Postdoctoral positions are available to work on CONNASHION, an ERC Consolidator Grant project at Vita-Salute San Raffaele University in Milan, Italy.

The liver’s blood vessels do more than supply oxygen and nutrients: they help determine what hepatocytes do at different positions within the lobule. Along this vascular axis, hepatocytes express different sets of genes and perform distinct metabolic functions, a pattern known as liver zonation. Endothelial cells help establish and maintain this organisation through local signals known as angiocrine signals. As chronic liver disease progresses, this spatial organisation breaks down. Whether its loss helps drive the transition from reversible injury to fibrosis remains an open question.

Our hypothesis is that changes in endothelial signalling contribute to the loss of zonation and actively drive disease progression. If so, the liver vasculature could offer a way to intervene by restoring the signals that organise hepatocyte function.

To investigate this, we will combine mouse models of metabolic dysfunction-associated steatohepatitis (MASH) with advanced imaging and spatially resolved multi-omics. We will map how the liver vasculature and hepatocyte zonation change across disease stages, and ask which alterations precede fibrosis. These spatial changes could help distinguish stages of disease that are difficult to separate using current diagnostic and prognostic approaches.