Inherited HeartDiseases

Research Areas

• Genetics of Dilated Cardiomyopathy
• Genetics of Atrial Fibrillation
• Zebrafish heart disease models

Research Overview 

Research work undertaken in the Sr Bernice Research Program in Inherited Heart Diseases focusses on two of the most common types of heart problems: dilated cardiomyopathy and atrial fibrillation. Inherited gene variants are being increasingly recognised as important causes of heart disease, but very little is known about what these genetic factors are and how they affect heart function. Led by Prof Diane Fatkin, her team of researchers is trying to find the faulty genes that cause inherited forms of dilated cardiomyopathy and atrial fibrillation. They are also trying to discover how these gene changes affect the heart’s contraction and rhythm. The researchers are using cutting-edge technology, including next-generation sequencing techniques, to find genetic variants in families with these disorders. To understand the molecular defects underpinning disease, the team is using a number of cell-based and animal models, including zebrafish. The overall objective is to define the genetic causes of dilated cardiomyopathy and atrial fibrillation and to translate this understanding to new approaches to diagnosis, treatment and prevention.

There are 3 key projects underway in the Inherited Diseases Laboratory, led by Professor Diane Fatkin;

1. Genetics of dilated cardiomyopathy and atrial fibrillation

The aim of this project is to identify disease-causing rare variants in families in which these disorders appear as a heritable trait. The team is exploring whole-genome sequencing and novel bioinformatics tools to discover gene mutations.

2. Zebrafish models of adult-onset heart disease

The team is developing new zebrafish models using genetic engineering technologies such as TALENs and CRISPR/cas9 as well as new techniques to study heart function. The group is one of the first in the world to use high frequency echocardiography to study heart size and contraction in adult zebrafish. The team is also adapting other techniques that are commonly used to assess human heart function, including electrocardiography (ECG) and stress testing.

3. Genes and environment

A combination of clinical studies in families and intervention studies in zebrafish models is being used to look at interactions between genetic susceptibility and environmental factors.

Lab Members

Renee Johnson, Clinical Research Coordinator

Celine Santiago, Postdoctoral Scientist

Renee Chand, Research Assistant

Jasmina Cvetkovska, Research Assistant

Monique Ohanian, Research Assistant

Magdalena Soka, Research Assistant

Gunjan Zhao, Research Assistant

Collaborators

Nikki Bart, Victor Chang Cardiac Research Institute

Charles Cox, Victor Chang Cardiac Research Institute

Michael Feneley, Victor Chang Cardiac Research Institute

Eleni Giannoulatou, Victor Chang Cardiac Research Institute

Robert Graham, Victor Chang Cardiac Research Institute

Richard Harvey, Victor Chang Cardiac Research Institute

Christopher Hayward, Victor Chang Cardiac Research Institute

Adam Hill, Victor Chang Cardiac Research Institute

Andrew Jabbour, Victor Chang Cardiac Research Institute

Anne Keogh, St Vincent's Hospital, Sydney

Jason Kovacic, Victor Chang Cardiac Research Institute

Peter Macdonald, Victor Chang Cardiac Research Institute

Boris Martinac, Victor Chang Cardiac Research Institute

Kavitha Muthiah, St Vincent's Hospital, Sydney

Jamie Vandenberg, Victor Chang Cardiac Research Institute

Emily Wong, Victor Chang Cardiac Research Institute

Richard Bagnall, Centenary Institute, Sydney

Robert Bryson-Richardson, Monash University, Melbourne

Tanya Hall, Hearts4heart

Jodie Ingles, Garvan Institute, Sydney

Paul James, Royal Melbourne Hospital, Melbourne

Jon Kalman, Royal Melbourne Hospital, Melbourne

Peter Kistler, Alfred Hospital, Melbourne

Andre La Gerche, Baker Heart and Diabetes Institute, Melbourne

Ilias Goranitis, University of Melbourne, Melbourne

Paul Lacaze, Monash University, Melbourne

Peter Molenaar, University of Queensland, Brisbane

Emily Oates, UNSW Sydney, Sydney

Nathan Palpant, University of Queensland, Brisbane

Mark Perrin, Royal Melbourne Hospital, Melbourne

Katrina Scurrah, University of Melbourne, Melbourne

Chris Semsarian, Centenary Institute, Sydney

Dominica Zentner, Royal Melbourne Hospital, Melbourne

International

Euan Ashley & Victoria Parikh, Stanford University, Stanford, USA

Roberto Barriales-Villa, Universidade da Coruña, A Coruña, Spain

Zofia Bilińska, National Institute of Cardiology, Warsaw, Poland

Rolf Bodmer & Karen Ocorr, Sanford Burnham Prebys Medical Discovery Institute

Alex Hoerby Christensen, Copenhagen University Hospital, Copenhagen, Denmark

Guido Claessen, KU Leuven, Leuven, Belgium

Perry Elliott, Barts Heart Centre, London, UK

Patrick Ellinor & Steven Lubitz, Massachusetts General Hospital, Boston, USA

Siv Fokstuen, University Hospitals of Geneva, Geneva, Switzerland

Pablo Garcia-Pavia, Hospital Puerta de Hierro, Madrid, Spain

Cynthia James & Anne Murphy, Johns Hopkins University, Baltimore, USA

Neal Lakdawala, Brigham and Womens' Hospital, Boston, USA

Dana Leifer, Weill Cornell Medicine, New York, USA

Wolfgang Linke, University of Munster, Munster, Germany

Elizabeth McNally, Northwestern University, Chicago, USA

Benjamin Meder, University of Heidelberg, Heidelberg, Germany

Marco Merlo & Gianfranco Sinagra, Cardiothoracic Department, ASUIT, Trieste, Italy

Luisa Mestroni & Matthew Taylor, University of Colorado, Aurora, USA

Jens Mogensen, Aalborg University Hospital, Aalberg, Denmark

Steven Niederer, King's College London, UK

Christine & Jon Seidman, Harvard Medical School, Boston, USA

James Ware, Imperial College, London, UK

Hugh Watkins, University of Oxford, Oxford, UK

1. Fatkin D, Calkins H, Elliott P, James CA, Peters S, Kovacic JC. Contemporary and future approaches to precision medicine in inherited cardiomyopathies. JACC Focus Seminar 3/5. J Am Coll Cardiol 2021;77:2551-2572.
2. Giudicessi JR*, Ackerman MJ*, Fatkin D*, Kovacic JC. Precision medicine approaches to cardiac arrhythmias. JACC Focus Seminar 4/5. J Am Coll Cardiol 2021;77:2573-2591. (*Co-first authors)
3. Taliun D,Fatkin D. Abecasis GR. Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program. Nature 2021;590:290-299.
4. Akhtar MM, Lorenzini M, Cicerchia M, Ochoa JP, Hey TM, Molina MS, Restrepo-Cordoba MA, Dal Ferro M, Stolfo D, Johnson R, Larranaga-Moreira JM, Robles-Mezcua A, Rodriguez-Palomares JF, Casas G, Pena-Pena ML, Lopes LR, Gallego-Delgado M, Franaszczyk M, Laucey G, Rangel-Sousa D, Basurte M, Palomino-Doza J, Villacorta E, Bilinska Z, Friere JL, Pinilla JM, Barriales-Villa R, Fatkin D, Sinagra G, Garcia-Pavia P, Gimeno JR, Mogensen J, Monserrat L. Elliott PM. European Cardiomyopathies Initiative Investigators. Phenotype and prognosis of dilated cardiomyopathy caused by truncating variants in the titin (TTN) gene. Circ Heart Fail 2020;13:e006832.
5. Wong GR, Nalliah CJ, Lee G, Voskoboinik A, Prabhu S, Parameswaran R, Sugumar H, Anderson RD, Ling LH, McLellan A, Johnson R, Sanders P, Kistler PM, Fatkin D*, Kalman JM*. Genetic susceptibility to atrial fibrillation is associated with atrial electrical remodelling and adverse post-ablation outcome. JACC: Clin Electrophysiol 2020;6:1509-1521. (*Co-senior authors)
6. Fatkin D, Huttner IG, Kovacic JC, Seidman JG, Seidman CE. Precision medicine in the management of dilated cardiomyopathy: JACC State-of-the-Art Review. J Am Coll Cardiol 2019;74:2921-2938.
7. Horvat C, Johnson R, Lam L, Munro J, Mazzarotto F, Roberts AM, Herman DS, Parfenov M, Haghighi A, McDonough B, DePalma SR, Keogh AM, Macdonald PS, Hayward CS, Roberts A, Barton PJ, Felkin LE, Giannoulatou E, Cook SA, Seidman JG, Seidman CE, Fatkin D. A gene-centric strategy for identifying disease-causing rare variants in dilated cardiomyopathy. Genet Med 2019;21:133-143.
8. Minoche AE, Horvat C, Johnson R, Gayevskiy V, Morton SU, Drew AP, Woo K, Statham AL, Lundie B, Bagnall RD, Ingles J, Semsarian C, Seidman JG, Seidman CE, Dinger ME, Cowley MJ, Fatkin D. Genome sequencing as a first-line genetic test in dilated cardiomyopathy. Genet Med 2019;21:650-662.
9. Huttner IG, Wang LW, Santiago CF, Horvat C, Johnson R, Cheng D, von Frieling-Salewsky M, Hillcoat K, Bemand TJ, Trivedi G, Braet F, Hesselson D, Alford K, Hayward CS, Seidman JG, Seidman CE, Feneley MP, Linke WA, Fatkin D. A-band titin truncation in zebrafish causes dilated cardiomyopathy and hemodynamic stress intolerance. Circ Genom Precis Med 2018;11:e002135.
10. Roselli C, Chaffin MD, Weng LC, Fatkin D, et al. Multi-ethnic genome-wide association study for atrial fibrillation. Nat Genet 2018;50:1225-1233.
11. Fatkin D, Santiago CF, Huttner IG, Lubitz SA, Ellinor PT. Genetics of atrial fibrillation: state of the art in 2017. Heart Lung Circ 2017;26:894-901.
12. Fatkin D, Johnson R, McGaughran J, Weintraub RG, Atherton JJ, CSANZ Genetics Writing group. Position statement on the diagnosis and management of familial dilated cardiomyopathy. Heart Lung Circ 2017;26:1127-1132.
13. Fatkin D, Huttner IG. Titin truncating mutations in dilated cardiomyopathy: the long and short of it. Curr Opin Cardiol 2017;32:232-238.
14. Wang LW, Huttner IG, Santiago CF, Kesteven SH, Yu ZY, Feneley MP, Fatkin D. Standardized echocardiographic assessment of cardiac function in normal adult zebrafish and heart disease models. Dis Model Mech 2017;10:63-76.