Sex differences in adipose–liver communication

Adipose tissue and the liver exchange metabolic and inflammatory signals. We investigate how this communication differs between women and men with metabolic dysfunction-associated steatotic liver disease (MASLD), and which adipocyte and macrophage states are associated with hepatocyte stress and injury.

Using paired human visceral adipose and liver tissues, we study adipocyte, macrophage, and hepatocyte states and the relationships between them. These tissues reveal sex-associated cell states and relationships across the adipose–liver axis.

The human tissue patterns guide experiments to determine how changes in adipose-derived signals affect hepatocyte stress and injury. This work connects human tissue analysis to functional perturbation while keeping changes in the adipose signal environment and hepatic sensitivity as distinct biological questions.

Macrophage states in human atherosclerosis

We investigate how macrophage states shape chronic inflammation and clinical risk in human atherosclerosis. We helped build one of the first single-cell atlases of full human atherosclerotic plaques, revealing distinct immune and stromal states within diseased tissue.

We subsequently linked plaque macrophage burden and inflammatory lipid-associated macrophage markers to cardiovascular events after carotid endarterectomy. This work connects cell states measured in human tissue to later clinical outcomes. The same state-resolved approach now informs our studies of macrophages in visceral adipose and liver tissue.

Transcriptional and epigenetic control of inflammation

Human tissue atlases show where disease-associated cell states occur. Functional experiments are needed to identify the regulators that create and maintain those states. We use CRISPR and CROP-seq screens with transcriptomic profiling to test how histone-modifying enzymes control macrophage responses to inflammatory stimuli.

This work identified KDM5C, KAT2B, PRMT6, and CARM1 as regulators of macrophage activation. Follow-up experiments examine how these chromatin regulators balance baseline inflammatory tone with responses to stimulation.

By combining perturbation experiments with cell states observed in human tissues, we test which transcriptional and epigenetic mechanisms contribute to inflammation in atherosclerosis and MASLD.