I have a background in Pediatrics, Immunology and Human Genetics, which has motivated me to conduct researches on human immunology. Since obtaining an independent research position, I have developed two major projects researching Notch-mediated T cell regulation and genetic studies of familial human immune-mediated diseases. Our group was the first to identify the contribution of Notch in CD4 T cell differentiation. We also identified Notch signaling as an essential intracellular signal for exerting CD8 T cell cytotoxicity, the differentiation of IL-22-producing T cells, the development of intestinal macrophages and the maintenance of memory CD4 T cells. I continue to investigate the roles of Notch in adaptive immune responses while also establishing tools to modify Notch signaling as potential therapies for human autoimmune disease. As for the genetic studies on human inflammatory disorders, our group has tried to identify cases of familial immune-mediated diseases without a known genetic cause in order to identify new genes that cause human immune-mediated diseases. We found that PSMB8 is a causative gene for familial autoinflammatory disorders with lipodystorophy, which provided new insights into the pathogenesis of autoinflammatory syndromes and the physiological role of immunoproteasomes. We also identified DNase1 and NLRC4 as causative genes for systemic lupus erythematosus and familial cold autoinflammatory syndrome, respectively. We have continued to identify causative genes for familial inflammatory or immunodeficiency diseases to understand human immune system.
Koji Yasutomo, MD, PhD