Ping Xie
Assistant Professor

Molecular mechanisms of immune regulation and cancer pathogenesis

Our ongoing research focuses on TRAF3, a cytoplasmic adaptor protein utilized by the tumor necrosis factor receptor (TNF-R) superfamily and Toll-like receptors (TLRs) for signaling. Aberrant functions of these receptors contribute to the pathogenesis of a variety of human diseases, including autoimmune diseases, infectious diseases, and cancers. Understanding how TRAF3 regulates signaling by these receptors inside cells is thus critical for designing vaccines and treatment strategies for human diseases. To address this and to circumvent the early lethality limitation of TRAF3 knockout mice, we generated conditional TRAF3-/- (TRAF3flox/flox) mice. Through characterization of B cell-specific and T cell-specific TRAF3-/- mice, we have discovered pivotal and diverse functions of TRAF3 in B and T lymphocytes. In particular, we found that B cell-specific TRAF3-/- mice display severe peripheral B cell hyperplasia, splenomegaly, and autoimmune reactivity. We are currently investigating the contributions of TRAF3 in B lymphomagenesis. We will also examine the functions of TRAF3 in innate immunity and inflammation by generating myeloid cell-specific TRAF3-/- mice. Furthermore, we are developing a new research program to explore whether and how protein arginine methylation and arginine methyltransferases regulate immune responses and cancer pathogenesis. Knowledge gathered from our research programs will contribute to a better understanding of the regulation of immune responses and cancer pathogenesis.

Selected Publications

Xie, P., Kraus, Z.J., Stunz, L.L. and Bishop, G.A. (2008) Roles of TRAF molecules in B lymphocyte function. Cytokine growth factor Rev 19:199-207.

Xie, P., Stunz, L.L., Larison, K.D., Yang, B. and Bishop, G.A. (2007) Tumor necrosis factor receptor-associated factor 3 is a critical regulator of B cell homeostasis in secondary lymphoid organs. Immunity 27:253-67.

Bishop, G.A. and Xie, P. (2007) Multiple roles of TRAF3 signaling in lymphocyte function., Immunol Res 39:22-32.

Bishop, G.A., Moore, Xie, P., Stunz, L.L. and Kraus, Z.J. (2007) TRAF proteins in CD40 signaling. Adv Exp Med Biol 597:131-51.

Xie, P., Hostager, B.S., Munroe, M.E., Moore, C.R. and Bishop, G.A. (2006) Cooperation between TNF receptor-associated factors 1 and 2 in CD40 signaling. J Immunol 176:5388-400.

Wu, S., Xie, P., Welsh, K., Li, C., Ni, C.Z., Zhu, X., Reed, J.C., Satterthwait, A.C., Bishop, G.A. and Ely, K.R. (2005) LMP1 protein from the Epstein-Barr virus is a structural CD40 decoy in B lymphocytes for binding to TRAF3. J Biol Chem 280:33620-6.

Xie, P. and Bishop, G.A. (2004) Roles of TNF receptor-associated factor 3 in signaling to B lymphocytes by carboxyl-terminal activating regions 1 and 2 of the EBV-encoded oncoprotein latent membrane protein 1. J Immunol 173:5546-55.

Xie, P., Hostager, B.S. and Bishop, G.A. (2004) Requirement for TRAF3 in signaling by LMP1 but not CD40 in B lymphocytes. J Exp Med 199:661-71.

Shepard, L.W., Yang, M., Xie, P., Browning, D.D., Voyno-Yasenetskaya, T., Kozasa,T. and Ye, R.D. (2001) Constitutive activation of NF-kappa B and secretion of interleukin-8 induced by the G protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus involve G alpha(13) and RhoA. J Biol Chem 276:45979-87.

Catlett, I.M., Xie, P., Hostager, B.S. and Bishop, G.A. (2001) Signaling through MHC class II molecules blocks CD95-induced apoptosis. J Immunol 166: 6019-24.