2017 is off to a good start for the lab with the publication of a podcast on cardiac computational modeling presented by Jordi Heijman, which was published on the website of the ‘Scientists of Tomorrow’ of the European Society of Cardiology (ESC). In this podcast, which was recorded during a visit to the University of Göttingen, Jordi describes some of the basic methods for computational modeling of cardiac electrophysiology and gives a demonstration of the Myokit software tool.
The podcast can be found here.
Heart failure (HF) remains a common cause of death and disability and is associated with altered signal transduction via b-adrenoceptors and G proteins, resulting in reduced adenylyl cyclase-mediated cAMP formation and contributing to contractile dysfunction. Nucleoside diphosphate kinases (NDPKs) can modulate G-protein activity and are enriched at the plasma membrane of end-stage HF patients. However, their relevance for HF pathophysiology is largely unknown, particularly for the NDPK‑C isoform.
Together with collaborators from various centers in Germany and abroad, Jordi Heijman published a study in the most recent edition of Circulation, showing for the first time a potential critical role for NDPK-C in the suppression of cAMP formation in HF patients. In particular, this study identified that NDPK-C is crucial for the interaction between NDPKs and G proteins, building complexes and scaffolding them at the plasma membrane. These interactions regulate cAMP levels and cardiomyocyte contractility. In HF patients, NDPK-C switched from predominantly Gas stimulation to activation of Gai. Our findings provide a potential mechanism for the detrimental decrease in cAMP and related dysfunction previously described in HF patients, and position NDPK‑C as a novel critical determinant of bAR/cAMP signaling that contributes to impaired cardiac function and remodeling in human HF.
Reference: Abu-Taha IH*, Heijman J*, Hippe HJ, Wolf NM, El-Armouche A, Nikolaev VO, Schäfer M, Würtz CM, Neef S, Voigt N, Baczkó I, Varró A, Müller M, Meder B, Katus HA, Spiger K, Vettel C, Lehmann LH, Backs J, Skolnik EY, Lutz S, Dobrev D#, Wieland T# (2016) Nucleoside Diphosphate Kinase-C Suppresses cAMP Formation in Human Heart Failure. Circulation, Published online on Dec 7, 2016. *equally contributing first authors, #co-senior and co-correspondence authors – [PubMed]
In response to the New Scientist nomination and the recent newspaper article in Dagblad de Limburger, Jordi Heijman has been asked to appear on the daily evening show of the local TV channel L1 called ‘Avondgasten‘. The show will be recorded on Tuesday, November 29, 2016 and will air that same evening at 17:55 h, with re-runs on 20:55 and 22:55 hours. In the show, Jordi will discuss his research on computational approaches to understand heart rhythm disorders.
Update November 30, 2016: The video of the interview can be found here
In response to the nomination by New Scientist, Jordi Heijman was interviewed by the local newspaper ‘Dagblad de Limburger’. The resulting article, entitled ‘The mathematics of the heart’ was published Saturday, November 5th.
During the 2016-2017 academic year, Bart van Sloun, a master student in the Systems Biology research master at Maastricht University, will write his thesis in the team. Bart will investigate subcellular structure-function relationships that influence cardiomyocyte calcium handling using super-resolution microscopy and computational modeling.
For the second time, the New Scientist organization is awarding the title “Wetenschapstalent” (scientific talent) to a young researcher from Belgium or The Netherlands. Based on recommendations from all universities in both countries, the jury has selected 25 candidates from various disciplines. Jordi Heijman has been selected as one of these 25 candidates. The 5 finalists and final winner will be selected by combining votes from a jury with a popular vote from visitors to the New Scientist website. More information, and the option to vote, can be found at http://www.newscientist.nl/talent/.
We are looking for a motivated PhD student to join our team and work on a project about integrative computational modeling of cardiomyocyte calcium-handling. In this project, you will participate in ongoing experimental research (in particular confocal microscopy and patch-clamp experiments) to delineate the cellular and molecular mechanisms of cardiac arrhythmias. You will employ the thereby generated data to develop novel dynamic computational models (programmed in C++ and Matlab) to investigate the potential central role of (abnormal) Ca2+ handling in cardiac arrhythmogenesis. These models can be employed to integrate available data, design future experiments, predict potential effects of (antiarrhythmic) drugs, and extrapolate molecular and cellular findings to a multi-cellular environment, thereby providing important new insights to improve the treatment of cardiac arrhythmias.
The ideal candidate has successfully completed a master’s degree (or equivalent) in biomedical engineering, biochemistry, molecular biology, medicine, or related disciplines. He/she has a strong intrinsic motivation to commit to a 4 year PhD-program, a demonstrable interest in cardiovascular research, and an analytical mindset. Previous experience with computational modeling / programming experience, or relevant experimental techniques in molecular biology or electrophysiology is considered a plus.
The first of two whitepapers about K+-channel (dys)regulation in the heart that were written based on presentations and discussions during the 4th UC Davis Cardiovascular Symposium that took place March 3-4, 2016 in Davis, has now been accepted for publication in The Journal of Physiology. This first paper describes the structural basis of voltage-gated K+-channel function, as well as the mechanisms involved in regulation of K+ channel gating, expression, and membrane localization. The full citation is as follows:
Grandi E, Sanguinetti MC, Bartos DC, Bers DM, Chen-Izu Y, Chiamvimonvat N, Colecraft H, Delisle BP, Heijman J, Navedo MF, Noskov S, Proenza C, Vandenberg JI, Yarov-Yarovoy V. Potassium channels in the heart: Structure, function and regulation. J Physiol. 2016.
This is the start of the new website, which will provide information about some of the results from the lab.