Leukemias and lymphomas can occur when there is perturbation in the normal development and activation of B cells. Germinal centers are the critical environment in which antigen-activated B cells further develop and differentiate into antibody-secreting plasma cells or memory B cells. Within germinal centers, B cells diversify the antibody repertoire by somatic hypermutation and class switch recombination of the immunoglobulin genes.
This process subjects B cells to potential loss of genomic integrity through aberrant mutations and chromosomal breakage. Indeed, many lymphomas frequently bear these abnormal genetic alterations, some of which have been implicated as causal factors of lymphomagenesis through disruption of signal transduction pathways that regulate normal cellular proliferation and survival (Science 319: 1676-9 (2008); Nature 463: 88-92 (2010)).
The research in our laboratory aims to discover abnormal signal transduction pathways and elucidate the molecular pathogenesis of germinal center-derived B cell tumors as well as other hematologic malignancies. Our approaches combine genome-scaled functional genetic screens using RNA interference technology in tumor cell line models with validation in human primary tumor biopsies and mouse models. Better understanding the molecular basis of aberrant signal transduction pathways critical for cancer growth will allow us to identify effective molecular targets and devise better therapeutic strategies for cancer treatments.