Introduction - Cell Signaling Laboratory | Department of Biochemistry and Molecular Biology

Our goal is to identify the mechanisms by which macrophages take up dead cells, prevent inflammation, and promote tissue regeneration during efferocytosis. Our research group was founded in 1993. At that time, we were primarily interested in the role of transglutaminase 2 (TG2) in the cell death program, because the enzyme is often expressed where cells have died. We identified several functions, but ultimately, it turned out that cells die well without TG2. However, the clearance of dead cells was disrupted due to the lack of TG2 in scavenging macrophages, which led to the development of autoimmune disease in mice. Investigating the role of TG2 led us to understand the process of dead cell clearance and its central role in maintaining tissue turnover, suppressing inflammation, preventing the development of autoimmune diseases, and regulating tissue regeneration. We have also shown that it regulates thymocyte differentiation and is required for skeletal muscle development. Subsequently, we have demonstrated that several other proteins are required for efficient phagocytosis in macrophages and that their absence disrupts the regulation of inflammation, tissue regeneration, and adipose tissue homeostasis. Our work has identified several drug targets that can be used to influence these processes. We are currently investigating the role of inflammation in the development of obesity and the mechanism of muscle cell fusion.