Hennekam Syndrome on Michael’s Domain

Best paper award

Fri, 01 May 2015 00:00:00 +0000

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![](/sites/]( http://www.med.helsinki.fi/english/news/2015/20150505_Jeltsch.html)We have won Circulation’s 2014 Best Paper Award in the category of Basic Science. Circulation is the leading cardiology journal and the organ of the American Heart Association . Already when we published the paper (titled [/files/files/Jeltsch%20et%20al.%20-%202014%20-%20CCBE1%20Enhances%20Lymphangiogenesis%20via%20A%20Disintegrin.pdf">“CCBE1 Enhances Lymphangiogenesis via A Disintegrin and Metalloprotease With Thrombospondin Motifs-3–Mediated Vascular Endothelial Growth Factor-C Activation”](/sites/<?php print $_SERVER[)), it was clear that it provided a major overhaul of our understanding of the VEGF-C growth factor and it got featured by Open Heart . The article manages to provide multiple new insights:

New Mechanisms of Lymphangiogenesis and Lymphedema

Fri, 26 Sep 2014 00:00:00 +0000

Here is the presentation that I could not give, because my schedule was too tight to allow for a 1 hour 20 minute delay. If you have questions concerning the talk, please ask via e-mail: michael@jeltsch.org.My Lufthansa flight LH855 from Helsinki to Frankfurt got delayed by 1 hour 20 minutes. Because I had only 1 hour 15 minutes to change my plane in Frankfurt on my way to the 40th Congress of the European Society of Lymphology in Genova/Italy, I did not even board the plane and rather canceled my talk. Because I have another appointment on Saturday in Germany, I had planned the return flight for Friday early morning and hence could not move my talk either. Next time I’ll be smarter.

We got featured by Circulation!

Mon, 12 May 2014 00:00:00 +0000

The molecular basis of Hennekam syndrome

Thu, 20 Feb 2014 00:00:00 +0000

Finally our CCBE1 manuscript is out! You can access it from the Circulation’s homepage . If your library does not have a subscription, just drop me an e-mail . It nicely complements the article by Le Guen et al. from Ben Hogan’s group in Development. While Le Guen and colleagues analyzed the interaction of CCBE1 with the VEGF-C/VEGFR-3 pathway mainly at the genetic level in zebrafish, we tried to describe the molecular details of the interaction using in vitro assays which we complement with in vivo mouse data. We describe that the primary lymphangiogenic factor VEGF-C is produced as an inactive precursor (pro-VEGF-C). Pro-VEGF-C (that is the 29/31-kDa-form) does bind to VEGFR-3 on endothelial cells, but is unable to activate it. Until now, the common wisdom was that pro-VEGF-C is only a less potent activator of VEGFR-3 than mature VEGF-C. In fact, it actually acts as a competitive inhibitor of mature VEGF-C. The task of CCBE1 is to assist the ADAMTS3 protease in cleaving cell-surface bound pro-VEGF-C and thus to localize the concentration of active VEGF-C. In hereditary diseases that are caused by mutations in CCBE1 ( Hennekam syndrome ), this activation of VEGF-C is impaired and causes lymphedema. Because of the importance of lymphatic vessels in many diseases, CCBE1 and ADAMTS3 are interesting drug targets. In cancer, for example, it would be a tremendous benefit if one could prevent the activation of VEGF-C and thus prevent VEGF-C-mediated metastasis.