Deciphering the splicing blueprint of human myeloid cells in non-alcoholic steatohepatitis

Non-Alcoholic Steatohepatitis (NASH) is on the verge of becoming the leading cause of liver-related morbidity and mortality in the foreseeable future.

The FDA´s approval of the inaugural medication for NASH treatment in March 2024 brought a glimmer of hope to those afflicted by this condition.

Yet, the limited treatment options highlight an urgent need for a deeper grasp of the intricate mechanisms underlying NASH to identify alterative treatment strategies.

This project is dedicated to exploring the role of alternative splicing in NASH, specifically concentrating on human liver myeloid cells, and circulating monocytes.

Our objective is to unravel how alternative splicing shapes the diverse phenotypes of human myeloid cells during NASH progression.

To achieve this, we will develop innovative computational tools to characterize alternative splicing and single nucleotide variants at both single cell and subpopulation levels.

Further, we will investigate the impact of SNVs and the tissue microenvironment on RNA splicing in cells disrupted by NASH.

By integrating spatial and single-cell omics data, our research will illuminate the intricate inter- and intracellular regulatory networks of alternative splicing dynamics during NASH progression.

Crucial findings will be validated experimentally using established pre-clinical models, aiming to discover novel splicing-centric biomarkers and therapeutic targets for NASH patients.