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Our primary research interests are in regulation of the immune system by CD1d-reactive NKT cells and how to utilize this knowledge clinically in cancer and other diseases. CD1d is expressed on myeloid cells, lymphocytes, heart, liver, and in the gut. Bi-directional interactions between CD1d+ cells and CD1d-reactive NKT profoundly influence immune responses. Our recent contributions include establishing a physiological role for CD1d-reactive NKT and defining the human populations of these cells in health and disease. Advanced cancer patients have few and anti-inflammatory polarized CD1d-reactive NKT, which may suppress their anti-tumor activity. Bone marrow CD1d-reactive T cells have a profound anti-inflammatory bias with potential to suppress graft-versus-host disease. Conversely, HCV+ human liver also contains large numbers of CD1d-reactive NKT, but with a pro-inflammatory bias, which may contribute to both protective and pathogenic responses in hepatitis and hepatocellular carcinoma. These results support a role for these cells in immune decision making with potential therapeutic applications. We are supporting clinical trials to exploit NKT cells in cancer and other diseases. We are also following up identification of a physiological role for CD1d-reactive NKT in resistance to viral infections through activation of NK and conventional T cells. Finally, we have identified a protective role of NKT cells in obesity and consequent metabolic syndrome.