Vessel Formation in Development and Disease Group

K.D. Wagner

Institut de Biologie Valrose, iBV

CNRS UMR7277 – Inserm U1091

Université Nice Sophia Antipolis

Parc Valrose

06108 Cedex 2

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 .

Contacts: Kay-Dietrich Wagner – kwagner@unice.fr

Nicole Wagner – nwagner@unice.fr

Eligibility