The major research interest in Dr. Rui’s laboratory is the mechanisms of the JAK-STAT signaling pathway in lymphomagenesis. The goal of his research is to discover effective molecular targets in this pathway for therapeutic, diagnostic and prognostic development of human lymphoma. Dr. Rui previously studied primary mediastinal and Hodgkin lymphoma, both of which share biological and molecular features. One common genetic alteration in these two cancers is an amplification of the chromosome 9p24 region where JAK2 resides. JAK2 and the co-amplified JMJD2C, a gene encoding histone demethylase, cooperate to promote cancer cell survival. The molecular mechanism of this synergism is histone modifications with H3K9 demethylation by JMJD2C and H3Y41 phosphorylation by JAK2, both of which lead to opening up chromatin structure for transcription of their target genes. Some of JAK2 target genes will be potential molecular targets since their expression is required for cancer cell survival or can evade tumor immunity.
Recently, Dr. Rui has extended this finding and discovered a similar epigenetic mechanism by the JAK1 kinase in aggressive diffuse large B-cell lymphoma. His research team will employ a multidisciplinary approach, using biochemistry, RNA interference, next-generation sequencing (including ChIP-seq and RNA-seq), and systems biology methods, to identify JAK1 target genes in this lymphoma and to investigate crosstalk between JAK1 and other signaling pathways, such as NF-κB.
Dr. Rui’s interests also include investigations of the F-box protein FBXO10. His recent work has characterized FBXO10 as a potential tumor suppressor that targets the anti-apoptotic protein BCL2 for proteasomal degradation. The gene FBXO10 is infrequently mutated in diffuse large-B cell lymphomas but has reduced expression in a vast majority of these patient samples. Dr. Rui and his research team are currently exploring the role of FBXO10 in other types of lymphoma including mantle cell lymphoma. In addition, Dr. Rui will collaborate with Dr. Michael Gould to dissect FBXO10 function in vivo using FBXO10 knockout animal models established in his lab.