Angus Thomson, PhD
Office: W1544 BST
Lab: E1500 BST
Pittsburgh, PA 15213
- Distinguished Professor of Surgery
Inhibition of the mammalian target of rapamycin has marked effects on both DC and regulatory T cell functions. Both the molecular basis of these effects and their therapeutic applications are being investigated in vitro and in vivo. Funded by NIH Grant R01 AI67541
Here we seek to elucidate the role of dendritic leukocytes, - highly specialized antigen-presenting cells, in determining the balance between organ transplantation tolerance and immunity. Studies involve elucidation of the roles of key signaling molecules in the dialogue between dendritic cells (DC) and T cells, and investigation of the function of DC in organ allograft models. Funded by ROTRF Grant 874279717
This study is designed to evaluate the tolerogenicity of donor- or recipient-derived dendritic cell subsets for the promotion of transplantation tolerance in the clinic. Both biologic and pharmacologic agents known to promote DC tolerogenicity will be evaluated for their capacity to maximize the ability of the donor DC to induce alloantigen-specific T cell unresponsiveness. Funded by NIH Grant U01 AI/DK 51698.
We are evaluating the ability of ex-vivo propagated regulatory T cells to promote transplant tolerance in pre-clinical heart transplant models. Funded by NIH Grant U01 91197
- Rosborough, B. R., D. Raich-Regue, B. M. Matta, K. Lee, B. Gan, R. A. Depinho, H. Hackstein, M. Boothby, H. R. Turnquist, and A. W. Thomson. 2013. Murine dendritic cell rapamycin-resistant and rictor-independent mTOR controls IL-10, B7-H1 and regulatory T cell induction. Blood Epub ahead of print.
- Matta, B. M., G. Raimondi, B. R. Rosborough, T. L. Sumpter, and A. W. Thomson. 2012. IL-27 production and STAT3-dependent upregulation of B7-H1 mediate immune regulatory functions of liver plasmacytoid dendritic cells. J. Immunol. 188:5227-5237.
- Thomson, A. W., H. R. Turnquist, and G. Raimondi. 2009. Immunoregulatory functions of mTOR inhibition. Nat Rev Immunol 9:324-337.
- Turnquist, H. R., T. L. Sumpter, A. Tsung, A. F. Zahorchak, A. Nakao, G. J. Nau, F. Y. Liew, D. A. Geller, and A. W. Thomson. 2008. IL-1beta-driven ST2L expression promotes maturation resistance in rapamycin-conditioned dendritic cells. J. Immunol. 181:62-72.
- Sumpter, T. L., V. Packiam, H. R. Turnquist, A. Castellaneta, O. Yoshida, and A. W. Thomson. 2011. DAP12 promotes IRAK-M expression and IL-10 production by liver myeloid dendritic cells and restrains their T cell allostimulatory ability. J. Immunol. 186:1970-1980.
- Raimondi, G., T. L. Sumpter, B. M. Matta, M. Pillai, N. Corbitt, Y. Vodovotz, Z. Wang, and A. W. Thomson. 2010. Mammalian target of rapamycin inhibition and alloantigen-specific regulatory T cells synergize to promote long-term graft survival in immunocompetent recipients. J. Immunol. 184:624-636.
- Turnquist, H. R., J. Cardinal, C. Macedo, B. R. Rosborough, T. L. Sumpter, D. A. Geller, D. Metes, and A. W. Thomson. 2010. mTOR and GSK-3 shape the CD4+ T cell stimulatory and differentiation capacity of myeloid DC following exposure to LPS. Blood 115:4758-4769.
- Morelli, A. E., and A. W. Thomson. 2007. Tolerogenic dendritic cells and the quest for transplant tolerance. Nat Rev Immunol 7:610-621.
- Dendritic cells, rapamycin and transplant tolerance
- Understanding the role of dendritic cells in liver transplant tolerance
- Transitioning regulatory DC from the laboratory to the clinic