Professor Jamie Vandenberg
Professor

Professor Jamie Vandenberg

1985         Bachelor of Science (Medical) – Distinction (University of Sydney)

1988         Bachelor of Medicine and Bachelor of Surgery – Honors (I) (University of Sydney)

1994         Doctor of Philosophy (University of Cambridge)

 

Medicine & Health
Victor Chang Cardiac Research Institute

Research Interests: Biophysics and pharmacology of cardiac ion channels. Genotype-Phenotype relationships in inherited arrhythmia syndromes. In silico modeling of inherited arrhythmia syndromes. Structural basis of drug binding to hERG K+ channels.

Professor Jamie Vandenberg completed his medical degree at the University of Sydney (1988) and his PhD in the Department of Biochemistry at the University of Cambridge (1994). He undertook postdoctoral studies in cardiac electrophysiology at the University of Oxford then moved to the University of Cambridge where he established an independent group looking at the molecular basis of cardiac arrhythmias. In 2002, he relocated to the Victor Chang Cardiac Research Institute, where he is currently Co-Deputy Director and Head of the Mark Cowley Lidwill Research Program in Cardiac Electrophysiology. He is a National Health and Medical Research Council Principal Research Fellow, and in 2015 was elected to the Fellowship of the Heart rhythm Society (USA) and the Australian Academy of Health and Medical Sciences. His research has focused on the molecular basis of cardiac electrical activity and understanding the genesis of cardiac arrhythmias and sudden cardiac death.  

Phone
02 9295 8771
Location
Victor Chang Cardiac Research institute Lowy Packer Building, 405 Liverpool Street, Darlinghurst, NSW 2010, Australia

Current Research Grants

NHMRC Principal Research Fellowship (2017-2021) Vandenberg JI $838,875

NHMRC Program Grant (2015-2019). Finding new evidence based therapies for treating heart disease and stimulating Regeneration. RP Harvey, RM Graham, PS Macdonald, D Fatkin, SL Dunwoodie, JI Vandenberg $10,600,000

NHMRC Project Grant (2018-2020). The structural basis for promiscuity of drug binding to hERG K+ channels. JI Vandenberg, AG Stewart TW Allen, E Perozo $713,035

 

Awards

1992         International Society of Heart Research Young Investigator Travel Award

1992         American Heart Association Melvyn L. Marcus Young Investigator Award in Integrated Physiology (finalist)

1994         Gedge Prize (for best research undertaken by a student in Physiological Sciences) at University of Cambridge

2014         National Lecturer (Australian Physiological Society)

2015         Sir Bob Robertson Award (Australian Society for Biophysics)

2015         Elected Fellow of the Heart Rhythm Society, USA

2015         Elected Fellow, Australian Academy of Health and Medical Sciences

2018         Elected Fellow, International Society of Heart Research

 

Scholarships and Fellowships

1984         AMSA-AMA B.Sc.(Med.) Scholarship

1990-91   Sir Robert Menzies Memorial Scholarship in Medicine

1990-92   Overseas Research Scholar Award - Department of Education, UK

1992-93   Sydney University Medical Foundation Sir Zelman Cowan Traveling Research Fellowship 

1993-95   Zeneca Junior Research Fellowship, Pembroke College, Oxford, UK

1996-01   British Heart Foundation Basic Science Award

1996-01   British Heart Foundation Basic Science Award (resigned December 2001)

2002-06   NHMRC RD Wright Career Development Award in Biomedical Science

2007-11   NHMRC Senior Research Fellowship Level A

2012-16   NHMRC Senior Research Fellowship Level B with SEO (translation)

2017-21   NHMRC Principal Research Fellowship with SEO (translation)

Jamie Vandenberg’s work focuses on the molecular basis of inherited and drug-induced arrhythmia syndromes. He has made major contributions to understanding of the molecular and structural basis of ion channel gatingandmechanisms underlyingdrug binding to hERG K+channels, the cause of the vast majority of cases of drug-induced arrhythmias. He has also made significant contributions to understanding the molecular basis of inherited arrhythmia syndromescaused by ion channel mutations. His work exemplifies how the combination of a deep understanding of basic biology combined with the study of clinically relevant problems can have significant translational benefits both in terms of the management of families with inherited heart rhythm disorders and in the industrial setting in terms of development of better assays to assess the pro-arrhythmic risk of drugs in the preclinical setting.

Molecular and structural basis of ion channel gating

Jamie was the intellectual driving force behind the discovery of the “Japanese Puzzle Box” model of inactivation gating in hERG K+ channels. His work characterising the kinetics of hERG K+ channel gating has also become accepted as the gold standard for the field and has been adopted by the Food and Drug Administration as the reference data set for establishing in silicomodels of hERG K+ channel gating.

Drug-induced arrhythmias

In addition to providing strong evidence for the state-dependence of drug binding to hERG K+ channels, in 2014 he reported the first direct measurements of the kinetics of binding and unbinding of drugs to hERG K+ channels. This work provides the groundwork for the development of molecularly accurate in silico models of hERG drug binding that can be used to predict the pro-arrhythmic risk of drugs from preclinical screening assays.

Molecular basis of inherited arrhythmia syndromes

Together with Andrew Grace and Bill Colledge we developed the first animal model of Brugada Syndrome. By adapting a clinical premature stimulation protocol we also demonstrated that the arrhythmia mechanism in the mouse was the same as that in humans. More recently, Jamie has had a very productive collaboration with Diane Fatkin’s molecular genetics group. Together, we demonstrated how gene-environment interactions contributed to the genesis of familial atrial fibrillation, developed novel computational tools to explain the epistatic effects of potassium channel variation on cardiac repolarization and atrial fibrillation risk and identified a gene-guided therapy for a family with an inherited dilated cardiomyopathy.

Computational cardiology

Together with Adam Hill, Jamie has used computational modeling to complement their ion channel gating work for >10 years. Significant breakthroughs in recent years include the development of whole heart models based on graphical processor unit technology, which has enabled breakthrough discoveries in establishing causally cohesive links from genotype to whole organ phenotypes. His laboratory has also applied partial least square methods to permit the analysis of large populations of “genetically different” individuals to understand the variable penetrance of dominant molecular defects.

 

1. Molecular basis of gating in hERG K+ channels

  • Wang DT, Hill AP, Mann SA, Tan PS, Vandenberg JI. Mapping the sequence of conformational changes underlying selectivity filter gating in the K(v)11.1 potassium channel. Nat Struct Mol Biol. 2011 Jan;18(1):35-41.
  • Perry MD, Ng CA, Vandenberg JI. Pore Helices Play a Dynamic Role as Integrators of Domain Motion during Kv11.1 Channel Inactivation Gating. J Biol Chem. 2013; 288(16): 11482-91
  • Phan K, Ng CA, David E, Shishmarez D, Kuchel PW, Vandenberg JI, perry MD. The S1 helix critically regulates the finely-tuned gating of Kv11.1 channels. J Biol Chem (2017) In Press.

2. Genoptype-phenotype relationships in inherited arrhythmia syndromes

  • Mann SA, Castro ML, Ohanian M, Guo G, Zodgekar P, Sheu A, Stockhammer K, Thompson T, Playford D, Subbiah RN, 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(16):1566-73
  • Perry MD, Ng CA, Phan K, David E, Steer K, Hunter MJ, Mann SA, Imtiaz M, Hill AP, Ke Y, Vandenberg JI. Rescue of protein expression defects may not be enough to abolish the pro-arrhythmic phenotype of long QT type 2 mutations. J Physiol. 2016; 594(14): 4031-49

3. Development of ECG biomarkers for risk of sudden cardiac arrest

  • Immanuel SA, Sadrieh A, Baumert M, Couderc JP, Zareba W, Hill AP, Vandenberg JI. T-wave morphology can distinguish healthy controls from LQTS patients. Physiol Meas. 2016; 37(9): 1456-73.

 4. Structural basis of hERG K+ channel function

  • Vandenberg JI, Perozo E, Allen TW. Towards a Structural View of Drug Binding to hERG K(+) Channels. Trends Pharmacol Sci. 2017 Oct;38(10):899-907. 
  • Ng CA, Hunter MJ, Perry MD, Mobli M, Ke Y, Kuchel PW, King GF, Stock D, Vandenberg JI. The N-Terminal Tail of hERG Contains an Amphipathic α-Helix That Regulates Channel Deactivation. PLoS One. 2011 Jan 13;6(1):e16191
  • Vandenberg JI, Perry MD, Perrin MJ, Mann SA, Ke Y, Hill AP. hERG K+ channels: Structure, Function and Clinical Significance. Physiological Reviews 2012; 92(3):1393-1478

My Research Supervision

Post-doctoral fellows:

Matt PERRY: Cardiac disease modelling using induced pluripotent stem cells

Andy NG: Genotype-phenotype relationships in Long QT syndrome

Carus LAU: Structural analysis of hERG K+ channels

Jordan THORPE: Modeling heart disease using cardiac organoids

PhD Students

Nicholas KERR: Induced pluripotent stem cell models of Brugada Syndrome

Honours Students

Whitney Liang: Investigating the role of cellular heterogeneity in cardiac electrical signalling

Emily Hurley: Modeling Atrial arrhythmias using induced pluripotent stem cells

Connie Jiang: Genotype-phenotype relationships in Long QT syndrome

Wei Han: Structural analysis of hERG K+ channels

My Teaching

School of Medical Sciences, Cardiovascular Physiology, Yr3: Cardiac Arrhythmias

Medicine Yr3: Anti-arrhythmic drugs