The position will be for 2-years with the possibility of 3rd year extension

Starting date: February 2021

We seek to hire a highly motivated postdoctoral fellow to work on cellular and molecular mechanisms governing development of hidradenitis suppurativa (HS). HS is a chronic inflammatory dermatosis, affecting 1% of the population with no treatment so far. In the last years, our team has acquired extensive expertise in HS and provided a set of tools and data pointing to hair follicles stem cells (HF-SC) as key player in the HS physiopathology. Thanks to an optimized tissue culture system to isolate HF-SC from the outer root sheath of the hair follicle, we have shown:

  1. HF-SC isolated from HS patients displayed proinflammatory phenotype. Indeed, HF-SC from HS patients spontaneously secrete IP10 (CXCL10) and RANTES (CCL5).
  2. HF-SC isolated from HS patients displayed a replicative stress. Clonotypic characterization of HF-SC demonstrated an increased proliferative activity combined with progressive loss of quiescent stem cells. These cell homeostasis impairments led to DNA damage and were associated with replication stress, as demonstrated by alterations in replication fork progression and activation of the ATR-CHK1 pathway.
  3. Accumulation of single strand DNA and micronuclei in the cytosol of HF-SC isolated from HS patients was found to contribute to STING activation via the DNA sensor IFI16. STING pathway activation induce IFN type I production in HF-SC.

The aim of this project is to propose a novel and reliable classification of the HS disease founded on these recent pathophysiological features demonstrated by our team. The hypothesis behind this project relies on our recent demonstration that a subgroup of HS patients exhibited HF-SC defect with features of replicative stress abnormalities. This observation paves the way for identification of new epigenetic and genetic mechanisms responsible for these biological abnormalities. The post-doc will investigate genetic, epigenetic and transcriptomic signatures responsible for replicative stress in HS.

 

The postdoc candidate should have expertise in both cellular and molecular biology. Extensive knowledge in stem cell culture and routine molecular biology techniques is required. A background in single cell transcriptomics, both experimental procedure and bioinformatic analysis would be appreciated but not required. The post-doc candidate will integrate our team located at IMRB. IMRB is one of the major pluridisciplinary biomedical research centres in the eastern part of the Paris region. The research teams develop high-standing basic and translational research in a wide variety of fields in direct connection with healthcare services and a large number of patient cohorts. It comprises almost 600 people belonging to 14 research teams, and 4 technological platforms.

 

Selected publications of the host team relative to the project:

Orvain C, Lin YL, Jean-Louis F, …, Hüe S. Hair follicle stem cell replication stress drives IFI16/STING-dependent inflammation in hidradenitis suppurativa. J Clin Invest. 2020 Jul 1;130(7):3777-3790.

Hotz C, Boniotto M, … Hüe S. Intrinsic Defect in Keratinocyte Function Leads to Inflammation in Hidradenitis Suppurativa. J Invest Dermatol. 2016 Sep;136(9):1768-80.

Website: https://www.imrb.inserm.fr

Interested candidates should send their CV, a motivation letter including research interests and names of 2 referees to: sophie.hue@aphp.fr

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