Christine Klein, Philip Seibler, Stephanie Stoelting, Anne Grünewald and Jeanette Erdmann, as future founders of iPS-HL, were awarded the Gründerpreis „BioMedTec 2014“ of the Sparkasse zu Lübeck AG. This prize is awarded every two years since 2008 with 10.000€.
Currently, all over the world large-scale projects aiming at sequencing thousands of probands get kicked-off, like the „precision medicine initiative“ in the US, the 100,000 Genomes initiative in UK, or the 50,000 Genome sequencing project in Saudi-Arabia, just to name a few.
The potential of large-scale genome sequencing project is very well justified in a speech held by President Barack Obama at the White House earlier this year to kick-off the „precision medicine initiative“.
Unfortunately, in Germany no large-scale genome sequencing project is on the horizon and it seems like German genome researchers might loose their leading role in the field.
An essay (in German) asking about the future role of German researchers in the field of Genomics has been published in the Laborjournal by Heribert Schunkert and Jeanette Erdmann.
Starting with a severely affected family, a research team led by Jeanette Erdmann, Christian Hengstenberg and Heribert Schunkert (Institut für Integrative und Experimentelle Genomik, University of Lübeck and Deutsches Herzzentrum München) identified a novel mechanism leading to myocardial infarction. Specifically, the scientists detected two mutations that jointly blocked nitric oxide signalling in platelets leading to accelerated thrombus formation. Another variant of the same enzyme, affecting a large proportion of the population, was also found to affect coronary risk, albeit to a much lesser extend. The work was published on December 13th, 2013 in the prestigious journal Nature.
Link: http://www.nature.com/nature/journal/v504/n7480/full/nature12722.html
For long it is known that shorter adult height is associated with an increased risk of coronary artery disease. This association is mainly explained by
by the association between shorter height and an adverse lipid profile.
A collaborative effort with national and international colleagues led by Nilesh Samani (University of Leicester) studied the association between height-associated
genetic variants and CAD.
The main advantage of our genetic approach is that it reduces the likelihood of known and unknown demographic, lifestyle, socioeconomic, or behavioral
confounders that have an independent effect on height and the risk of CAD and could give rise to a false association between the two factors.
It is possible that the association between the studied genetic variants and height and the association with CAD are through completely different mechanisms. However, the more likely scenario on the basis of our findings is that height variants affect biologic pathways, which on the one hand determine achieved height and on the other hand
influence the risk of CAD. It is also possible that genetically determined height itself alters lifestyle or behavior, which then affects the risk of CAD.
The study is published online in the New England Journal of Medicine.
Thorsten Albig, the Prime Minister of Schleswig-Holstein, started his „Summer Tour“ at the University of Lübeck. He was interested to learn more about the members of the Institute and its research agenda.
In a collaborative study, mainly between Munich (Thorsten Kessler and Heribert Schunkert) and colleagues from the Department of Physiology and Pathophysiology in Beijing (Lu Zhang and Wei Kong), as well as Cor de Wit and Kjestine Schmidt from the University of Lübeck, members of the IIEG (Zouhair Aherrahrou as shared senior author and Jeanette Erdmann) have identified a novel mechanism by which ADAMTS-7 affects neointima formation.
ADAMTS-7, a hitherto rather unknown gene, had been found to be genome-wide significantly associated with coronary artery disease (CAD) by CARDIoGRAM, a consortium lead by Heribert Schunkert, Nilesh Samani and Jeanette Erdmann. However, the mechanisms that link ADAMTS-7 and CAD risk remained elusive.
Here, by employing transgenic mice we now revealed that ADAMTS-7 plays a pivotal role in vascular remodelling. After vascular injuryAdamts7-/- mice were resistant to neointima formation. Thus, inhibition of ADAMTS-7 might represent a promising therapeutic strategy for the prevention of restenosis after PCI. Moreover, Adamts7-/- mice displayed accelerated re-endothelialisation. As drug-eluting stents designed to reduce restenosis rates may actually retard re-endothelialisation – and thereby provoke stent thrombosis – the finding that ADAMTS-7 affects both processes may be of interest. In fact, inhibition of ADAMTS-7 may solve two problems at once, i.e. decrease restenosis and augment re-endothelialisation. Furthermore, the identification of thrombospondin-1 as an ADAMTS-7 target on one hand and as a modulator of vascular remodelling on the other hand might lead to the elucidation of further druggable downstream targets.
Link to the paper:
http://circ.ahajournals.org/content/early/2015/02/20/CIRCULATIONAHA.114.014072.abstract
The IIEG was involved in one of the largest epigenome-wide association studies (EWAS) of its kind, in which we have identified a new genetic mechanism that may play a role in mediating some of the harmful effects of becoming overweight, such as diabetes.
In this study, published in The Lancet, Samani and colleagues looked at epigenetic changes in DNA in relation to body mass index (BMI), a widely used measure of obesity. One particular type of epigenetic change, a process known as DNA methylation, was examined. DNA methylation involves specific locations along the DNA called cytosine bases being modified through the addition of methyl chemical groups.
We used microarray technology to measure methylation levels at over 351 000 sites across the genome using whole blood DNA samples taken from 459 individuals of European origin, and identified five sites where the level of methylation correlated with BMI.
We found that for every 10% increase in methylation at the most significant site—cg22891070—BMI increased by 3·6%, equating to about 0·98 kg/m2 for a person in the original cohort with an average BMI of 27 kg/m2. In comparison, the obesity risk gene, FTO, accounts for a more modest 0.39kg/ m2 increase in BMI.
However, further studies are needed to understand how and when obesity affects methylation at HIF3A and what the consequences are, but the findings could eventually lead to new treatments that may tackle the adverse effects of obesity on health.
At a more general level, our study shows that investigating epigenetic changes in DNA may reveal new mechanisms involved in common diseases.
Two projects applying system medicine approaches to unravel the pathogenesis of atherosclerosis and inflammatory diseases started in 2014 with funding by the BMBF.
The IIEG is co-leading e:AtheroSysMed together with Prof. Schunkert (DHM) and is partner in SYSinflame aiming to understand the shared genetic basis of psoriasis and atherosclerosis.
Link: http://www.gesundheitsforschung-bmbf.de/de/5133.php www.AtheroSysMed.de
Congratulations! Mariana defended very sucessfully her master thesis about „Prevalence of familial hypercholesterolemia variants in the exome data of myocardial infarction patients“. She is the first master student officially affiliated with the IIEG! And she will now start her PhD at the IIEG!
According to the German magazine „Laborjournal“ the IIEG is among the top 5 cardiovascular research institutes in Germany based on publications and citations in the years 2008 to 2012
