Inherited Heart
Diseases 

"If we can identify family members at risk
even before any symptoms develop,
we can intervene straight away, which may
help delay or stop their progression
to severe heart failure,"

- Professor Diane Fatkin 


Professor Diane Fatkin

head, inherited diseases laboratory

Research Overview

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.

Research projects

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 as a new approach for mutation detection in families. 

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.

Laboratory Members

Laboratory 

Claire Horvat, Postdoctoral Scientist 

Renee Johnson, Clinical Research Coordinator 

Inken Martin, Senior Postdoctoral Scientist 

Jasmina Cvetkovska, Research Assistant 

Celine Santiago, PhD Student 

Magdalena Soka, Research Assistant 

Gunjan Zhao, Research Assistant 

Publication Highlights

1. Mann SA, Otway R, Guo G, Soka M, Karlsdotter L, Trivedi G, Ohanian M, Zodgekar P, Smith RA, Wouters MA, Subbiah R, Walker B, Kuchar D, Sanders P, Griffiths L, Vandenberg JI, Fatkin D. Epistatic effects of potassium channel variation on cardiac repolarization and atrial fibrillation risk. J Am Coll Cardiol 2012;59:1017-1025. 

2. Mann SA, Castro ML, Ohanian M, Guo G, Zodgekar P, Sheu A, Stockhammer K, Thompson T, Playford D, Subbiah R, Kuchar D, Aggarwal A, Vandenberg JI, Fatkin D. R222Q SCN5A mutation is associated with reversible ventricular ectopy and dilated cardiomyopathy. J Am Coll Cardiol 2012;60:1566-1573.

3. Liang B, Soka M, Christensen AH, Olesen MS, Larsen AP, Knop FK, Wang F, Nielsen JB, Andersen MN, Humphreys D, Mann SA, Huttner IG, Vandenberg JI, Svendsen JH, Haunsø S, Preiss T, Seebohm G, Olesen SP, Schmitt N, Fatkin D. Genetic variation in the two-pore domain potassium channel, TASK-1, may contribute to an atrial substrate for arrhythmogenesis. J Mol Cell Cardiol 2014;67:69-76.

4. Cannon L, Yu ZY, Marciniec T, Waardenberg AJ, Iismaa SE, Nikolova-Krstevski V, Neist E, Ohanian M, Qiu MR, Rainer S, Harvey RP, Feneley MP, Graham RM. Fatkin D. Irreversible triggers for left ventricular hypertrophy are established in the early postnatal period. J Am Coll Cardiol 2015;65:560-569.

5. Christensen AH, Chatelain FC, Huttner IG, Olesen MS, Soka M, Feliciangeli S, Horvat C, Santiago CF, Vandenberg JI, Schmitt N, Olesen SP, Lesage F, Fatkin D. The two-pore domain potassium channel, TWIK-1, has a role in the regulation of heart rate and atrial size. J Mol Cell Cardiol 2016;97:24-35.

6. Christensen AH, Chatelain FC, Huttner IG, Olesen MS, Soka M, Feliciangeli S, Horvat C, Santiago CF, Vandenberg JI, Schmitt N, Olesen SP, Lesage F, Fatkin D. The two-pore domain potassium channel, TWIK-1, has a role in the regulation of heart rate and atrial size. J Mol Cell Cardiol 2016;97:24-35.

7. 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. 

8. Fatkin D, Huttner IG. Titin truncating mutations in dilated cardiomyopathy: the long and short of it. Curr Opin Cardiol 2017 (in press)

9. Fatkin D, Johnson R, McGaughran J, Weintraub RG, Atherton JJ. Position statement on the diagnosis and management of familial dilated cardiomyopathy. Heart Lung Circ 2017 (in press)

10. Fatkin D, Santiago CF, Huttner IG, Lubitz SA, Ellinor PT. Genetics of atrial fibrillation: state of the art in 2017. Heart Lung Circ 2017 (in press)

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