Lung Thrombopoïesis: Regulation and Function in Lung Inflammation
Project Description:
We have recently demonstrated that extramedullar thrombopoiesis occurs in the lung but the specificities, regulation and significance of this local production is unknown. Recent studies and our preliminary data suggest that lung megakaryocytes have a specific role in inflammation and that platelet biology are altered during lung damage by local inflammatory mediators, including by the tissue alarmins.
This PhD project aims at studying lung thrombopoieisis regulation and specificities and evaluate the impact of lung platelet modifications on hyper inflammation and remodeling. The project integrates the use of murine models of lung inflammation, flow cytometry, proteomic analysis and cutting edge lung intravital microscopy. The overall goal is to bring a deeper understanding of lung inflammatory diseases where platelets are known to contribute to dysregulated inflammation (ARDS, asthma, COPD, viral infection…) and will support the discovery of new therapeutic targets. The project will be advised by Emma Lefrançais in the lab of Jean-Philippe Girard
- Lefrançais E et al. The lung is a site of platelet biogenesis and a reservoir for megakaryocytes and hematopoietic progenitors. Nature 2017
- Lefrançais E and Looney M "Platelet biogenesis in lung circulation" Physiology 2019. 34 (6) 392-401
- Cayrol C et al Environmental allergens induce allergic inflammation through proteolytic maturation of IL-33 Nature Immunology 2018
- Cayrol C, Girard JP. Interleukin-33 (IL-33): A nuclear cytokine from the IL-1 family. Immunol Rev. 2018
- Liew FY, Girard JP, Turnquist HR. Interleukin-33 in health and disease. Nature Reviews Immunology 2016
- Lefrançais E et al. The central domain of IL-33 is cleaved by mast cell proteases for potent activation of group 2 innate lymphoid cells. PNAS 2014
We are looking for:
- creative and highly motivated Ph.D. students of all nationalities strongly committed to research
- applicants must have an excellent M.Sc. or equivalent degree with a strong background in immunology and/or physiopathology
- Experience in flow cytometry and in vivo models will be a plus.
Interested in joining us?
To apply, please email a cover letter, complete CV and references to Emma.Lefrancais@ipbs.fr