Vessel formation in development and disease

Main interests

  • cardiovascular development
  • regeneration
  • cancer and tumour stroma cell interaction
  • angiogenesis

Scientific Questions

The primary interest of our research is to understand how vessels grow and re-model. As besides endothelial cells, different cell types, e.g. hematopoietic progenitor and myeloid derived cells, pericytes, and smooth muscle cells are involved in vessel formation and maturation, we are interested in the contribution of these different cell types for vessel formation under physiological and pathological conditions. Furthermore, we want to identify signals from surrounding tissues, e.g. myocardium, tumour stroma and immune cells, which modify vessel growth. Finally, the aim of our projects is to translate our findings into potential novel therapeutic approaches and to identify new  pharmacological candidates to modify vascular growth.

Our Strategy

The cardiovascular system is the first functional organ system required for embryonic survival. Many major diseases and pathophysiological processes are associated with vessel formation, e.g. coronary artery disease, peripheral arterial diseases, liver fibrosis, wound healing, graft rejection, or cancer. Chronic ischemic heart disease, myocardial infarction, and cancer are the most common causes for morbidity and mortality. In ischemic heart disease, angiogenesis is required for collateral vessel formation and therefore a “friend”, in cancer it becomes a “foe” by inducing the transition of a tumour from a small cluster of malignant cells to a macroscopic tumour capable of spreading to other organs via the vasculature.

We use mainly analyses in mice in vivo (reporter and lineage tracing strains, inducible knockout / overexpression / knockin mice).

The in vivo data are supported by cell culture systems and molecular approaches. We use CRISPR/Cas9 technology to generate reporter cell lines, which serve to test small molecule libraries for their potential to inhibit / activate genes of interest.

Research Aims

Characterization of different cell types contributing to tumour angiogenesis and progression.

Identification of proteins critically involved in cardiac angiogenesis and repair.

Discovery of new small molecules to modify vascular formation.


WAGNER Nicole - +33 489153713

Clinical Researchers

LECCIA Nathalie - +33 493377665
CHAU Yves - +33 A


  1. Wagner, N, Wagner, KD. Recent Insights into the Role of PPARs in Disease. Cells. 2023;12 (12):. doi: 10.3390/cells12121572. PubMed PMID:37371042 PubMed Central PMC10296837.
  2. Wagner, N, Wagner, KD. Molecular Mechanisms of Cardiac Development and Disease. Int J Mol Sci. 2023;24 (10):. doi: 10.3390/ijms24108784. PubMed PMID:37240127 PubMed Central PMC10218175.
  3. Díaz Del Moral, S, Benaouicha, M, Villa Del Campo, C, Torres, M, Wagner, N, Wagner, KD et al.. Cardiomyocyte-Specific Wt1 Is Involved in Cardiac Metabolism and Response to Damage. J Cardiovasc Dev Dis. 2023;10 (5):. doi: 10.3390/jcdd10050211. PubMed PMID:37233178 PubMed Central PMC10219250.
  4. Wagner, N, Wagner, KD. Controversies and Recent Advances in Senescence and Aging. Cells. 2023;12 (6):. doi: 10.3390/cells12060902. PubMed PMID:36980243 PubMed Central PMC10046983.
  5. Wagner, N, Wagner, KD. Pharmacological Utility of PPAR Modulation for Angiogenesis in Cardiovascular Disease. Int J Mol Sci. 2023;24 (3):. doi: 10.3390/ijms24032345. PubMed PMID:36768666 PubMed Central PMC9916802.
  6. Wagner, KD. Editorial (Preface) "Cells/Cells of the Cardiovascular System-Editorial Highlights 2020-2021: The Book Selection". Cells. 2022;11 (23):. doi: 10.3390/cells11233898. PubMed PMID:36497157 PubMed Central PMC9735509.
  7. Safwan-Zaiter, H, Wagner, N, Wagner, KD. P16INK4A-More Than a Senescence Marker. Life (Basel). 2022;12 (9):. doi: 10.3390/life12091332. PubMed PMID:36143369 PubMed Central PMC9501954.
  8. Wagner, N, Wagner, KD. Peroxisome Proliferator-Activated Receptors and the Hallmarks of Cancer. Cells. 2022;11 (15):. doi: 10.3390/cells11152432. PubMed PMID:35954274 PubMed Central PMC9368267.
  9. Wagner, KD. The Editor's Choice Articles-Section "Cells of the Cardiovascular System" 2020-2021. Cells. 2022;11 (14):. doi: 10.3390/cells11142173. PubMed PMID:35883616 PubMed Central PMC9323559.
  10. Wagner, KD, Wagner, N. The Senescence Markers p16INK4A, p14ARF/p19ARF, and p21 in Organ Development and Homeostasis. Cells. 2022;11 (12):. doi: 10.3390/cells11121966. PubMed PMID:35741095 PubMed Central PMC9221567.
  11. Wagner, N, Wagner, KD. Transcriptional Regulation of Cardiac Development and Disease. Int J Mol Sci. 2022;23 (6):. doi: 10.3390/ijms23062945. PubMed PMID:35328365 PubMed Central PMC8953235.
  12. Safwan-Zaiter, H, Wagner, N, Michiels, JF, Wagner, KD. Dynamic Spatiotemporal Expression Pattern of the Senescence-Associated Factor p16Ink4a in Development and Aging. Cells. 2022;11 (3):. doi: 10.3390/cells11030541. PubMed PMID:35159350 PubMed Central PMC8833900.
  13. Wagner, N, Wagner, KD. Every Beat You Take-The Wilms' Tumor Suppressor WT1 and the Heart. Int J Mol Sci. 2021;22 (14):. doi: 10.3390/ijms22147675. PubMed PMID:34299295 PubMed Central PMC8306835.
  14. Wagner, N, Ninkov, M, Vukolic, A, Cubukcuoglu Deniz, G, Rassoulzadegan, M, Michiels, JF et al.. Implications of the Wilms' Tumor Suppressor Wt1 in Cardiomyocyte Differentiation. Int J Mol Sci. 2021;22 (9):. doi: 10.3390/ijms22094346. PubMed PMID:33919406 PubMed Central PMC8122684.
  15. Ghanbarian, H, Aghamiri, S, Eftekhary, M, Wagner, N, Wagner, KD. Small Activating RNAs: Towards the Development of New Therapeutic Agents and Clinical Treatments. Cells. 2021;10 (3):. doi: 10.3390/cells10030591. PubMed PMID:33800164 PubMed Central PMC8001863.
  16. Wagner, KD, Wagner, N. PPARs and Myocardial Infarction. Int J Mol Sci. 2020;21 (24):. doi: 10.3390/ijms21249436. PubMed PMID:33322384 PubMed Central PMC7764190.
  17. Wagner, N, Wagner, KD. The Role of PPARs in Disease. Cells. 2020;9 (11):. doi: 10.3390/cells9112367. PubMed PMID:33126411 PubMed Central PMC7692109.
  18. Belali, T, Wodi, C, Clark, B, Cheung, MK, Craig, TJ, Wheway, G et al.. WT1 activates transcription of the splice factor kinase SRPK1 gene in PC3 and K562 cancer cells in the absence of corepressor BASP1. Biochim Biophys Acta Gene Regul Mech. 2020;1863 (12):194642. doi: 10.1016/j.bbagrm.2020.194642. PubMed PMID:33017668 .
  19. Du, S, Wagner, N, Wagner, KD. The Emerging Role of PPAR Beta/Delta in Tumor Angiogenesis. PPAR Res. 2020;2020 :3608315. doi: 10.1155/2020/3608315. PubMed PMID:32855630 PubMed Central PMC7443046.
  20. Wagner, N, Wagner, KD. PPARs and Angiogenesis-Implications in Pathology. Int J Mol Sci. 2020;21 (16):. doi: 10.3390/ijms21165723. PubMed PMID:32785018 PubMed Central PMC7461101.
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An ANR funded PhD position is available in the Vessel Formation in Development and Disease group at the iBV

The role of p16-dependent cellular senescence in healthy aging


Description :

Cellular senescence attracts attention as a key player contributing to organismal aging. The accumulation of senescent cells is dramatically increased with aging, however their precise contribution to aging-related phenotypes remains largely unclear. In collaboration with the team of D. Bulavin we showed p16-dependent senescent cells are required for healthy aging. We used different novel inducible mouse lines to characterise the role of p16 expressing cells in different organs. Currently, we focussed mainly on liver. The project aims at identifying the cell repertoire linked to aging-induced senescence and to investigate the impact of senescent cells on liver functions and to understand molecular pathways modulated by senescence. For these purposes we will use p16-Cre and p16-Cre-ERT2 mice crossed either with Rosa26-mTmG reporter or Rosa26-DTA ablator mice. The animals will be investigated by histological and immunohistological methods and RNA sequencing will be performed at different ages. This project will help to understand the molecular mechanism responsible for aging-induced activation of senescence and hopefully identify potential molecular targets to manipulate senescence through reprogramming and/or selective elimination of subsets of senescent cells.

Required Skills :        

The working language is English.
Experience in molecular biology, cellular biology and/or mouse genetics would be a plus.
Motivation to work with mouse models and team orientation are required. Animal experimentation training is part of the project.

Related publications:

Grosse, L, Wagner, N, Emelyanov, A, Molina, C, Lacas-Gervais, S, Wagner, KD et al.. Defined p16High Senescent Cell Types Are Indispensable for Mouse Healthspan. Cell Metab. 2020:. doi: 10.1016/j.cmet.2020.05.002. PubMed PMID:32485135 .

Wagner, KD, Du, S, Martin, L, Leccia, N, Michiels, JF, Wagner, N et al.. Vascular PPARβ/δ Promotes Tumor Angiogenesis and Progression. Cells. 2019;8 (12):. doi: 10.3390/cells8121623. PubMed PMID:31842402 PubMed Central PMC6952835.

Wagner, KD, El Maï, M, Ladomery, M, Belali, T, Leccia, N, Michiels, JF et al.. Altered VEGF Splicing Isoform Balance in Tumor Endothelium Involves Activation of Splicing Factors Srpk1 and Srsf1 by the Wilms' Tumor Suppressor Wt1. Cells. 2019;8 (1):. doi: 10.3390/cells8010041. PubMed PMID:30641926 PubMed Central PMC6356959.

Wagner, KD, Ying, Y, Leong, W, Jiang, J, Hu, X, Chen, Y et al.. The differential spatiotemporal expression pattern of shelterin genes throughout lifespan. Aging (Albany NY). 2017;9 (4):1219-1232. doi: 10.18632/aging.101223. PubMed PMID:28437249 PubMed Central PMC5425123.

Wagner, KD, Cherfils-Vicini, J, Hosen, N, Hohenstein, P, Gilson, E, Hastie, ND et al.. The Wilms' tumour suppressor Wt1 is a major regulator of tumour angiogenesis and progression. Nat Commun. 2014;5 :5852. doi: 10.1038/ncomms6852. PubMed PMID:25510679 .

El Maï, M, Wagner, KD, Michiels, JF, Ambrosetti, D, Borderie, A, Destree, S et al.. The Telomeric Protein TRF2 Regulates Angiogenesis by Binding and Activating the PDGFRβ Promoter. Cell Rep. 2014;9 (3):1047-60. doi: 10.1016/j.celrep.2014.09.038. PubMed PMID:25437559 .


Kay-Dietrich Wagner – kwagner@unice.fr
Nicole Wagner – nwagner@unice.fr


2015 - Grand Prize in Cancerology from the Simone and Cino del Duca Foundation - French Academy of Sciences

2008 - Du Bois-Reymond-Prize - German Physiological Society

2007 - AVENIR - Inserm

2003 - Long-term Fellow - EMBO

1998 - Robert-Koch-Prize, Charité, Germany

Nicole Wagner, iBV researcher, presented the promises of cancer immunotherapy – The Evening of Hope, Monaco. October, 16th 2018

Cancer immunotherapy is a major approach to fight cancer. Nicole Wagner, Inserm Researcher at iBV, presented the promises and outcomes ...
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iBV - Institut de Biologie Valrose

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Université Nice Sophia Antipolis
Faculté de médecine
28 Avenue de Valombrose
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