CCBE1 on Michael’s Domain

VEGF-C Review in Frontiers in Bioengineering and Biotechnology

Mon, 12 Feb 2018 00:00:00 +0000

The editors of Frontiers in Bioengineering and Biotechnology, section Tissue Engineering and Regenerative Medicine (Andrea Banfi, Wolfgang Holnthoner, Mikaël M. Martino and Seppo Ylä-Herttuala) asked us to contribute to the research topic Vascularization for Regenerative Medicine. We wrote a small review about VEGF-C, which specifically addresses the molecular biology of VEGF-C in relationship to regenerative medicine, i.e., (re)growing lymphatic vessels in vitro or in vivo.You can get it from the publisher directly https://www.frontiersin.org/articles/10.3389/fbioe.2018.00007/full or from here . **UPDATE (April 1, 2023):**The question of whether Frontiers Media is a predatory publisher did not even cross our minds when we were asked to contribute with a review. I know the guest editors of this Research Topic and can vouch for their scientific integrity. However, the journal has recently ended up on the list of predatory journals ( https://predatoryreports.org/news/f/list-of-all-frontiers-media-predatory-journals ), and the issues are discussed here in detail. Our review has meanwhile gathered:

Science good, coffee bad

Thu, 26 Jan 2017 00:00:00 +0000

Last week I took part the Vascular Cell Biology Gordon Research Conference in Ventura (California). My two previous Gordon Conferences (2001 Rhode Island, 2014 Lucca/Italy) were outstanding and also this one did not disappoint.Even though there were many European researchers (19%), the US made up for 69% of the participants (Asia 6%, rest of the Amerikas 5%). This is probably a good representation of where the cutting edge research in vascular biology happens. Makes me wonder why the coffee in the US is as bad as it is (my bias got confirmed again). It cannot be explained by the lack of scientific expertise.Gordon conferences are designed to promote the exchange of unpublished data and hence I am not writing anything about the science. One exception: There are clinical trials to treat lymphedema with leukotriene B4 inhibitors ), but this is already public knowledge and the mouse studies are mostly published ( http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0008380) . So no secrets leaked here… I myself presented a poster about the continued CCBE1 story that is currently under review and some preliminary data about additional VEGF-C activating enzymes.Obviously, the outcome of the presidential elections was a popular topic during lunch and dinner conversations especially as it relates to science funding and science policy. Opinions ranged from “We have no clue what to expect” to “Be afraid. Be very afraid.” I personally enjoyed about 8 hours of Trump presidency since my return flight from Los Angeles to Munich left last Friday at a quarter past five in the afternoon.In the free afternoons, I tried to catch the America-exclusive Taurus Pokémon for my daughter Milena. Sadly, the conference location was almost entirely devoid of poke stops and therfore I was chronically short of poke balls. Insiders told me that Santa Monica beach is the place to go to in order to catch Pokémons. I actually planned to go there Friday morning, but it was raining cats and dogs and so I tried my luck at the airport and about an hour before departure I finally managed to catch a Taurus and another one just before boarding the plane. So all in all a very successful conference journey!

Lymphangiogenesis in health and disease

Thu, 11 Jun 2015 00:00:00 +0000

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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.

From the molecular biological foundations to causal treatment options for diseases of the lymphatic system

Tue, 22 Jul 2014 00:00:00 +0000

PD Dr Michael Jeltsch, University of Helsinki, Finland

Research into the molecular basis of lymphangiogenesis in embryonic development and pathological processes has led to a rapid expansion of our knowledge (Krebs and Jeltsch 2013a, 2013b). The molecular biology era of lymphatic research began with the discovery of VEGF growth factors and their receptors 25 years ago. This review therefore focuses on these molecules.

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.