EMERGE SIGNED
Epigenetic and metabolic regulation of endothelial heterogeneity
Total Cost €
0EC-Contrib. €
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Project "EMERGE" data sheet
The following table provides information about the project.
| Coordinator |
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Organization address contact info |
| Coordinator Country | Germany [DE] |
| Project website | https://www.angio-met-lab.com |
| Total cost | 1˙998˙750 € |
| EC max contribution | 1˙998˙750 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2017-COG |
| Funding Scheme | ERC-COG |
| Starting year | 2018 |
| Duration (year-month-day) | from 2018-03-01 to 2023-02-28 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV | DE (Munich) | coordinator | 1˙998˙750.00 |
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Project objective
Heterogeneity within the endothelium is increasingly recognized in both normal and disease conditions, influencing vascular architecture, structure, and function. The diverse phenotypes that endothelial cells (ECs) adopt suggest substantial plasticity and indicate that heterogeneity is a core property that enables ECs to fulfill their tissue-specific tasks. However, the molecular basis for tissue-specific endothelial differentiation and heterogeneity remains largely unknown. In this project, we will study the impact of environmental context on endothelial specialization and focus on the emerging relationship between metabolism, epigenetics, and cellular differentiation. We hypothesize that organ-specific differences in endothelial metabolic state, through altered epigenetics, promote specialization and thereby contribute to heterogeneity within the vascular system. The proposal rests on the notion that many of the enzymes that erase epigenetic modifications (from DNA and histones) are exquisitely sensitive to changes in metabolism as they utilize cosubstrates that are generated by cellular metabolism. Using a combination of state-of-the-art genetics, high-resolution imaging, metabolomics, and biochemistry, we will study the role of these epigenetic mechanisms for general and organ-specific blood vessel formation (Objective I) and determine their regulation by metabolic and vascular differentiation signals (Objective II). Moreover, we will explore whether metabolic changes during obesity and aging impact the maintenance of endothelial specialization, and assess whether deregulation of metabolic-epigenetic signalling leads to endothelial malfunction and organ failure (Objective III). We trust that the knowledge gained through this project will provide a conceptual framework for understanding how environmental context can drive vascular heterogeneity and, more generally, how alterations in metabolism and nutrition might contribute to vascular-related diseases.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2019 |
Lim R, Sugino T, Nolte H, Andrade J, Zimmermann B, Shi C, Doddaballapur A, Ong YT, Wilhelm K, Fasse JWD, Ernst A, Kaulich M, Husnjak K, Boettger T, Guenther S, Braun T, Krüger M, Benedito R, Dikic I, Potente M Deubiquitinase USP10 regulates Notch signaling in the endothelium published pages: 364(6436):188-19, ISSN: 0036-8075, DOI: |
Science | 2019-10-30 |
| 2018 |
Meghan Riddell, Akiko Nakayama, Takao Hikita, Fatemeh Mirzapourshafiyi, Takuji Kawamura, Ayesha Pasha, Mengnan Li, Mikio Masuzawa, Mario Looso, Tim Steinbacher, Klaus Ebnet, Michael Potente, Tomonori Hirose, Shigeo Ohno, Ingrid Fleming, Stefan Gattenlöhner, Phyu P. Aung, Thuy Phung, Osamu Yamasaki, Teruki Yanagi, Hiroshi Umemura, Masanori Nakayama aPKC controls endothelial growth by modulating c-Myc via FoxO1 DNA-binding ability published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-07739-0 |
Nature Communications 9/1 | 2019-10-30 |
| 2018 |
Radiance Lim, Michael Potente Top-NOTCH Regulation of Cardiac Metabolism published pages: 2609-2612, ISSN: 0009-7322, DOI: 10.1161/circulationaha.118.033669 |
Circulation 137/24 | 2019-10-30 |
| 2019 |
Jorge Andrade, Michael Potente Endothelial metabolism—more complex (III) than previously thought published pages: , ISSN: 2522-5812, DOI: |
Nature Metabolism | 2019-10-30 |
| 2018 |
Oliver A. Stone, Mohamed El-Brolosy, Kerstin Wilhelm, Xiaojing Liu, Ana M. Romão, Elisabetta Grillo, Jason K. H. Lai, Stefan Günther, Sylvia Jeratsch, Carsten Kuenne, I-Ching Lee, Thomas Braun, Massimo M. Santoro, Jason W. Locasale, Michael Potente, Didier Y. R. Stainier Loss of pyruvate kinase M2 limits growth and triggers innate immune signaling in endothelial cells published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-06406-8 |
Nature Communications 9/1 | 2019-10-30 |
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