HDR Defense: Lætitia SEGUIN

« Communication cellule-matrice extracellulaire : un facteur clé dans la différenciation et la transformation des progéniteurs pulmonaires  » 

 Abstract : My research work aims to better understand the mechanisms that link lung regeneration and tumorigenesis, particularly in lung adenocarcinoma (LUAD). The lung is organized into distinct anatomical compartments, including the bronchioles and alveoli, which host specific populations of progenitor cells capable of contributing to epithelial repair after injury and potentially constituting the origin of lung tumors. The objective of this work is to explore how the tissue microenvironment modulates the behavior of these progenitor cells, influencing their regenerative capacity, plasticity, and susceptibility to oncogenic transformation. A better understanding of these interactions should make it possible to identify the mechanisms that guide repair either towards effective regeneration or, conversely, towards pathological evolution. A second axis of this research aims to determine how these mechanisms are modified during the lung repair process and how they can be altered in pathological contexts such as pulmonary fibrosis. Finally, this research program is interested in the impact of aging on these processes. Age-related changes profoundly affect the structure and function of the lung and could remodel the dynamics of progenitor cells, as well as their contribution to regeneration and tumorigenesis. Overall, this work seeks to better understand how cell identity and the lung microenvironment contribute to the heterogeneity of lung cancers and tissue repair mechanisms, in order to open up new therapeutic perspectives in oncology and regenerative medicine.