Research projects in our laboratory are aimed at studying the biology of cell populations capable of inducing or suppressing graft vs host disease as well as cells capable of promoting a graft vs tumor effect. In particular we are studying:

1) The clinical utility of expanded cytotoxic cells for immunotherapy. We have developed animal models utilizing mice with severe combined immunodeficiency (SCID) which will accept human tumor cells or murine model systems of syngeneic and allogeneic transplantation. In some instances the tumor cells are transfected with the bioluminescent marker luciferase so that the tumor cell growth can be quantitatively tracked in living animals. Using these model system we are studying the clinical efficacy of the expanded cytotoxic cells.

2) The interaction between the cytotoxic effector cells and a variety of tumor cell targets is under study. The role of granzyme/perforin and fas mediated pathways as well as the cell surface molecule NKG2D in cytotoxicity is under study.

3) We are exploring the biological impact of phenotypically defined populations of regulatory T cells on graft vs host disease and graft vs tumor reactions.

4) We are utilizing bioluminescent techniques to study these complex biological processes by either labelling the tumor or effector cell populations with the light emitting luciferase gene such that small numbers of cells can be tracked non-invasively, sensively and quantitatively.

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• Nguyen VH, Shashidhar S, Chang DS, Ho L, Kambham N, Bachmann M, Brown JM, Negrin RS "The impact of regulatory T cells on T cell immunity following hematopoeitic cell transplantation." Blood 2007; More
• Beilhack A, Schulz S, Baker J, Beilhack GF, Nishimura R, Baker EM, Landan G, Herman EI, Butcher EC, Contag CH, Negrin RS "Prevention of acute graft-versus-host disease by blocking T-cell entry to secondary lymphoid organs." Blood 2007; More
• Zeiser R, Leveson-Gower DB, Zambricki EA, Kambham N, Beilhack A, Loh J, Hou JZ, Negrin RS "Differential impact of mTOR inhibition on CD4+CD25+Foxp3+ regulatory T cells as compared to conventional CD4+ T cells." Blood 2007; More
• Zeiser R, Youssef S, Baker J, Kambham N, Steinman L, Negrin RS "Preemptive HMG-CoA reductase inhibition provides graft-versus-host disease protection by Th-2 polarization while sparing graft-versus-leukemia activity." Blood 2007; 110: 13: 4588-98 More
• Zeiser R, Zambricki EA, Leveson-Gower D, Kambham N, Beilhack A, Negrin RS "Host-derived interleukin-18 differentially impacts regulatory and conventional T cell expansion during acute graft-versus-host disease." Biol Blood Marrow Transplant 2007; 13: 12: 1427-38 More