Macrophages are essential regulators of tissue homeostasis and regeneration. Recent advances in single cell and spatial technologies have expanded our understanding of macrophage heterogeneity and led to the identification of Lipid Associated Macrophages (LAMs). As this subset of macrophages, defined by their expression of Trem2, Gpnmb and Spp1, has been described across tissues and injury contexts, they represent an interesting potential target for therapeutic intervention. Indeed in the liver, the host laboratory has identified LAMs across different injury contexts including fibrosis and steatotic liver disease. While data to date suggest LAMs may play a protective role in the liver, their exact functions remain unclear. Moreover, the factors governing LAM development as well as LAM-fates post injury remain to be studied. As this information is critical for these cells to be leveraged therapeutically, in LiverLAMs, I aim to investigate LAM development, functions and fates in the fibrotic liver. To achieve this, I will utilize novel mouse models generated by the host lab which specifically target LAMs alongside single cell and spatial technologies and an in vivo CRISPR screen to investigate LAMs over time in liver fibrosis and repair. Finally, I will utilize this knowledge to generate iPSC-derived LAMs as a proof of concept, which could later be utilized therapeutically offering hope for patients with fibrosis and other inflammatory diseases where LAMs may be beneficial.