Granzyme K is a so-called orphan granzyme, meaning that it has not been studied in depth. This protease is highly enriched at sites of inflammation ranging from autoimmune diseases to infections and cancers, but its functions are not clear. Using functional assays of human samples as well as mouse models of inflammatory arthritis, we will determine the effects of granzyme K on other cells in synovium and other tissues.

The spatial organization of a tissue plays an enormous role in its function, both in health and disease. We will determine the niches and neighborhoods of GzmK+ CD8 T cells and NK cells in human rheumatoid arthritis synovial tissue to better understand the role GzmK+ lymphocytes play in regulating inflammatory pathways in RA.

CD8 T cells and NK cells expressing a protease called granzyme K (GzmK) are highly enriched in inflamed synovial tissue in rheumatoid arthritis and other autoimmune diseases. We are investigating the pathways that lead T cells and NK cells to adopt a GzmK+ phenotype.