Cardiovascular Sciences Collaborative Program 16 … · CSCP Student Day 2015, Page 1 Cardiovascular Sciences Collaborative Program . 16. th. Annual Student Research Day . The 16th

CSCP Student Day 2015, Page 1

Cardiovascular Sciences Collaborative Program 16th Annual Student Research Day

The 16th Annual Cardiovascular Sciences Collaborative Program (CSCP) Student Research Day was held on Wednesday, April 8, 2015. Each year the Research Day provides trainees an opportunity to present their research to their peers in a welcoming environment promoting discussion and the free flow of ideas. The event provides a platform for expression of scientific ideas and inspiration for the mind, pushing the boundaries of current scientific paradigms in the field of cardiovascular research. This year, Dr. Carin Wittnich, Director of the CSCP, led the day with opening remarks highlighting the excellence and diversity of the CSCP. The morning continued with the students sharing their research aimed at improving the treatment and prevention of cardiovascular disease, followed by inspiring presentations from our guest speakers, Dr. Paul Dorian, Division of Cardiology & Clinical Pharmacology, and Dr. Carin Wittnich, Professor of Surgery & Physiology. Awards were presented to students receiving the “Bigelow Book Prize” and the “Lorne Phenix Graduate Award”. As well, certificates were handed out to students who had completed their CSCP training. The afternoon continued with more excellent student presentations concerning molecular mechanisms and imaging and analysis of cardiovascular disease. A workshop on preparing an academic CV was given by Dr. Wittnich. Awards were also presented to students who were judged to have given the best oral presentation and most innovative presentations.

~~~~~~~~~~~~~~~~~~~~ STUDENT PRESENTATIONS As part of the CSCP requirements, all students must present their research once during their graduate training. This presentation consists of a 10-minute talk followed by a 3-5 minute question period. This year students were grouped into three main topics – seen below – with excellent and innovative presentations given throughout. Session I: Molecular Mechanisms of Cardiovascular Disease (Chair: Mark Blaser) Hajera Amatullah, PhD/PSL Targeted Deletion of DJ-1 Attenuates Morbidity and Mortality in Experimental Sepsis Through Enhanced Bacterial Clearance


Robert Civitarese, MSc/IMS The Fibroblast-Specific α11β1 Integrin is Important for Post-Natal Cardiomyocyte Development and Function Danny D. Dinh, MSc/PSL Recovery of Skeletal Muscle Microvascular Myogenic Reactivity after Major Blockade Joobin Sattar, MSc/PSL Investigating the Mechanism & Functional Role of RGS5 Upregulation in VSMCs Following Statin Treatment Adil Rasheed, PhD/PHM Liver X Receptors (LXR) Modulate the Negative Effects on Endothelial Progenitor Cells after Feeding a High Cholesterol Diet Session I highlighted the importance of basic research and how understanding fundamental processes can drive the discovery of new treatment approaches. All five presentations demonstrated how a specific protein can influence physiological and pathophysiological responses and provided novel insights into disease mechanisms and potential therapeutic targets.

Session II: Imaging and Analysis of Cardiovascular Disease (Chair: Amish Jain) Tina Binesh Marvasti, MSc/IMS Haptoglobin 2-2 Genotype is Associated With Presence and Progression of MRI Depicted Carotid Intraplaque Hemorrhage Navneet Singh, PhD/IMS Carotid Intraplaque Hemorrhage and Cardiovascular End-Organ Outcomes: Preliminary Core Site Results Travis Wilder, MSc/IMS Determining the Trends in Right Ventricular Dysfunction and Tricuspid Regurgitation after Single Ventricle Palliation for Neonates with Hypoplastic Left Heart Syndrome and Their Differential Impact on Survival Omodele Olowoyeye, PhD/IMS Developing a Novel MR Technique for Measuring Flow Mediated Dilation In session II the speakers introduced new approaches to image and analyze cardiovascular disease. The first presentation focused on identifying a biomarker that can be used for the identification of pre-symptomatic individuals at a high risk of developing intraplaque

(Session I: L-R): Mark Blaser, Robert Civitarese, Adil Rasheed, Danny Dinh, Joobin Sattar, Hajera Amatullah


hemorrhage, while two subsequent presentations from the same lab focused on magnetic resonance imaging; with one assessing the ability of magnetic resonance imaging depicted intraplaque hemorrhage to predict cardiovascular outcomes. Another presentation in this session centered on using echocardiographic data to analyze the outcomes of children with congenital heart disease.

Session III: Modeling and Applications of Molecular Mechanisms in Cardiovascular Disease (Chair: Arash Ghashghai) Zachary Laksman, MSc/IMS Modeling Human Atrial Fibrillation Using Pluripotent Stem Cells Farrokh Mansouri, PhD/IBBME Model of Electrophysiology and Metabolism of the Heart Ji Dong K. Bai, MSc/IMS Identification and Mechanistic Studies of Novel Gluconeogenesis Regulators for Anti-Diabetic Drug Repurposing Using Transgenic Zebrafish Pck1 Reporters Azza Ramadan, PhD/IMS Effects of Long Term Autophagy Inhibition with Chloroquine on the Development and Progression of Experimental Abdominal Aortic Aneurysms

High fidelity, consistent models are important tools for studying cardiovascular disease. Session III presentations featured an in vitro model of atrial fibrillation generated from human embryonic stem cells able to display appropriate electrophysiological responses and an in silico model of the heart that incorporates electrophysiology and metabolism to faithfully predict NADH dynamics. Both models have potential to be used in drug development: for drug screening or studying drug mechanisms of action.

Two other presentations investigated drug candidates to treat cardiovascular disease. One presenter was able to identify four compounds from an FDA-approved clinical drug library able to down-regulate PEPCK expression that could potentially have an anti-diabetic effect. Another presenter studied whether chloroquine could be used to treat abdominal aortic aneurysms and found that it would not be an effective treatment when administered in a global and non-specific manner.

(Session II: L-R): Amish Jain, Omodele Olowoyeye, Tina Binesh Marvasti, Travis Wilder, Navneet Singh


Session IV: Cardiovascular Health and Clinical Implications (Chair: Cedric Manlhiot) Danielle C. Bentley, PhD/EXS Characterization of Post-Exercise Hemodynamics Following Two Handgrip Protocols in a Cohort of Older Women Shira Sasson, MSc/PCL Implications of Acute Exercise-Induced Pulmonary Hypertension on the Right Heart in Endurance Athletes Rawan Rumman, MSc/IMS Disease Beyond the Arch: A Systematic Review of Middle Aortic Syndrome in Childhood Julieta Lazarte, MSc/IMS Human Leukocyte Antigen-G Polymorphisms as Predictors of Early Cardiac Allograft Vasculopathy Adam McKillop, PhD/IMS Rehabilitative Exercise and Activity Clinical Trial in Congenital Heart Disease (REACT IN CHD)

Accurate definition and stratification of disease is important to good patient care. In the final Session of the day, one researcher investigated pulmonary pressures in performance athletes during exercise and identified “high” and “low” pressure generator groups with distinct heart function characteristics and troubling similarities in the right heart between “high” pressure generators and early-stage pulmonary hypertension patients. Another investigator conducted a systematic review of scientific journal articles of Middle Aortic Syndrome and identified a gap in understanding the etiology of the disease with 64% of cases being idiopathic and identified rates of involvement for various extra-aortic arteries with the renal artery being the most common. One speaker presented their work on the association between HLA-G single nucleotide polymorphisms and early cardiac allograft vasculopathy (CAV) having discovered that the +3196 CC/CG genotype is associated with reduced risk for early CAV while the +3196 GG genotype is associated with increased risk.

While improvements in treatment are vital, ideally cardiovascular disease can be prevented in the first place by promoting cardiovascular health. One presenter investigated the ability of a commercially available ZONA handgrip device as well as an in-house device as exercise tools to reduce the systolic blood pressure and increase the heart rate of normotensive, post-menopausal women, but found that these were not effective in the tested cohort. The final presentation described efforts in applying Motivational Interviewing as a means to increase

(Session III: L-R): Arash Ghashghai, Zachary Laksman, Azza Ramadan, Ji Dong K. Bai, Farrokh Mansouri


physical activity among adolescents with Congenital Heart Disease. While efficacy results are still under study, the presentation highlighted the difficulties in patient recruitment and adherence in clinical studies, especially when targeting a young population.

SESSION PRESENTATION AWARD WINNERS Each presenter was evaluated for the best oral presentation and most innovative research by members of the organizing committee. Criteria, which was objectively scored, included content (quality of research, research knowledge), visuals (clarity, readability), delivery (voice level, pacing), translational potential of research, data interpretation and analysis (research techniques), ability to answer questions and overall impression. Certificates and gifts were presented to the winners by a member of the Organizing Committee, Alan Lam. Congratulations to Adil Rasheed (Session I) for “Best Oral Presentation” for his insightful and well-delivered presentation on the liver X receptors and how they modulate the negative effects of cholesterol on endothelial progenitor cells. Adil was able persuade the audience with his findings and addressed all questions thoughtfully and convincingly.

(Session IV: L-R): Adam McKillop, Cedric Manlhiot, Julieta Lazarte, Danielle Bentley, Rawan Rumman

(L-R): Alan Lam, Adil Rasheed


Congratulations to awardee Zachary Laksman (Session III) for “Most Innovative Research” for his novel approach of using pluripotent stem cells to model human atrial fibrillation in vitro.

~~~~~~~~~~~~~~~~~~~~ GUEST SPEAKERS The CSCP would like to thank our guest speakers, Drs. Dorian and Wittnich, for their very insightful and interesting talks that related to their careers and how they got to where they are today!! Both speakers initiated an animated discussion with the audience and answered questions in a thought provoking and helpful manner. These talks are a great way for students to hear and gain insights from individuals they aspire to become, and we certainly are grateful for the excellent talks provided!

Dr. Paul Dorian is the Dexter H.C. Man Chair in Cardiology, Department Director, Division of Cardiology, University of Toronto and Staff Cardiac Electrophysiologist at St. Michael's Hospital. He is Professor of Medicine in the Division of Cardiology and in the Division of Clinical Pharmacology at the University of Toronto, and a Staff Scientist at the Li Ka Shing Knowledge Institute.

(L-R): Dr. Carin Wittnich, Dr. Paul Dorian, Katherine Allan

(L-R) Alan Lam, Zachary Laksman


Dr. Dorian received his medical degree from McGill University in Montreal in 1976. He continued training in Internal Medicine and Cardiology at the University of Toronto, and received certification by the Royal College of Physicians and Surgeons of Canada in Internal Medicine in 1983 and certification in Cardiology in 1984. He completed training in Clinical Pharmacology at the University of Toronto in 1982, and received an MSc in Pharmacology from the University of Toronto in 1982. From 1983 to 1985, he completed a Fellowship in Cardiac Electrophysiology at Stanford University Medical Centre in California. He is the immediate Past-President of the Canadian Heart Rhythm Society, Chairman of the Cardiac Arrest Committee, St. Michael’s Hospital, Co-PI on the NIH funded Resuscitation Outcomes Consortium, serves on the steering committee of multiple multicenter clinical trials in arrhythmia care, and is the Chair of the Canadian Cardiovascular Society Quality Committee. His research interests include basic science research in advanced cardiac life support and atrial fibrillation, the clinical pharmacology of antiarrhythmic drugs, and clinical research on implanted devices, antiarrhythmic drugs, and quality of life in patients with arrhythmias. He has published over 350 peer reviewed papers and is Associate Editor of the textbook Electrophysiological Disorders of the Heart.

~~~~~~~~~~~~~~~~~~~~ Dr. Carin Wittnich is a tenured Full Professor in the Departments of Surgery and Physiology at the University of Toronto, and is the founding Director of the Cardiovascular Sciences Collaborative Program. As well, she is Staff in the Division of Cardiac Surgery at The Hospital for Sick Children and Division of Cardiology at the Toronto General Hospital. She has held grants from the Heart & Stroke Foundation and MRC for work in newborn hearts response to stress and role of sex. As primary supervisor, she has trained over 13 MSc and 5 PhD students to date and continues to maintain an active research program, having published over 80 papers in peer reviewed journals. Outside of the University, she is a founding Director and Senior Scientist of the Oceanographic Environmental Research Society, serves on a number of editorial boards for scientific journals and is Editor-in-Chief of the Journal of Marine Animals and Their Ecology (JMATE). Dr. Wittnich was recognized by the Department of Surgery in 1991 with the George Armstrong Peters Prize for her outstanding initial research productivity and then in 1999 with the Lister Prize for her continuing Heart & Stroke Foundation of Ontario grant funded research of international stature. In 1996 the University of Toronto awarded her the prestigious “Northrop Frye Award” for her innovation and exemplary linking of teaching and research. The Faculty of Medicine continues to recognize her outstanding teaching contributions with the “Sustained Excellence in Graduate Teaching Award” (2005), Excellence in Life Science Teaching (2008) and Excellence in Laboratory Undergraduate Teaching (2013). Outside the University of Toronto, in 2001 she was invested with the Order of Ontario for her work in promoting awareness and education of heart disease in women and children, and received the Queen's Jubilee Medals (Golden 2002, Diamond 2012). In 2006, she received the OVC Distinguished Alumni Award from her alma mater the University of Guelph for her outstanding contributions and successes in both academic and research fields. Her volunteer efforts are also well known and respected and she received the OVMA Recognition Award for her work with Hurricane Katrina relief efforts.

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(L-R): Adrienne Siu, Dr. Wittnich, and Kathryn Lipsett, Dr. Wittnich

CERTIFICATES/AWARDS Dr. Wittnich presented certificates to students who successfully completed the Cardiovascular Sciences Collaborative Program over the past year: MSc Carlos S. Fernando, IMS (Supervisor: G. Moe) Kathryn R. Lipsett, PSL (Supervisor: A. Gramolini) Zhen Q. Lu, PSL (Supervisor: A. Gramolini) Nour Qa’aty, IMS (Supervisor: A. Hinek) Adrienne G. Siu, MBP (Supervisor: G. Wright) Lily Zou, PCL (Supervisor: P. Dorian)

PhD Gabriela Lima de Melo Ghisi, EXS (Supervisor: S. Thomas) June Guo, PSL (Supervisor: A. Giacca) Congratulations to all the students and success in their future career endeavours! Continuing the spirit of success and achievement, Dr. Wittnich continued with the annual CSCP student awards and presented:

~~~~~~~~~~~~~~~~~~~~ 2015 Bigelow Book Prize Recipient – Navneet Singh The CSCP congratulates Navneet Singh (shown here with Dr. Wittnich), a doctoral candidate in the Institute of Medical Science, supervised by Dr. A. Moody, who was presented with the 2015 Bigelow Book Prize for his continued and sustained academic scientific excellence. Identifying patients most at risk for strokes and heart attacks is a challenge for physicians. Advancements in Medical Imaging provide a major opportunity to directly visualize arteries implicated in strokes and heart


attacks, allowing for the detection of diseased vessels that may benefit from treatment. Dr. Navneet Singh, an aspiring Radiologist Physician-Scientist, is dedicated to the translation of advanced and novel imaging technologies from bench to bedside, and hopes to provide physicians with cutting-edge tools to help patients. His Ph.D. thesis is focused on evaluating intraplaque hemorrhage, a component of unstable atherosclerotic plaque that can be visualized with MRI and predicts strokes and heart attacks. His CIHR supported Ph.D. aims to investigate MRI detected intraplaque hemorrhage, using a multicenter Canadian Atherosclerosis Imaging Network trial, under the mentorship of Dr. Alan R. Moody. 2014-15 Lorne Phenix Graduate Award Recipient – Antoinette Bugyei-Twum

The CSCP congratulates Antoinette Bugyei-Twum (shown here – middle), a doctoral candidate in the Institute of Medical Science, supervised by Dr. K. Connelly, who was presented with the 2014-15 Lorne Phenix Graduate Award for her continued and sustained academic scientific excellence. Shown here with Antoinette is Ms. Kathryn Phenix and Dr. Wittnich. Investigating the Role of TGF-β Signaling in the Failing Diabetic Heart Heart failure constitutes a significant health care

burden. In Canada, over 500,000 individuals are reported to experience heart failure. Of these individuals, roughly 50% experience a specific type of heart failure called heart failure with preserved ejection fraction, a condition characterized at the cellular level by cardiomyocyte hypertrophy and fibrosis. Strikingly, individuals with diabetes are particularly prone to developing heart failure with preserved ejection fraction. However, with considerable debate surrounding the exact nature/cause of cardiac dysfunction attributable to diabetes, very little advancement has been made with respect to the development of effective therapies. In fact, a major challenge to the development of effective therapies is the identification of modifiable pathways responsible for the hypertrophic growth of cardiomyocytes – a key pathological feature of the failing diabetic heart. Of the reported pathways, the transforming growth factor beta 1 (TGF-β1) signaling pathway emerges as an attractive therapeutic target as it is consistently implicated in organ hypertrophy and fibrosis. With a large proportion of diabetic women at an increased risk of developing cardiovascular complications, the aim of my research is to better understand the role/contributions of TGF-β1 in diabetes-induced cardiac dysfunction – an aim that closely aligns with the spirit of the Lorne Phenix Graduate Award. Following the awards presentations, students socialized and networked during the complimentary lunch.

~~~~~~~~~~~~~~~~~~~~ ACADEMIC CV WORKSHOP This year Dr. Wittnich provided her ever popular academic workshop on CV preparation to the students. She went over the key ingredients to a succinct yet impactful CV and identified some common errors and oversights made by students as they look to the future and begin putting


together their own CV. Key points included the importance of a targeted CV, honesty in the information contained and clarity so that the reader can appreciate the breadth and depth of the individual. Dr. Wittnich’s presentation was well received and tailored specifically to CSCP students.

~~~~~~~~~~~~~~~~~~~~ CLOSING The Student Research Day was a success and would not have been possible without the combined efforts of several individuals. Thank you to the Organizing Committee, Antoinette Bugyei-Twum (Chair), Alan Lam (Committee member) and Katherine Alan (Committee member) for all their hard work; Victoria Simpson for her support and knowledge in making this day successful, Professors Dorian and Wittnich for their outstanding and inspiring presentations, and the Sessions Chairs, Mark Blaser, Amish Jain, Arash Ghashghai and Cedric Manlhiot for keeping the sessions running smoothly.

We are also grateful to the generous donation from GoodLife Fitness, the University of Toronto Book Store, the Phenix family, the Bigelow family, and the contributions from our participating units.

Thank you to all the CSCP students and to all involved in making the 16th Annual CSCP Student Research Day a great success!

(L-R): Katherine Allan, Antoinette Bugyei-Twum, Alan Lam

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Cardiovascular Sciences Collaborative Program 16 … · CSCP Student Day 2015, Page 1 Cardiovascular Sciences Collaborative Program . 16. th. Annual Student Research Day . The 16th