David Chess, Louis Ferreira and James Johnson they have developed linkages with the Departments of Medical Biophysics, Mechanical Engineering and Biomedical Engineering. Over the past 20 years the laboratory has been successful in attracting extensive peer review funding including CIHR, CAS, CAN and NSERC and has numerous industry collaborations. His current research interests focus on the biomechanics of the wrist and elbow as well as computer and image guided surgery. He has received the Premier’s Research Excellence Award from the Government of Ontario and the J. Edouard Samson Research Award from the Canadian Orthopaedic Research Society. He has represented the Canadian Orthopaedic Association as a North American Travelling Fellow and an American, British and Canadian Travelling Fellow. He has also served as the president of the Canadian Orthopaedic Research Society. He is currently a Professor in the Department of Surgery at Western University and the Chief of Surgery at St. Joseph’s Health Centre. Dr. King was awarded a 2010 Dean’s Award of Excellence for his contributions to the Schulich School of Medicine and Dentistry.

Ingrid Tein MD

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I am extremely grateful to the PSI Foundation for its generous and critical support of our research endeavours in metabolic myopathies with a primary focus on fatty acid oxidation (FAO) disorders. This seminal support has furnished the basis for a number of clinical and basic research projects, the development of novel therapeutic interventions and a series of educational initiatives over the years.

Clinical relevance of fatty acid oxidation disorders

The metabolism of fatty acids (fatty acid oxidation) provides energy (ATP) for all high energy-dependent tissues such as muscle, heart, kidney, bowel, sperm, etc. The partial oxidation of fatty acids to ketones by the liver provides the brain with a critical alternative source of energy during times of hypoglycemia. The early recognition of fatty acid oxidation (FAO) disorders is very important for both pediatricians and child neurologists as they present with a spectrum of clinical disorders including progressive limb girdle lipid storage myopathy, recurrent episodes of life-threatening muscle breakdown (myoglobinuria), neuropathy, pigmentary retinopathy with night blindness, progressive cardiomyopathy, recurrent episodes of hypoglycemic hypoketotic coma or Reye-like syndrome, seizures, and mental retardation. They constitute a critical group of diseases because they are potentially rapidly fatal and a source of major morbidity. There is frequently a family history of sudden infant death syndrome (SIDS) in siblings. Early recognition and prompt institution of therapy and appropriate preventative measures, and in certain cases specific therapy, may be life saving and may significantly decrease long-term morbidity, particularly with respect to neurological sequelae, thereby significantly improving the quality of life for the child and their family. All currently known conditions are inherited as autosomal-recessive traits. There are now at least 25 known enzymes and specific transport proteins in the pathway of ß-oxidation and 18 have been associated with human disease. The most common defect is medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, which is one of the milder disorders, and which may have an incidence as high as 1 in 5000 live births. In the case of MCAD deficiency, if triggers for metabolic crisis such as fasting, prolonged exercise, shivering and stress are avoided and if there is rapid acute treatment of hypoglycemia with intravenous glucose infusion such as during infections with vomiting, the affected children should have an excellent outcome with a normal lifespan. Tissue dysfunction in FAO disorders arises from insufficient energy (ATP) production, deficient ketone body production by the liver, lipid storage in tissues and the toxicity of excessive metabolites that accumulate proximal to the metabolic block. The identification of abnormal serum acylcarnitines by electrospray ionization-tandem mass spectrometry of dried blood spots on filter paper in newborn screening programs has significantly enhanced the early recognition of these disorders which has allowed earlier intervention with an improvement in clinical outcome.

Results of our PSI supported research projects in fatty acid oxidation

Through PSI support, we have investigated the mechanisms of disease pathogenesis at a clinical, biochemical and molecular level through the intensive study of specific FAO disorders in vivo (in patients) and in vitro (in cell models) in order to provide insight into the precise correlation between genotype and phenotype and to provide key information regarding the protein and molecular basis of both normal and abnormal fatty acid oxidation. Using a translational bench-to-bedside approach, we have identified novel phenotypes and genotypes.

Carnitine palmitoyltransferase II (CPT II) deficiency

We identified carnitine palmitoyltransferase II (CPT II) deficiency, which is the most common cause overall of recurrent myoglobinuria (muscle breakdown) in males and females and in adults and in children, as a new cause for recurrent pancreatitis (Tein et al 1994). Furthermore on intensive clinical, biochemical and genetic study of a family pedigree with CPT II deficiency due to the common mutation (p.Ser113Leu), we demonstrated interesting clinical and biochemical heterogeneity in which the affected girl, who was homozygous for the mutation, had an unexpectedly high residual activity and her carrier brothers (who were heterozygous for the mutation) had lower than expected residual activities with unexpected clinical symptoms (Rafay et al 2005). This suggested that there were genetic, environmental and sex hormonal factors that influenced the biochemical and clinical presentations and highlighted the potential vulnerability of carriers if exposed to adequate FAO stressors, which was important for the counseling of the family.

Short-chain acyl-CoA dehydrogenase (SCAD) deficiency

In short-chain acyl-CoA dehydrogenase (SCAD) deficiency, we described a new clinical phenotype with progressive external ophthalmoplegia (limitation of eye movements) and multicore myopathy with severe contractures and early wheelchair dependence (Tein et al 1999). Based on the additional features of cataracts and cardiomyopathy, we investigated this young girl for evidence of elevated markers of free radical toxicity which we demonstrated in her blood. Based on this finding, we instituted a prospective treatment trial with antioxidant therapy which increased the power in her shoulder girdle muscles by six-fold, markedly improving her functional abilities in the upper extremities. Through our international network of colleagues, we then identified a series of children with the same mutation (c.319C>T) in the SCAD gene and identified common features of myopathy (30 % with multicore changes), developmental delay and the classic biomarkers but also found a wide clinical variability (Tein et al 2008). Of note, all patients were of Ashkenazi origin. Given the wide clinical variability, we concluded that this particular mutation could lead to wide clinical and biochemical phenotypic variability, suggesting a complex multifactorial/polygenic condition. Furthermore, we proposed that SCAD deficiency should be screened for in individuals with multicore myopathy, particularly among the Ashkenazim, given the potential for improvement or reversal of the muscle weakness with antioxidant therapy, particularly if instituted early before the development of severe muscle wasting and joint contractures. We then developed a cell model from the cultured skin fibroblasts of children with SCAD deficiency and with long-chain FAO defects such as CPT II and long-chain L-3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency in which we exposed the cells to an agent that enhanced free radical production. In order to simulate the typical stressors that lead to FAO crisis in affected children, we then exposed the cells to both hypoglycemia (as seen with fasting and vomiting) and hyperthermia (as seen with fever which is a stressor and also predisposes to the misfolding of certain proteins such as SCAD). We were able to demonstrate the extreme vulnerability of the SCAD and CPT II and LCHAD deficient cell lines to very early demise in culture, in sharp contrast to normal control cells and MCAD deficient cells which survived for significantly longer time periods. We were then able to increase cell survival in our SCAD and CPT II and LCHAD deficient cell lines by two- to seven-fold using specific antioxidants and an agent that increases the biogenesis of mitochondria (Zolkipli et al 2011). These remarkable results in cell culture will now form the basis for future clinical trials in children with these disorders.

Long-chain L-3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency

In LCHAD deficiency, we identified a new clinical phenotype with recurrent myoglobinuria and progressive neuropathy due to a novel genetic mutation (Ibdah et al 1998). Based on our careful clinical evaluation of our index case with this novel presentation and the apparent fragility of his muscle membranes to very minor walking exertion with release of muscle CK into the bloodstream, signifying muscle breakdown, and based on our knowledge of the membrane toxicity of long-chain fatty acids, we instituted a trial of oral prednisone. Prior to the prednisone the affected patient had marked limb girdle weakness and was almost wheelchair dependent. Following prednisone therapy, he had full restoration of muscle power to normal strength which was maintained on very low dose prednisone into adulthood (Tein et al 1995). His further course was complicated by progressive neuropathy leading to foot drop and marked weakness of the hands with a claw hand deformity whereby he could no longer write more than two lines at a time before fatigue. Again, based on emerging information regarding the importance of omega-3 very long-chain fatty acids (DHA) in nerve, mitochondrial and retinal membranes and the potential for deficiency in LCHAD deficiency, we supplemented our index case with a source of DHA which served to regenerate the peripheral nerves in his upper extremities leading to fully restored power of his hands and led to the reappearance of his formerly absent nerve conductions in the lower extremities which were also maintained on continuing DHA therapy (Tein et al 1999).

Carnitine/organic cation transporter family

In another project related to the clinical role of carnitine deficiency in male infertility, given that the highest concentrations of carnitine in the human body are found in spermatozoa and epididymal fluid (2000 X the serum carnitine concentrations), we demonstrated the different patterns of expression of the organic cation/carnitine transporter family (OCTN1, OCTN2 and OCTN3) in human sperm underlining the importance of carnitine transport and potentially reversible causes and treatment targets for male infertility (Xuan et al. 2003) as demonstrated in the mouse model of OCTN2 deficiency in which the associated male infertility is reversed with high dose L-carnitine therapy.

Knowledge Translation and Dissemination

In 1991, I founded and continue to direct the Neurometabolic Clinic, Neuroinvestigational Unit and Neurometabolic Research Laboratory at the Hospital for Sick Children, University of Toronto for the priorized clinical, biochemical and molecular investigation of children with metabolic myopathies and FAO disorders. We receive referrals from throughout Canada, the US, Caribbean, Europe, Middle East, Asia and South America. With the above investigations and PSI support, we have been able to expand the clinical phenotypes and genotypes, develop new diagnostic screening tests, and provide insight into the pathophysiological mechanisms of disease which has formed the basis for the development of new translational therapies aimed at bypassing or correcting the specific metabolic block, which have decreased long-term morbidity and mortality in affected individuals and have been successfully implemented internationally.

In 2010, the groundwork from our studies served as the basis for our formation of an International Metabolic Myopathies Focus Group which hosted over 150 international participants at the XIth International Child Neurology Congress in Cairo, May 2010. At each of the International Child Neurology Congresses in 2006, 2010, 2012, and 2014, we have organized a series of Neurometabolic Plenary Symposia as well as day-long Neurometabolic Satellite Symposia for the education of child neurologists, scientists, fellows, residents and nurses in different neurometabolic disorders including FAO disorders and metabolic myopathies with updates on new treatment strategies and novel pathophysiologic mechanisms. Given the participation by international colleagues, this has served to promote widespread dissemination of knowledge of the clinical recognition, diagnostic approach and treatment intervention as well as genetic counseling in these disorders.

PSI support has directly contributed to our publication of over 31 peer-reviewed articles in high impact journals such as Neurology, the Journal of Clinical Investigation and PLoS One and chapters in state-of-the-art Textbooks of Neurology such as Pediatric Neurology (Edited by Swaiman, Ashwal and Ferriero) and the Handbook of Clinical Neurology. The further impact of our clinical and basic research findings has elicited over 144 invitations for talks on Fatty Acid Oxidation Disorders and Metabolic Myopathies, 68 of which I have given as plenary talks at international congresses. This has included four Keynote Lectures at the Annual Scientific Congress of the Hong Kong Society of Child Neurology and Developmental Pediatrics, Nov. 2007; Presidential Symposium of the 10th Asian and Oceanian Congress of Child Neurology in Daegu, Korea June 2009; the Annual Garrod Association Congress, St. John’s Nfld, June 2010; the 2nd International Saudi Pediatric Neurology Congress, Nov. 2010. This work, in which PSI Foundation support was so critical, has also been honoured through my receipt of international awards (John Stobo Prichard Young Investigator Award, 8th International Congress of Child Neurology, Ljubljana, Slovenia. Sept. 1998; John H. Menkes Award, UCLA, Los Angeles, California, March 2012; Colleen Giblin Award Memorial Lectureship. Columbia University, NY, NY. May 2013).

Finally and very importantly, the funding from the PSI Foundation has enabled me to facilitate and nurture the training and development of a series of neurology residents, post-doctoral fellows and research trainees both locally and internationally who will serve as the next generation of clinician-scientists in this field.

Ingrid Tein BSc, MD, FRPC(C)
Director, Neurometabolic Clinic and Research Laboratory
Staff Neurologist, Division of Neurology
Associate Professor of Pediatrics, Laboratory Medicine and Pathobiology
Senior Associate Scientist, Genetics and Genome Biology Program, The Research Institute
The Hospital for Sick Children, University of Toronto
President, The International Child Neurology Association

Dr. Ingrid Tein obtained her BSc, MD, Pediatric fellowship and Pediatric Neurology fellowship at the University of Toronto. She completed her post-doctoral research in fatty acid oxidation disorders at Hopital Necker-Enfants Malades, University of Paris with Prof. Jean-Marie Saudubray and Prof. Jean Aicardi and in the Dept of Neurology, Columbia University, New York, NY with Dr. Darryl De Vivo and Dr. Salvatore DiMauro. Dr. Tein is Associate Professor of Pediatrics and of Laboratory Medicine and Pathobiology at the University of Toronto and founder and Director of the Neurometabolic Clinic, Investigational Unit and Neurometabolic Research Laboratory and Staff Neurologist in the Division of Neurology at the Hospital for Sick Children in Toronto. She is also a Senior Associate Scientist in the Genetics and Genomic Biology Program in the Research Institute of the Hospital for Sick Children. Dr. Tein currently serves as the President of the International Child Neurology Association (2014-18).

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

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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

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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.