Discovered that UV-irradiation causes systemic immunosuppression, contributing to carcinogenesis, and described the cellular and molecular mechanisms underlying UV-induced immunosuppression.
Ullrich SE. Mechanisms underlying UV-induced immune suppression [review]. Mutat Res. 2005;571(1-2):185-205.
Discovered the origin in the thymus gland of regulatory lymphocytes that police and protect the body by inhibiting T-cells that can cause autoimmune disease.
Watanabe N, Wang YH, Lee HK, Ito T, Wang YH, Cao W, Liu Y-J. Hassall’s corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature. 2005;436(7054):1181-1185.
Characterized two functional receptors uniquely expressed by human plasmacytoid dendritic cells (pDCs) and discovered a major intracellular signaling pathway, through which pDC receptors modulate immune responses.
Cao W, Rosen DB, Ito T, Bover L, Bao M, Watanabe G, Zhang L, Lanier LL, Liu Y-J. Plasmacytoid Dendritic Cell-Specific Receptor ILT7-Fc epsilon RI gamma Inhibits Toll-Like Receptor-Induced Interferon Production. J. Exp. Med. 203:1399-1405, 2006.
Cao W, Zhang L, Rosen DB, Bover L, Watanabe G, Bao M, Lanier LL, Liu Y-J. BDCA2/FceRIg Complex Signals through a Novel BCR-like Pathway in Human Plasmacytoid Dendritic Cells. PLoS Biology, in press, 2007.
Created a chimeric antigen receptor that can fully activate T-cells upon binding of antigen, leading to tumor-cell lysis, T-cell proliferation and cytokine production.
Kowolik CM, Topp MS, Gonzalez S, Pfeiffer T, Olivares S, Gonzalez N, Smith DD, Forman SJ, Jensen MC, Cooper LJ. CD28 costimulation provided through a CD19-specific chimeric antigen receptor enhances in vivo persistence and antitumor efficacy of adoptively transferred T cells. Cancer Res. 2006;66(22):10995-11004.
Gene therapy can improve the ability of T cells, a type of immune cell, to target human cancers. To safely insert desired genes into T cells, adapted a gene transfer system found in fish called Sleeping Beauty. Demonstrated that Sleeping Beauty can be used to efficiently introduce genes that will redirect the specificity of T cells for tumor cells. Achieved FDA approval to test Sleeping Beauty in clinical trials using T cells rendered specific for one type of lymphoma.
Singh H, Manuri PR, Olivares S, Dara N, Dawson MJ, Huls H, Hackett PB, Kohn DB, Shpall EJ, Champlin RE, Cooper LJ. Redirecting specificity of T-cell populations for CD19 using the sleeping beauty system. Cancer Res. 2008;68:2961-2971.