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ZMOD SIGNED

Blood Vessel Development and Homeostasis: Identification and Functional Analysis of Genetic Modifiers

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EC-Contrib. €

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Partnership

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Project "ZMOD" data sheet

The following table provides information about the project.

Coordinator
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV 

Organization address
address: HOFGARTENSTRASSE 8
city: Munich
postcode: 80539
website: www.mpg.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Project website https://www.mpi-hlr.de/en/forschung/dept-iii/
 Total cost 2˙500˙000 €
 EC max contribution 2˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-AdG
 Funding Scheme ERC-ADG
 Starting year 2016
 Duration (year-month-day) from 2016-10-01   to  2021-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV DE (Munich) coordinator 2˙500˙000.00

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 Project objective

The vascular system is a complex network of blood vessels that transports gases, nutrients and hormones throughout the organism. Most blood vessels that form during development and growth arise by the sprouting of new capillaries from pre-existing vessels, a process termed angiogenesis. An imbalance in angiogenesis contributes to the pathogenesis of numerous disease states: insufficient angiogenesis limits tissue recovery in ischemic disease, whereas stimulation of angiogenesis by cancer cells promotes tumor vascularization and growth. Angiogenesis inhibitors are already in clinical use for anti-tumor therapy; however, multiple reports of resistance are calling for the identification of additional targets. Furthermore, vascular malformations are a significant cause of morbidity and mortality. While the genetic basis for some vascular malformations is known, many genetic factors, including modifiers that affect the age-of-onset and severity of phenotypes, remain to be identified. Identifying modifier genes is important not only to fully assess genetic risk, but also to provide novel targets for therapy; however, identifying modifier genes has proven challenging. We recently uncovered a novel and simple way to identify modifier genes. By investigating gene and protein expression differences between knockout (mutant) and knockdown (antisense treated) zebrafish embryos, we found that mutations in specific genes, including some encoding angiogenic factors, lead to the upregulation of compensating (i.e., modifier) genes while knocking down these same genes does not. We hypothesize that the modifier genes identified through this approach in zebrafish also play important roles in humans. Thus, we will use this simple strategy to identify new genes that regulate vascular formation and homeostasis, and subsequently analyze their function in zebrafish as well as in mammalian models, as they are likely to play key roles in vascular development and disease.

 Publications

year authors and title journal last update
List of publications.
2019 Shih-Lei Lai, Rubén Marín-Juez, Didier Y. R. Stainier
Immune responses in cardiac repair and regeneration: a comparative point of view
published pages: 1365-1380, ISSN: 1420-682X, DOI: 10.1007/s00018-018-2995-5
Cellular and Molecular Life Sciences 76/7 2019-09-04
2019 Mohamed A. El-Brolosy, Zacharias Kontarakis, Andrea Rossi, Carsten Kuenne, Stefan Günther, Nana Fukuda, Khrievono Kikhi, Giulia L. M. Boezio, Carter M. Takacs, Shih-Lei Lai, Ryuichi Fukuda, Claudia Gerri, Antonio J. Giraldez, Didier Y. R. Stainier
Genetic compensation triggered by mutant mRNA degradation
published pages: 193-197, ISSN: 0028-0836, DOI: 10.1038/s41586-019-1064-z
Nature 568/7751 2019-09-04
2019 Jason K.H. Lai, Kristina K. Gagalova, Carsten Kuenne, Mohamed A. El-Brolosy, Didier Y.R. Stainier
Induction of interferon-stimulated genes and cellular stress pathways by morpholinos in zebrafish
published pages: , ISSN: 0012-1606, DOI: 10.1016/j.ydbio.2019.06.008
Developmental Biology 2019-09-04
2017 Claudia Gerri, Rubén Marín-Juez, Michele Marass, Alora Marks, Hans-Martin Maischein, Didier Y R. Stainier
Hif-1α regulates macrophage-endothelial interactions during blood vessel development in zebrafish
published pages: , ISSN: 2041-1723, DOI: 10.1038/ncomms15492
Nature Communications 8/1 2019-07-09
2018 Ryota L. Matsuoka, Didier Y.R. Stainier
Recent insights into vascular development from studies in zebrafish
published pages: 1, ISSN: 1065-6251, DOI: 10.1097/moh.0000000000000420
Current Opinion in Hematology 2019-09-04
2017 Benjamin E. Housden, Matthias Muhar, Matthew Gemberling, Charles A. Gersbach, Didier Y. R. Stainier, Geraldine Seydoux, Stephanie E. Mohr, Johannes Zuber, Norbert Perrimon
Loss-of-function genetic tools for animal models: cross-species and cross-platform differences
published pages: 24-40, ISSN: 1471-0056, DOI: 10.1038/nrg.2016.118
Nature Reviews Genetics 18/1 2019-07-09
2017 Simon Lalonde, Oliver A. Stone, Samuel Lessard, Adam Lavertu, Jessica Desjardins, Mélissa Beaudoin, Manuel Rivas, Didier Y. R. Stainier, Guillaume Lettre
Frameshift indels introduced by genome editing can lead to in-frame exon skipping
published pages: e0178700, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0178700
PLOS ONE 12/6 2019-07-09
2017 Thomas Braun, Stefan Offermanns, Didier Y.R. Stainier, Werner Seeger
The Max Planck Institute for Heart and Lung Research Curiosity-Driven Basic Research to Fight Cardio-Pulmonary Diseases
published pages: 1386-1389, ISSN: 0009-7330, DOI: 10.1161/circresaha.117.310763
Circulation Research 120/9 2019-09-04
2017 Benjamin E. Housden, Matthias Muhar, Matthew Gemberling, Charles A. Gersbach, Didier Y. R. Stainier, Geraldine Seydoux, Stephanie E. Mohr, Johannes Zuber, Norbert Perrimon
Loss-of-function genetic tools for animal models: cross-species and cross-platform differences
published pages: 24-40, ISSN: 1471-0056, DOI: 10.1038/nrg.2016.118
Nature Reviews Genetics 18/1 2019-09-04
2017 Mohamed A. El-Brolosy, Didier Y. R. Stainier
Genetic compensation: A phenomenon in search of mechanisms
published pages: e1006780, ISSN: 1553-7404, DOI: 10.1371/journal.pgen.1006780
PLOS Genetics 13/7 2019-06-13

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