Project

Investigating the function and development of ‘lipid-associated macrophages’ (LAMs) in liver fibrosis across species.

Code
3F017421
Duration
01 November 2021 → 31 October 2023
Funding
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Single-cell data analysis
    • Metabolic diseases
    • Hepatology
    • Inflammation
    • Innate immunity
Keywords
Macrophage involvement in the development and progression of liver fibrosis Specific functions of resident versus recruited macrophages in liver disease Conserved features of recruited liver macrophages across species
 
Project description

Hepatic macrophages are thought to play key roles in the development and progression of fatty liver disease (MAFLD) and liver fibrosis. However, in recent years it has become clear that both the fatty and the fibrotic liver are home to a number of distinct macrophage subsets, whose precise roles in disease pathogenesis have not yet been assessed. This includes a population of recruited macrophages in the murine and human fatty liver termed lipid associated macrophages (LAMs). A similar population has also been identified in fibrotic livers in the absence of obesity. While LAM abundance and protein expression correlates with disease severity suggesting a pathogenic function of these cells, the precise roles played by LAMs remain to be studied. Gaining a better understanding of the roles played by these cells in liver disease, could ultimately lead to the identification of novel therapeutic strategies. To this end, here I will take a 3-pronged approach to understand hepatic LAM function. Firstly, using single cell technologies I will identify conserved and unique features of LAMs across disease models and species. Using genetically modified mouse models, I then will investigate the specific functions of these cells. Finally, using spatial transcriptomics, I will assess the cell-cell communication and specific signals driving LAM development and maintenance with the ultimate aim of being able to manipulate the generation of LAMs in the clinic to improve patient health.