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CARIM Newsletter December 2016
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This newsletter contains information on the following subjects:
  • Career development award Thomas van Sloten
  • NEW: Translational trends
  • NEW: Paramount papers
  • Who's new?!
  • Grant deadlines
  • Cardiovascular Grand Rounds Maastricht
  • Symposia & other lectures
  • Academic events
  • Media appearances

CARIM newsletter


Contributions for the newsletter (e.g. news of events and grants, important publications, societial impact related topics and research results related to CARIM's research) can be sent to carim-office@maastrichtuniversity.nl. Please submit the text in English and include a short title. The text should be max. 200 words. If applicable, include high resolution pictures and other documents.

As from this edition, two regular sections are added: "Paramount papers" and Translational trends". So, if you have a top publication or a translational development worth mentioning, please contact CARIM Office. 

Career development award Thomas van Sloten

Thomas van Sloten (Department of Internal Medicine and The Maastricht Study) received the Career Development Award at the annual Artery meeting of the Artery Society in Copenhagen (October 13, 2016). 

Translational trends

“Hard” disease - “Rock”ing between clinical and fundamental science


Today, conventional diagnostic tools fail to predict aortic valve stenosis. In an effort to bridge this gap, and to engage in strategies for prevention and regression of calcification, research between CARIM and HVC combines knowledge on the molecular, biological and clinical processes implicated in aortic valve stenosis progression. Currently, a double blind, placebo controlled trial on the efficacy of vitamin K on aortic valve calcification has been launched.

Translational research combining expertise between Departments of Biochemistry, Cardiology, Clinical Chemistry, and Nuclear Medicine will propel the biological and medical expertise to support a translational approach that will enable better risk prediction and benefit patients by identifying aortic stenosis leading to optimal treatment.

Aortic valve stenosis - narrowing of the aortic valve - is a common type of valvular disease, well-known for its progressive character. Yet, diagnosing is only possible when aortic valve stenosis is already severely progressed with emerging importance of calcification. Unfortunately, to date, no effective pharmacological treatment is available to alter its course and surgical intervention remains the only treatment option in severe aortic valve stenosis. Thus, there is an unmet clinical need to reverse or delay processes driving the progression of the disease. Therefore, it is crucial to understand these pathophysiologic processes at a molecular level.

Combined translational efforts between basic research Departments and clinical Departments have highlighted imaging of micro-calcifications in cardiovascular disease using state of the art imaging with novel radiotracers. Additionally, Leon Schurgers from the Department of Biochemistry identified molecular and biological mechanisms leading to micro-calcifications associated with aortic valve stenosis and revealed that vitamin K-dependent proteins are involved. Matrix Gla-protein is such vitamin K-dependent protein involved in the inhibition of calcification, and Frederique Peeters from Cardiology identified that vitamin K-antagonist treatment results in accelerated progression of vascular and valvular calcification.

Therefore, they initiated and started a double blind, placebo controlled trial with supplementation of vitamin K2 in patients that are diagnosed with aortic valve calcification. In this collaboration between Frederique Peeters and Leon Schurgers, with the involvement of Harry Crijns, Bas Kietselaer, Steven Meex, Joachim Wildberger and Jan Bucerius, state of the art PET-MRI imaging is applied to visualise possible beneficial effects of vitamin K supplementation on inhibition of valve calcification progression.

Paramount papers

 

Frivolous Friendships by Kissing Chemokines


Disruption or enhancement of protein-protein interactions (PPIs) as therapeutic intervention is currently applied to the inflammatory chemokine field as a result of the discovery that chemokine heterodimerization is involved in many pathological processes, such as cancer, atherosclerosis and HIV. Potentially, modulating these chemokine PPIs could lead to therapies preventing the detrimental effects of hetero-dimerization while maintaining normal chemokine function.

However, it is unclear if the actual physical formation of chemokine heterodimers or the additive effects of combined receptor stimulation are the underlying cause of the pathological processes. For this reason Stijn Agten from CARIM's Department of Biochemistry in collaboration with Ludwig Maximilian's University in Munich (Weber) and the University of Minneapolis (Mayo) designed a synthetic route for general chemokine heterodimer generation and synthesized a covalently bound heterodimer of chemokines RANTES and PF4. The total chemical synthesis of the heterodimer was achieved using fragment peptide synthesis combined with native chemical ligation and a conformation-assisted oxime ligation in the final step. This heterodimer exhibited increased biological activity compared to the mixed individual chemokines, unambiguously proving that physical heterodimerization is the cause of the functional enhancement leading to pathological processes. Moreover, with this proof of concept, other covalently bound chemokine heterodimers can be synthesized to decipher the mechanisms by which they act. This high profile chemical biology paper was recently published in Angewandte Chemie International Edition: http://onlinelibrary.wiley.com/doi/10.1002/anie.201607036/epdf

In addition, the paper has been picked up by the Royal Netherlands Society of Chemistry as a trending topic in their C2W newsletter: http://www.c2w.nl/nieuws/gedwongen-huwelijk-toont-ware-aard-eiwitten/item18689

 

Paper by CARIM researchers published in JACC


Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease characterized by ventricular arrhythmias and progressive right ventricular (RV) dysfunction. Familial ARVC is known for reduced penetrance and variable disease expression that ranges from sudden cardiac death in young individuals to lifelong absence of any phenotype. Presently, ARVC is divided into 3 consecutive clinical stages: 1) subclinical (concealed), with neither electrical nor structural abnormalities; 2) electrical, with only electrocardiographic (ECG) abnormalities; and 3) structural, with both electrical and structural abnormalities. 

In close collaboration with researchers from UMC Utrecht, we investigated the value of echocardiographic myocardial deformation imaging for diagnostic stratification of ARVC mutation carriers, aiming at the detection of early-stage disease expression. We found that half of the functionally normal mutation carriers (subclinical stage) exhibit RV deformation abnormalities without detectable ECG or structural substrates according to current Task Force Criteria. Through CircAdapt model simulations of RV tissue mechanics we demonstrated that these RV deformation abnormalities were indicative of regional mechanical dysfunction, despite the absence of detectable fibrosis (late gadolinium enhancement). Furthermore, electrical activation delay alone could not explain the deformation abnormalities observed. We therefore concluded that mechanical dysfunction can precede electrical abnormalities in ARVC, and that RV deformation imaging can potentially improve the detection of the earliest stages of this challenging disease. This unique combination of clinical imaging data and computer simulations challenges the current staging criteria for ARVC. Prospective clinical studies are needed to demonstrate the benefit of echocardiographic deformation imaging in arrhythmic risk stratification for ARVC mutation carriers.

Thomas P. Mast, MD, Arco J. Teske, MD, PhD, John Walmsley, PhD, Jeroen F. van der Heijden, MD, PhD, René van Es, PhD, Frits W. Prinzen, PhD, Tammo Delhaas, MD, PhD, Toon A. van Veen, PhD, Peter Loh, MD, PhD, Pieter A. Doevendans, MD, PhD, Maarten J. Cramer, MD, PhD, Joost Lumens, PhD 

Right ventricular deformation imaging and computer simulation for electromechanical substrate characterization in arrhythmogenic right ventricular cardiomyopathy. 

J Am Coll Cardiol 2016;68(20):2185-2197. [IF = 17.759]

Link paper
Link Editorial by F. Marchlinski and T. Edvardsen

Who's new?!


Hi, my name is Lisa van der Vorm. I recently obtained my Master's degree in Biomedical Sciences at the Radboud University Nijmegen. In September 2016 I started as a Ph.D. student at Synapse Research Institute here in Maastricht. Part of my project is the development of new assays for coagulation factors, which I will work on at Synapse. Furthermore, in collaboration with the Gelre Hospital in Apeldoorn I will set up a biobank, a large-scale collection of samples from patients with a variety of diseases, to study hemostasis and thrombosis with the newly-developed assays.

Grant deadlines

DOWNLOAD HERE THE SUBSIDY CALENDAR FOR 2016

Dr. E. Dekker Junior Postdoc - Deadline January 24, 2017
Click here for more information

Dr E. Dekker Arts in opleiding tot specialist - Deadline January 24, 2017
Click here for more information


NWO Veni- Deadline January 10, 2017
Click here for more information

Updated procedure AXA Post-Doctoral fellowship 2016-2017

Due to changes in the selection procedure by the AXA Research Fund, we have need forced to change the deadline for the internal selection procedure for the AXA Post-Doctoral fellowship 2016-2017 to May 8, 2017 at noon.

If you are interested in a fellowship of €130.000,- (for a period of maximum 2 years) for research that contributes to the knowledge and understanding of risks, than read the (updated) procedure and apply.
For more information contact your funding advisor.

 


December 9 - Lars H. Lund, Md, PhD, Karolinska Institute, Stockholm, Sweden
"Heart failure with preserved and mid-range ejection fraction: lessons from registries"

December 16 - Lars Maegdefessel, MD, PhD, Karolinska Institute, Stockholm, Sweden
"Non-coding RNAs in vascular disease detection and therapy"

January 13 - Joris Ector, MD, PhD, Katholieke Universiteit Leuven, Belgium
"Journey to the center of the hEART: 3D cardiac imaging anno 2017"

January 20 - Giuseppe Bianchi, MD, San Rafaele University Milano, Italy
"Unveiling causality in genotype-phenotype relationships by drug therapy"


Starts at 7.45 am, Academic hospital Maastricht, Meeting room A3-B3, level 3
Breakfast included! Registration not necessary


Click here for an overview of all the CGRM lectures of the last quarter of 2016

Maastricht Consensus Conference on Thrombosis (MCCT) - February 22-24, 2017

The Maastricht Consensus Conference on Thrombosis (MCCT) takes place from February 22-24 in the Maastricht Exhibition & Congress Centre (MECC). The MCCT will be a hybrid meeting containing both active as well as more "passive" elements (intensive workshops, and plenary lectures). Consensus will be sought on future directions for research.

The Maastricht Consensus Conference on Thrombosis will be theme-focused and will involve clinicians, epidemiologists and basic scientists, who will jointly explore new avenues for research in the area of thrombosis and haemostasis. The Maastricht Consensus Conference on Thrombosis is a 3 day meeting, involving plenary lectures by prominent scientists and experts in the field on a chosen theme, followed by highly interactive, intensive workshops in which the interaction between the experienced scientists, PhD students and postdocs is used to explore gaps in research or knowledge on specific topics.

Click here for more information.

Symposia & events

Workshop "Writing Successful ERC CoG Grants" - December 7, 2016 
Click here for more information

Vici lunch session - December 8, 2016
Click here for more information

Lecture Dr. Margreet de Vries - December 9, 2016
Click here for more information


Maastricht AF - Crossing Borders - February 8-10, 2017
Click here for more information

Revolution in Biomedicine summer programme Imperial College London - July 3-28, 2017
Click here for more information

Agenda KNAW November/December

Academic events

PhD Conferral Ralph Kurstjens, Wednesday December 14, 10.00 hours
Supervisors: Prof. C.H.A. Wittens; Prof. J.E. Wildberger
Co-supervisor: Dr R. de Graaf
Title: "haemodynamics in Deep Venous Obstruction"

PhD Conferral Anna-Margaretha Karmann-Sailer, Wednesday December 14, 12.00 hours
Supervisors: Prof. G.W.H. Schurink; Prof. M.W. de Haan
Co-supervisor: Dr C.R.L. Jeukens
Title: "Multimodel image fusion in endovascular complex aortic aneurysm repair"

PhD Conferral Stijn Agten, Thursday December 15, 16.00 hours
Supervisor: Prof. T.M. Hackeng
Co-supervisor: Dr R. Koenen
Title: "Oximation optimization and applications in cariovascular research"

Media appearances


Jordi Heijman (Dept. of Cardiology) - Limburgs Dagblad, 05-11-2016: "Jordi Heijman groot wetenschappelijk talent"

Jordi Heijman (Dept. of Cardiology) - Limburgs Dagblad, 05-11-2016: "De wiskunde van het hart"
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