Extracellular vesicle–mediated transmission of ER stress and mitochondrial dysfunction in liver fibrosis

Metabolic dysfunction–associated steatohepatitis is a leading cause of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Hepatocyte injury initiates fibrogenesis, yet how stressed hepatocytes transmit pathogenic signals to neighboring cells remains poorly understood.

Work from Dr Bailly-Maitre’s team shows that hepatocyte-specific inhibition of IRE1α RNase activity protects against liver fibrosis (Hazari et al, Hepatology 2026). In parallel, our data indicate that ER-stress components are released in the hepatocyte secretome and transferred to hepatocytes and hepatic stellate cells, promoting disease progression. Emerging evidence from Dr Chami’s laboratory gain expertise in extracellular vesicles (EVs) studies in Alzheimer’s disease (Lauritzen et al., J Extracellular Vesicles 2025; Eysert et al., DOI: https://doi.org/10.1101/2025.01.08.631851). They demonstrate that stressed cells export dysfunctional mitochondria through large EVs containing mitochondria, propagating metabolic stress between cells. They develop reliable protocols for small and large EVs isolation from tissues in vivo. 

This PhD project will test whether hepatocyte-derived EVs act as vectors of ER-stress signals and mitochondrial dysfunction, thereby amplifying fibrogenesis. Using genetically engineered mouse models targeting hepatocyte IRE1αRNase activity, combined with EVs isolation and proteomic characterization, mitochondrial transfer assays, and metabolic profiling, we will define how EVs cargo reprograms recipient hepatocytes and HSCs.

The project relies on a complementary collaboration between a team specialized in liver biology, ER stress and fibrosis and a team expert in EVs and mitochondrial biology. Beyond liver pathology, we will explore whether chronic hepatocyte stress and EV-mediated mitochondrial dissemination contribute to cognitive alterations, building on Dr Chami’s expertise in neurodegenerative diseases and data linking hepatocyte RNase activity to systemic inflammation.

www.c3m-nice.fr/equipes/equipe-13/

https://www.ipmc.cnrs.fr/fr/member/mounia-chami/

Nous recherchons :

un(e) étudiant(e) actuellement en Master 2 (promotion 2026),
ou un(e) diplômé(e) de Master 2 promotion 2025, idéalement obtenu avec mention.

une mention au Master 1 sera particulièrement appréciée.

Les candidatures nationales et internationales sont les bienvenues.

Le laboratoire bénéficie d’une forte ouverture internationale. La thèse pourra inclure un séjour de recherche d’environ un mois dans un laboratoire d’excellence partenaire, en lien avec le projet — par exemple au Chili, dans le cadre d’un programme d’échange scientifique international.

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Candidate Profile

We are seeking:

a current Master’s student (M2 – class of 2026),
or a Master’s graduate from the class of 2025, ideally with distinction.

A strong academic record during the Master’s program (M1 and M2) will be particularly appreciated.

National and international applications are welcome.

Our laboratory has a strong international outlook, and the PhD project may include a research stay of approximately one month in a leading partner laboratory related to the project — for example in Chile — through an international scientific exchange program.