PhD Position INSERM UMR1149 Pathophysiology and Treatment of Viral Hepatitis
Summary of the project
Title: From the immune liver microenvironment during chronic hepatitis B to the mechanisms of liver fibrosis progression
Keywords: Chronic hepatitis B, Fibrosis, Immune micro-environment, Inflammation, Antigen-specific T cells
Abstract :
Hepatitis B virus (HBV) infection is a major risk factor for hepatitis, liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Inflammation plays an important role in viral clearance, but excessive or inadequate inflammation can cause liver damages and may accelerate fibrosis progression and HCC development. Chronic HBV infection (HBC) causes dysfunction of innate and adaptive immune responses involving monocytes/macrophages, dendritic cells (DC), natural killer (NK) cells, B cells and T cells. However, the mechanisms that link HBV-induced immune alterations and hepatic damages remain poorly understood. In this project, we aim to study the immune microenvironment in different conspicuous and homogeneous groups of CHB patients, belonging to different stages of fibrosis, and as compared to healthy individuals. Using the cutting-edge multiplex immunofluorescence technology (CODEX), we will analyze the in situ distribution, localization and cell-cell interaction of key immune cell subsets as well as their associated antiviral responses. In a mechanistic approach, we will study the functional profile of HBV-specific T cells in their capacity to generate cytotoxic responses and to produce pro- and anti-fibrotic cytokines in response to cognate antigen stimulation. Altogether, this research program may unravel novel biological mechanisms associated with fibrosis progression as well as potential prognosis biomarkers and new therapeutic targets.
Contact:
Tarik Asselah, MD, PhD,
Professor of Medicine, Université de Paris; Hepatology Department, Hôpital Beaujon;
Head of Viral HepatitisTeam,INSERM UMR1149, Pathophysiology and Treatment of Viral Hepatitis,
Laboratory of Excellence Labex INFLAMEX,
Address: Hôpital Beaujon, Pavillon Abrami, 100 Bd du Général Leclerc, 92110 Clichy, France
Phone : +33(0)660957890
email : tarik.asselah@aphp.fr