PhD candidate (M/F) in microfluidic bioengineering: functional modeling of a liver sinusoid on a chip

Job Description

Thesis Subject

Metabolic dysfunction–associated steatotic liver disease (MASLD) is a major public health issue, affecting approximately 32% of the global population. It begins with an accumulation of fat in the liver (steatosis) and is closely linked to metabolic syndrome. In about 20% of cases, it progresses to an inflammatory form called MASH. This progression can lead to severe complications such as cirrhosis or hepatocellular carcinoma. These advanced diseases are responsible for approximately 2 million deaths per year. The mechanisms underlying MASLD progression are complex and multifactorial. They have long been studied primarily at the level of hepatocytes. However, liver sinusoidal endothelial cells (LSECs) play a key role. These cells normally maintain vascular homeostasis and limit inflammation and fibrosis. From the early stages of the disease, they lose these protective functions. This alteration leads to a decrease in nitric oxide (NO) production. It also promotes the activation of hepatic stellate cells (HSCs). This contributes to an increase in intrahepatic vascular resistance (IHVR). This phenomenon appears even before inflammation or fibrosis. IHVR results both from sinusoidal compression and endothelial dysfunction. Interactions between LSECs and HSCs are then profoundly disrupted. Current therapeutic options for MASH remain limited. This project proposes to develop a liver sinusoid-on-a-chip model. This microphysiological system will integrate the effects of flow and inflammatory mediators.
It will make it possible to faithfully reproduce the alterations observed in MASLD. This model will be used to study the mechanisms of the disease, evaluate existing drugs, identify new biomarkers, and support the development of new therapeutic strategies.

Your Work Environment

This PhD project will be hosted within the team Dynamic and multi-scale processes of spontaneous organization in tissue morphogenesis, led by Dr. Wenjin Xiao at the Dev2A laboratory (UMR 8263), IBPS, Sorbonne University. The team has recognized expertise in the development of microfluidic models adapted to applications, integrating relevant mechanical conditions such as fluid flow and substrate viscoelasticity. The work will be carried out under the supervision of Dr. Valérie Bello and co-supervised by Dr. Wenjin Xiao. The research will be conducted primarily at Dev2A, with occasional activities at ICAN-Human Liver Biology, Hôpital de la Pitié-Salpêtrière, Sorbonne University. The activities will be occasionally carried out at the Centre de recherche sur l'inflammation, Hôpital Bichat, Université Paris Cité.

Constraints and risks

No constraints or risks to declare.

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

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