Personalized Medicine in the Genomics Era An International Symposium on Childhood Heart Disease Renaissance Hotel Downtown Toronto October 17–18, 2011

Labatt Family Heart Centre

www.heartcentrebiobank.ca/symposium

GenomeHeart Organizing Faculty Dear Participant It is with great pleasure that we introduce and welcome your participation in the SickKids Heart Centre Biobank and international GenomeHeart network hosted symposium, Personalized Medicine in the Genomics Era: An International Symposium on Childhood Heart Disease. This is an exciting new event highlighting state of the art approaches to personalized medicine for the child with heart disease. Experts in cardiology, developmental biology, pharmacology, genomics, bioinformatics, stem cell biology and ethics will present new approaches on how to apply emerging technologies to diagnostics and therapeutics for the child (and adult) with heart disease. The symposium is hosted by international experts belonging to a diverse group of medical and research specialists from across North America and Europe providing a unique opportunity to engage in a broader exchange of knowledge while networking and forming valuable working relationships. We have invited a world class faculty of scientists, physicians and applied professionals to participate in this exciting state of the art symposium. This symposium is funded by the Ontario Ministry of Research and Innovation International Strategic Opportunities Program, the Ontario Genomics Institute, MITACS and the SickKids Labatt Family Heart Centre and the SickKids Research Institute. The symposium sponsors are Cellular Dynamics as well as our gold sponsor Artificial Intelligence in Medicine. The symposium is a two day event. Day 1 will bring together international experts in the field of genomics, pharmacogenomics, bioinformatics, cardiology and clinical genetics to discuss current state of the art as well as future directions in the application of personalized medicine to childhood heart disease, and to address the gaps in knowledge that need to be addressed. This will have broad implications for the genomics applications towards the study of complex human disorders. Day 2 will bring together international experts in stem cells, tissue engineering, cardiac development and drug discovery to discuss the technology as well as strengths and limitations of stem cell platforms towards disease modeling, drug discovery and toxicology screens and their application towards personalized medicine. We look forward to your participation in this exciting event. Networking events are scheduled during the duration of the symposium which will be valuable to all attendees, faculty, and organizing committee. We hope to see you there! Sincerely, Program Organizing Faculty 2

Seema Mital, MD (Chair), The Hospital for Sick Children, Toronto Dr. Seema Mital currently leads several multicentre genomics initiatives including the SickKids Heart Centre Biobank (PI), Transplant Centre Biobank (PI), the GenomeHeart Network (PI) and the Pediatric Heart Network sharing the common goals of studying the genetic contribution to the etiology and outcomes of childhood heart disease. The Heart Centre Biobank serves as one of the largest resources of DNA and of somatic cells for reprogramming and disease modeling which supports several researchers including Dr. Mital’s interests in cardiac differentiation of pluripotent stem cells for disease modeling, drug discovery and cardiac biomarker discovery. Dr. Mital is currently Staff Cardiologist at SickKids Hospital and Associate Professor, Department of Pediatrics at the University of Toronto. James Ellis, PhD (Co-Chair), The Hospital for Sick Children, Toronto Dr. James Ellis is an expert in reprogramming somatic cells to induced Pluripotent Stem (iPS) cells to model human disease. His research is focused on modeling Rett Syndrome and other autism spectrum disorders, cystic fibrosis and cardiac disease using mouse and patient specific iPS cells. He is a Professor in the Department of Molecular Genetics at the University of Toronto, and a Senior Scientist at the Hospital for Sick Children. Michel Brudno, PhD, University of Toronto, Toronto Judith Goodship, MD, Institute of Human Genetics, Newcastle, UK Peter Gruber, MD, PhD, University of Utah, Salt Lake City, USA Bernard Keavney, MD, Institute of Human Genetics, Newcastle, UK Gordon Keller, PhD, McEwen Center of Regenerative Medicine, Toronto Antoon Moorman, MD, Amsterdam Medical Centre, Netherlands Barbara Mulder, MD, Amsterdam Medical Centre, Netherlands Alex Postma, PhD, Amsterdam Medical Centre, Netherlands Stephen Scherer, PhD, The Hospital for Sick Children, Toronto Mike Tyers, PhD, School of Biological Sciences, Edinburgh, UK

Keynote Speakers Kenneth Chien, MD, MGH Cardiovascular Research Center, USA Dr. Kenneth Chien is a renowned stem cell biologist specializing in cardiovascular research, as well as a pioneer in developing new therapeutic strategies to prevent the onset and progression of heart failure. Dr. Chien is currently Scientific Director of the Cardiovascular Research Center at Massachusetts General Hospital and Professor, Cell Biology at Harvard Medical School. He is a member of the Harvard Stem Cell Institute, where he leads the Universitywide Cardiovascular Stem Cell Biology Program.  3

Joseph Wu, MD, PhD, Cardiovascular Medicine, Stanford University, USA Dr. Wu is a renowned researcher in stem cell biology, gene therapy, genomics, and molecular imaging with current research on biological pathways in adult stem cells, embryonic stem cells, and induced pluripotent stem cells. Dr. Wu is currently an Associate Professor, Department of Medicine (Cardiology) and Department of Radiology at the Stanford School of Medicine.

Featured Speaker Matthew Hurles, PhD, Wellcome Trust Sanger Institute, UK Dr. Matthew Hurles has led major initiatives to characterize structural variation in the human genome, and integrate this knowledge into common disease, rare disorder and population genetic studies. Dr. Hurles currently has a leadership role in several large consortia, including the 1000 genomes project (www.1000genomes.org), the Deciphering Developmental Disorders initiative (www.ddduk.org ) and the UK10K project (www.uk10k.org ), and coordinates rare disease research at the Sanger Institute, within which he leads a programme of research on the genetic architecture of congenital heart disease.

Faculty Speakers

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Gregor Andelfinger, MD, PhD, Assistant Research Professor, Department of Pediatrics, University of Montreal Toshiyuki Araki, PhD, Assistant Scientist, Ontario Cancer Institute, Toronto Sarah Bowdin, MD, Staff Geneticist, Hospital for Sick Children, Toronto Michael Brudno, PhD, Associate Professor, Department of Computer Science, University of Toronto Derek Chiang, PhD, Assistant Professor, Department of Genetics, UNC School of Medicine, USA Kenneth R. Chien, MD, Director, MGH Cardiovascular Research Center, Boston, USA Niteesh Choudhry, MD, PhD, Assistant Professor, Harvard Medical School, Boston, USA John Coles, MD, Senior Associate Scientist, Physiology & Experimental Medicine, Hospital for Sick Children, Toronto Nicole Dubois, PhD, McEwen Center for Regenerative Medicine, Toronto James Ellis, PhD, Senior Scientist, Developmental & Stem Cell Biology, Hospital for Sick Children, Toronto Andrew Emili, PhD, Associate Professor, Proteomics & Bioinformatics, University of Toronto Klaus Fiebig, PhD, Chief Scientific Officer & VP, Research Programs, Ontario Genomics Institute, Toronto Kamal Garcha, PhD, Manager, Cell Reprogramming, Centre for Commercialization of Regenerative Medicine (CCRM), Toronto Judith Goodship, MD, Professor of Medical Genetics, Institute of Human Genetics, Newcastle, UK Anthony Gramolini, PhD, Associate Professor, Physiology, University of Toronto

Steven Greenway, MD, Cardiology Fellow, Hospital for Sick Children, Toronto Peter Gruber, MD, PhD, Associate Professor, Surgery, University of Utah, Salt Lake City, USA Matthew Hurles, PhD, Human Genetics, Wellcome Trust Sanger Institute, UK Samer Hussein, PhD, Samuel Lunenfeld Research Institute, Toronto Shinya Ito, MD, Professor, Medicine, Pharmacology, Department of Paediatrics, Hospital for Sick Children, Toronto Steven Kattman, PhD, Senior Scientist, Cellular Dynamics International, Wisconsin, USA Bernard Keavney, MD, Professor of Cardiology, Institute of Human Genetics, Newcastle, UK Bartha Knoppers, PhD, Director, Centre of Genomics and Policy, Montreal, Quebec Rebecca Laposa, PhD, Assistant Professor, Pharmacology and Toxicology, University of Toronto Peter Liu, MD, Senior Scientist, Division of Experimental Therapeutics, Toronto General Research Institute John MacEachern, President, Canadian Congenital Heart Alliance, Canada Freda Miller, PhD, Professor, Department of Molecular Genetics, University of Toronto Seema Mital, MD, Associate Professor of Pediatrics, Hospital for Sick Children, Toronto Robert Passier, PhD, Associate Professor, Leiden University Medical Centre, Netherlands Alex Postma, PhD, Assistant Professor, Anatomy, Embryology & Physiology, Amsterdam Medical Centre, Netherlands Michael Phillips, PhD, Scientific Director, Pharmacogenomics Centre, University of Montreal Milica Radisic, PhD, Associate Professor, Institute of Biomaterials and Biomedical Engineering, University of Toronto Andrew Redington, MD, Division Head Cardiology, Hospital for Sick Children, Toronto Stephen Scherer, PhD, FRSC, Director, The Centre for Applied Genomics, Hospital for Sick Children, Toronto William Stanford, PhD, Professor, Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa Mike Tyers, PhD, Professor of Systems Biology, School of Biological Sciences, Edinburgh, UK Joseph Wu, MD, PhD, Associate Professor, Cardiovascular Medicine, Stanford University, USA

Social Events: Faculty Dinner Senses Restaurant, 328 Wellington Street West, October 16, 2011 at 7:00 p.m. Dinner for all invited faculty is scheduled for Sunday October 16th at Senses Restaurant located at 328 Wellington Street West (attached to the SOHO Metropolitan Hotel which a 4 min walk from the Renaissance) Networking Reception Horizons at the CN Tower, 301 Front Street West, October 17, 2011 at 6:30 p.m. Included in the cost of registration is a reception which will be held at the event venue Horizons located at the Look Out Level within the CN tower. Horizons has dramatic sweeping views of Toronto and will host poster sessions as well as a cocktail and hors d’oeuvre reception for all attendees on the evening of Monday October 17th. The reception will provide an opportunity to network and interact over food and drinks. 

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Program

›  1:30-3:30  Cardiac Pharmacogenomics: Personalized Approaches Moderators: Peter Liu, Seema Mital

Monday October 17, 2011 ›  7:00  Breakfast and Registration

1:30

Cardiac Pharmacogenomics: An Overview Michael Phillips, Montreal University, Montreal, Canada

1:55

Pharmacogenetics: How Children Differ From Adults Shinya Ito, Hospital for Sick Children, Toronto

›  8:00-9:45  Opening Session: Genomics of Complex Disorders: New Approaches (1) 8:00

Welcome Remarks, Seema Mital (Chair)

8:10

Living with CHD: 70 Years and Running John MacEachern, Canadian Congenital Heart Alliance, Nova Scotia

2:20

Designing a Pharmacogenetic Drug Trial Seema Mital, Hospital for Sick Children, Toronto

8:30

Featured Research: Population variation and Exome Studies in Familial CHD Matthew Hurles, Wellcome Trust Sanger Institute, Cambridge, UK

2:45

Cost-effectiveness of Phamacogenetic Therapies Niteesh Choudhry, Harvard Medical School, Massachusetts, USA

9:00

GWAS in Congenital Heart Disease: New Insights Bernard Keavney, Institute of Human Genetics, Newcastle, UK

9:25

Copy Number Variation in CHD Steven Greenway, The Hospital for Sick Children, Toronto

›  3:15  Panel Discussion ›  3:30-4:00  Break ›  4:00-5:30  Designing Genomics Studies in CHD: Round Table Moderators: Bernard Keavney, Gregor Andelfinger

›  9:45-10:15  Break ›  4:00-4:30  Best Abstract Winners Presentations ›  10:15-12:15  Genomics of Complex Disorders: New Approaches (2) Moderators: Sarah Bowdin, Matthew Hurles 10:15 Next Generation Sequencing for Complex Disorders Stephen Scherer, The Hospital for Sick Children, Toronto 10:40 Algorithms for Characterizing Transcript Diversity with RNA-Sequencing Derek Chiang, UNC School of Medicine, North Carolina, USA 11:05 Bioinformatics for Next-Generation Sequencing Michael Brudno, University of Toronto, Toronto 11:30 From Biobanks to Stem Cells: New Challenges Bartha Knoppers, McGill University, Montreal, Canada 12:00 Panel Discussion ›  12:15-1:30  Lunch

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›  12:30-1:15 Lunch & Learn: Enhancing Biobanking and Collaborative Research with Web-based Systems Jack Golabeck, Artificial Intelligence in Medicine, Toronto

4:00

CNVs Contribute to Congenital Left-sided Heart Disease Marc-Phillip Hitz, Wellcome Trust Sanger Institute, UK

4:15

Global Rare Genic CNVs Contribute to Isolated CHD Rachel Soemedi, Institute of Human Genetics, Newcastle, UK

›  4:30-5:30  Round Table Discussion Defining CHD Subtypes: A Cardiologist’s Perspective, Andrew Redington, The Hospital for Sick Children, Toronto Defining CHD Subtypes: A Developmental Biologist’s Perspective, Alex Postma, Amsterdam Medical Center, Amsterdam, Netherlands Defining Population Controls for CHD, Matthew Hurles, Wellcome Trust Sanger Institute, Cambridge, UK Power for Genetic Studies in CHD, Judith Goodship, Amsterdam Medical Center, Amsterdam, Netherlands Funding Patient-Oriented Research in Genomic Medicine, Klaus Fiebig, Ontario Genomics Institute, Toronto ›  6:30-9:00 p.m.  Poster Session & Networking Reception Location: Horizons CN Tower, 301 Front Street West 7

Tuesday October 18, 2011 ›  8:00-10:15  Stem Cells for Cardiac Disease Modeling (1) Moderators: James Ellis, Freda Miller 8:00

Keynote: Clinical Hurdles of Pluripotent Stem Cell Therapy Joseph Wu, Stanford University, California, USA

8:45

Modeling Neurocardiac Syndromes: Rett, 22q11del, Williams James Ellis, The Hospital for Sick Children, Toronto

9:10

Modeling Rasopathies: Noonan, Leopard, Costello and CFC Toshiyuki Araki, Ontario Cancer Institute, Toronto

9:30

Keynote: Cardiovascular Regenerative Therapeutics via Paracrine Factor Modified RNA Kenneth Chien, MGH Cardiovascular Research Center, USA

›  10:15-10:45  Break ›  10:45-12:40  Stem Cells for Cardiac Disease Modeling (2) Moderators: Joseph Wu, John Coles 10:45 Modeling Cardiac Developmental Disorders Peter Gruber, University of Utah, USA 11:10 Genomic Instability in iPSCs Samer Hussein, Samuel Lunenfeld Research Institute, Toronto

›  1:30-1:45  Lunch & Learn: CCRM – a Capital-efficient, Collaborative Model of Regenerative Medicine Commercialization Kamal Garcha, Centre for Commercialization of Regenerative Medicine, Toronto ›  2:00-4:30  Personalized Stem Cells: Technology to Therapeutics Moderators: Andrew Emili, Mike Tyers 2:00

Proteomic Analysis of Human ES Derived Cardiac Cells for Cardiac Biomarker Discovery Anthony Gramolini, University of Toronto, Toronto

2:25

Bioinformatics for Biomedical Systems Mike Tyers, School of Biological Sciences, Edinburgh, UK

2:50

Stem Cells for Drug Discovery Robert Passier, Leiden University Medical School, Leiden, Netherlands

›  3:15-3:30 Break 3:30

PK Modeling: Drug Metabolism Using In Vitro Differentiated ES Cells Rebecca Laposa, University of Toronto, Toronto

3:55

Tissue Engineering and Biomaterials for Cardiovascular Regeneration Milica Radisic, University of Toronto, Toronto

›  4:20  Panel Discussion ›  4:30  Closing Remarks

11:30 Optimizing Cardiovascular Differentiation Strategies Nicole Dubois, McEwen Center for Regenerative Medicine, Toronto

Accepted Posters 11:50 Integrating iPSCs with Systems Genetics to Dissect Cardiovascular Disease Mechanisms William Stanford, University of Ottawa 12:15 Industrial Generation of Human iPSC-derived Cardiomyocytes for Modeling Cardiac Function and Disease Steven Kattman, Cellular Dynamics, Wisconsin, USA

The following abstracts have been accepted for presentation: Increased RNA Editing in Children with Cyanotic Congenital Heart Disease Sharon Borik, Gideon Paret, The Hospital for Sick Children, Toronto The role of serious congenital heart disease in the reproductive fitness of 22q11.2 deletion syndrome Gregory Costain, Anne Bassett, Centre for Addiction and Mental Health, Toronto

›  12:40-2:00  Lunch ›  1:00-1:30  Lunch & Learn: Creating and Operating a Biorepository Tanya Daljevic & Mina Safi, Hospital for Sick Children, Toronto 8

Assessing the impact of genetic variation in Islet-1 on congenital heart disease subtypes Roslyn Cheung, Seema Mital, The Hospital for Sick Children, Toronto

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Pediatric Participation in Research: Lessons Learnt from a Population-based Cardiac Biorepository Tanya Daljevic, Seema Mital, The Hospital for Sick Children, Toronto

MYBPC3 deletion increases risk for left ventricular dysfunction with coronary artery disease among South Indians Ashok Kumar Manickaraj, KumarasamyThangaraj, The Hospital for Sick Children, Toronto

Extracardiac Anomalies in Children with Congenital Heart Defects Fatima Fazalullasha, Seema Mital, The Hospital for Sick Children, Toronto

Smad3-dependent and -independent pathways are involved in peritoneal membrane injury Pranali Patel, Margetts PJ, McMaster University, Hamilton

MedSavant: a platform for identifying causal variants from disease sequencing studies Marc Fiume, Michael Brudno, University of Toronto

Exome sequencing to identify novel genetic variants associated with familial congenital heart disease Neetu Rakhra, Seema Mital, The Hospital for Sick Children, Toronto

Increasing Burden of Environmental Risk Factors for Congenital Heart Disease in the Current Era Alan Fung, Seema Mital, The Hospital for Sick Children, Toronto Copy number variants contribute to congenital left-sided heart disease Marc-Phillip Hitz, Gregor Andelfinger, The Wellcome Trust Sanger Institute, UK Induced pluripotent stem cells as a tool to model Williams-Beuren Syndrome Shahryar Khattak, James Ellis, The Hospital for Sick Children, Toronto Elastin regulates smooth muscle cell differentiation in human induced-pluripotent stem cells in Williams-Beuren syndrome Caroline Kinnear, Seema Mital, The Hospital for Sick Children, Toronto Patterning Human Embryonic Stem Cell-Derived Cardiomyocytes In A High-throughput Combinatorial Screen to Discover Protein Therapeutics for Myocardial Infarction Petra Luecker, Peter Zandstra, University of Toronto Senescence-mediated Fibrosis During Cardiac Differentiation: Aging Young Hearts Naila Mahmut, Seema Mital, The Hospital for Sick Children, Toronto Anthracycline induced cellular damage during human pluripotent stem cell cardiac differentiation Naila Mahmut, Seema Mital, The Hospital for Sick Children, Toronto Common genetic variations in drug biotransformation enzymes can affect the rate of metabolism of drugs and significantly influence drug levels and toxicity Katherine McLean, Seema Mital, The Hospital for Sick Children, Toronto Influence of CYP3A5 genotype on the pharmacokinetic profile of tacrolimus in paediatric transplant patients Katherine McLean, Seema Mital, The Hospital for Sick Children, Toronto

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Phenotypic specificity of 1q21.1 rearrangements and GJA5 duplications in 2437 congenital heart disease patients and 6760 healthy controls Rachel Soemedi, Bernard Keavney, Institute of Genetic Medicine, Newcastle University, UK Global rare genic copy number variants contribute to isolated sporadic congenital heart disease Rachel Soemedi, Bernard Keavney, Institute of Genetic Medicine, Newcastle University, UK Gene screening of the secondary heart field network in Tetralogy of Fallot patients Ana Topf, Judith Goodship, Institute of Genetic Medicine, Newcastle University, UK Use of human embryonic stem cell-derived cardiomyocytes as an in vitro model of human cardiovascular hypertrophy Sara Nunes, Milica Radisic, University of Toronto

Registration Registration is available online at: www.heartcentrebiobank.ca/symposium Online registration closes October 14, 2011 Registration after this date will be available onsite on October 17–18, 2011 Registration Fees GenomeHeart Members, Labatt Family Heart Centre Staff.............................................. $

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Trainees, Students, Allied Health Professionals ............................................................... $ 100 Physicians, Research Professionals, Others . .................................................................. $ 200 CME Credits This event is an Accredited Group Learning Activity as defined by the Maintenance of Certification Program of the Royal College of Physicians and Surgeons of Canada and approved by the Canadian Paediatric Society. This course is approved for 14 credit hours under the Maintenance of Certification (MOC) program of the Royal College of Physicians and Surgeons of Canada. 11

Program Organizers Seema Mital, MD Program Chair Associate Professor of Pediatrics The Hospital for Sick Children

James Ellis, PhD Co-Chair Senior Scientist The Hospital for Sick Children

Tanya Daljevic Program Coordinator Clinical Research Associate The Hospital for Sick Children

SOHO METROPOLITAN HOTEL ST.



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  Renaissance Toronto Downtown Hotel Symposium venue

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 SoHo Metropolitan Hotel Faculty dinner venue

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318 Wellington St. West (corner of Wellington and Blue Jays Way, Toronto) CN TOWER

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  Horizons Networking reception venue 301 Front Street West (located within the CN Tower)

RENAISSANCE HOTEL*

Symposium Sponsors This program is sponsored by the Ontario Ministry of Research and Innovation, Ontario Genomics Institute, MITACs organization, Labatt Family Heart Centre, SickKids Research Institute

This program is supported in name only by the American Heart Association’s Council on Cardiovascular Disease in the Young We thank our industry sponsors Artificial Intelligence in Medicine (Gold sponsor) Cellular Dynamics International