Molecular mechanisms of immune regulation and cancer pathogenesis
Cell Biology and Biochemistry
Research in Dr. Xie’s laboratory focuses on understanding molecular mechanisms of immune regulation and cancer pathogenesis. Regulation of immune cell homeostasis and functionality is central to the proper functioning of the immune system. To understand the molecular mechanisms of immune regulation, we start from a critical regulator of the immune system, a cytoplasmic adaptor protein termed TRAF3. TRAF3 is a signal transducer of a variety of immune receptors, including the tumor necrosis factor-receptor (TNF-R) superfamily, Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs), among others. By generating and characterizing conditional TRAF3 knockout mice, we found that TRAF3 plays pivotal but distinct roles in different subsets of immune cells, including B cells, T cells, and myeloid cells. Using complementary human and mouse model systems, we are currently investigating the deep mechanisms of B lymphomagenesis induced by TRAF3 inactivation in B cells as well as chronic inflammation and tumor development induced by TRAF3 ablation in myeloid cells. To approach these, we employ a number of cutting-edge strategies in our study, including microarray analyses, proteomics and bioinformatics, metabolome screen by mass spectrometry, transcriptome sequencing (RNA-seq), and chromatin immunoprecipitation coupled with deep sequencing (ChIP-seq). Knowledge gathered from our research programs will have fundamental impacts on our understanding of immune regulation and cancer pathogenesis. This information will provide the necessary platform to design novel therapeutics and treatment strategies to combat human diseases, including cancers, infectious diseases, and chronic inflammatory diseases.