Collaboration & Supported Studies

The Heart Centre Biobank Registry has formed collaborative partnerships across the province of Ontario to build and expand on its recruitment base to create a truly population-based registry. Collaborations have also been formed internationally.All collaborative centres and principal investigators are listed below:

Principal Investigators from Provincial Expansion Sites:

The Hospital for Sick Children
Principal Investigator: Dr.Seema Mital, MD

London Health Sciences Centre (Paediatric Site)
Principal Investigator: Dr. Luis Altamirano, MD

London Health Sciences Centre (Adult Site)
Principal Investigator: Dr. Lynn Bergin, MD

Hamilton Health Sciences Centre (Paediatric Site)
Principal Investigator: Dr. Tapas Mondal, MD 

Hamilton Health Sciences Centre (Adult Site)
Principal Investigator: Dr. Elaine Gordon, MD

Children’s Hospital of Eastern Ontario
Principal Investigator: Dr. Jane Lougheed, MD 

Kingston General Hospital
Principal Investigator: Dr. John Smythe, MD

Toronto General Hospital
Principal Investigator: Dr. Erwin Oechslin, MD

Mount Sinai Hospital
Principal Investigator: Dr. David Chitayat, MD

Human iPS Stem Cell Consortium:  

Stem cell technology brings great promise for the future of research.  In 2007 scientists discovered that you can take an individual’s skin cells, reprogram them into stem cells (iPS cells) and then change them into virtually any cell type in the body.  These cells can be used for disease modeling, drug screening for toxicity and new drug development, as well as for rejection-free transplantation in the future. The Heart Centre Biobank holds the largest skin cell bank in congenital heart disease worldwide!  The creation of a research sharing network between the world’s top leading stem cell scientists will help facilitate this science and lead to quicker discoveries.  The Heart Centre Biobank along with the Ontario human iPS cell facility has partnered with the Gladstone Institute of Cardiovascular disease in California, USA as well as Kyoto University, Kyoto, Japan through the Ontario Personalized Human Stem Cell Initiative.  Together this collaboration allows for the open sharing of resources and knowledge with the common goal of transforming the field of medicine.  

                         Supported Studies

The Heart Centre Biobank is currently supporting many institutional, national and international studies. Overall, these studies will achieve several goals. They will lead to the identification of genetic and environmental causes of heart defects in children and adults and help in predicting outcomes so treatment can be customized to individual patients. Studies of stem cell regulation in cardiac malformations will further our understanding of the biologic basis of disease and lead to the development of regenerative therapies. Partnership with industry will lead to the development of new genetic screening tests for individuals at risk for heart disease. Collaborations with leading experts in cell biology will lead to the discovery and development of newer and safer drugs for treatment of patients with heart defects. Some ongoing studies are listed below.



Genomic Variation in Human Cardiac Malformations
Seema Mital (PI), SickKids; Sarah Bowdin, Andrew Paterson, David Chitayat
This study will identify the genetic etiology of cardiac malformations.

Genetic Determinants of Right Ventricular Remodeling in Tetralogy of Fallot (TOF)
Seema Mital (PI), SickKids; Luc Mertens (PI), SickKids; Andrew Redington, Brian McCrindle, Shi Joon Yoo
This study will identify the genetic variations that contribute to right ventricular remodelling and dysfunction in patients after surgical repair of TOF patients.

Cardiac Stem Cell Regulation in Congenital Heart Disease
John Coles (PI), SickKids
This study will identify the role of Integrin-linked kinase in hypertrophy signaling and stem cell regulation in patients with TOF and dilated cardiomyopathy.

Developmental Basis of Cardiac Malformations
Seema Mital (PI), SickKids; David Chitayat (PI), Patrick Shannon
This study will identify the pathways of cardiac growth during fetal life in patients with cardiac malformations.

Genomic Basis of Cardiac Malformations
Seema Mital (PI), SickKids; James Ellis, Gordon Keller
This study will develop pluripotent models of cardiovascular disease and study the effect of gene defects and environmental exposures on cardiac differentiation.

Analzying the Molecular Basis of Hypertrophic Cardiomyopathy
Benjamin Neel (PI), University Health Network
This study will use human stem cells and differentiate them into heart cells to investigate the normal cardiac development.

The Role of microRNA in Vascular Remodeling
Deepak Srivastava (PI), Gladstone Institute
This study seeks to view the expression of miRNA in pulmonary vein stenosis and reversing this stenosis from occuring.

Induced Pluripotent Stem Cells for Cardiovascular Research
Benoit Bruneau (PI), Gladstone Institute
This study grows cardiomyocytes from skin cells to study genetically defined heart disease in effort to better understand these disease processes

High-throughput Sequencing to Identify Disease Causing Variants in Congenital Heart Disease
Seema Mital (PI), SickKids
To utilize novel and advanced technology to perform whole exome sequencing in children with familial CHD to identify gene defects or mutations that cause CHD and to expand this knowledge in the future to develop a genetic test that can be used for clinical screening in patients with CHD.

Clinical Assesment of Thrombosis in Children after Heart Surgery (CATCH Study)
Brian McCrindle (PI), SickKids
Thrombosis and hemorrhage are two important complications for children born with congenital heart disease. Little is known on how individual genetic variations influence these processes. We wish to evaluate the association between genes and risk, response and resolution associated with thrombosis after cardiac surgery.  These findings will help lead to a personalized approach to individualizing risk for treatment of thrombosis.  

Biomarkers of Heart Failure in Adults with CHD: Towards Personalized Medicine
Peter Liu (PI), University Health Network
The goal of this project is to discover biomarkers, which can help diagnose cardiac dysfunction or heart failure in this unique complex and growing population. The biomarker candidates may also provide insight into the unique pathways that lead to heart failure in this patient population, and offer more personalized approach to diagnosis and therapy.

Novel approaches to the prediction, diagnosis and treatment of cardiac late effects in survivors of childhood cancer
Paul Nathan (PI), Luc Mertens (PI), Seema Mital (PI, Genetics Core); SickKids
To identify genetic predictors of susceptibility to anthracycline and radiation-induced cardiac toxicity. Synthesis of imaging, biomarker and genetic findings will allow for the identification of those at greatest risk for developing clinically significant cardiac toxicity as a consequence of their cancer therapy. These at-risk individuals will be the focus of pilot intervention studies with the goal of preventing or mitigating the progression of cardiac toxicity.

Exome sequencing to identify mutations in a cohort of patients with CMP and right-sided structural heart defects
Sarah Bowdin (PI), SickKids
This study plans to look at the genetic information of individuals with cardiomyopathies and right-sided structural heart defects. This study will increase the understanding of why some children and adult have a greater risk for cardiomyopathy then others.  

Biologic Determinants of Right Ventricular Remodeling in Tetralogy of Fallot

Seema Mital (PI), SickKids
Despite surgical repair, patients with tetralogy of Fallot develop progressive leaking of the pulmonary valve with development of right ventricular dilation and dysfunction. The genetic cause of this is not known. This study will identify the genes that contribute to progressive RV dysfunction after surgical repair of TOF. The findings will help with the early identification of individuals at risk for RV problems later in life so that interventions can be done sooner.

Patterns and clinical significance of electro-mechanical dyssynchrony in pediatric dilated cardiomyopathy
Mark Friedberg (PI), SickKids
The goal of this study is to address the current deficits in our knowledge and understanding of electro-mechanical dyssyncynchrony in childhood DCM so that it may be possible if some children have the electrical and mechanical substrate for resynchronization and therefore benefit from new therapies.

Regulatory Map of the Human Cardiac Genome
Michael Wilson (PI), SickKids
The goal of this study is to enhance our knowledge of the regions of the human genome that function to regulate the genes essential for healthy cardiac function.

Regulatory Variants in Thrombosis
Michael Wilson (PI), SickKids
Identifying pathological alterations in human regulatory DNA will lead to new diagnostic tools for pediatric diseases and address outstanding questions in human gene regulation and epigenetics.

Genetics and Pharmacogenetics of systemic hypertension after transplantation
Seema Mital (PI), SickKids
This study will analyze genetic factors that influence the response to anti-hypertensive medications after cardiac transplantation.

Impact of Pathophysiology on Clinical Outcome in Patients with Congenital Heart Disease who Undergo Cardiac Surgery
John Coles (PI), SickKids
The aim of the study is to investigate pathophysiology as well as surgical outcome to gain a greater understanding of the the mechanism of congenital heart diseases.

Genomic Variations in Childhood Onset Heart Disorders
Gordon Keller (PI), Peter Liu (PI), Seema Mital (Co-Inv), University Health Network, SickKids


Genome-wide Association Study of Congenital Heart Disease
Bernard Keavney (PI), Judith Goodship (Co-Inv), Heather Cordell (Co-Inv), Newcastle, UK
This international project which look into a large number of individuals with congenital heart disease and look throughout the human genome for common variation that may be associated with risk of CHD.  The goal is to discover factors that predispose families to a risk of CHD with hopes of in the future identifying new preventive measures.  

Genetic causes of Congenital Heart Disease
Matthew Hurles (PI), Wellcome Trust Institute, UK
While Down syndrome accounts for roughly 50% of cases of AVSD, the genetic basis of non-Downs AVSD is not known. DNA from these patients will be sequenced to identify gene defects using advanced sequencing techniques. This knowledge will be useful in genetic and reproductive counseling in the long term and in better understanding of the pathways that cause CHD.