Lipid Metabolism, MASLD & MASH-HCC Laboratory

(Head: Prof Michele Vacca)

Our laboratory is dedicated to uncovering the molecular mechanisms that drive the development and progression of Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) and its more advanced form, Metabolic dysfunction-Associated Steatohepatitis (MASH), including progression to hepatocellular carcinoma (HCC) and cardiovascular disease (CVD).

Research Focus

We aim to understand:

• The cellular and molecular drivers of MASLD onset and progression;
• The increased incidence of HCC and CVD in the context of obesity and MASLD.

Key Research Questions

1. What systemic factors regulate hepatic lipid metabolism and influence MASLD and MASH progression?
   We focus particularly on the crosstalk between adipose tissue and the liver, as well as the role of lipoproteins in these processes.
2. How does lipotoxicity trigger wound-healing responses that promote MASH progression and HCC?
   We investigate novel metabolic and signalling pathways that connect lipid-induced liver damage (lipotoxicity) to fibrogenic and oncogenic processes.

Our Research Strategy

We adopt an integrative systems biology approach to identify key dysregulated molecular pathways involved in Metabolic Syndrome (MetS), MASLD, and MASH. These insights are then validated using advanced translational models, including:

• Dietary and genetically engineered mouse models (GEMMs) of MASH and MASH-HCC;
• State-of-the-art in vitro systems.

Ultimately, our goal is to discover and validate biomarkers and therapeutic targets for early detection, risk stratification, and treatment of MASH and MASH-HCC.

In collaboration with the Roger Williams Institute of Liver Studies & Kings College of London (UK)