RESEARCH NETWORK FOR NEW STRATEGIES IN IMMUNOTHERAPY
T1 T1 - Identification and Characterization of Target Genes in B Cell Tumors
Issues of future research:
The Wnt signal transduction pathway is one of the major forms of cell-cell communication in the development of multicellular organisms. This signaling pathway regulates the generation and proliferation of specific cell types. In particular, Wnt signals regulate the proliferation of pre-B cells. In some forms of B cell tumors, Wnt signaling appears to be deregulated. Wnt signals are transduced into the cell nucleus by the transcription factor LEF1 (lymphoid enhancer factor 1), resulting in the alteration of the expression of target genes. Although the biochemical and molecular mechanisms of Wnt signaling have been elucidated, the identity of biologically relevant target genes remains obscure.This project concerns the identification of genes in pre-B cells that are regulated by Wnt signals and LEF1. cDNA clones will be isolated, which are differentially expressed in pre-B cells from wild type and LEF1 knock-out mice or in normal B cells and chronic lymphocytic leukemic (CLL) cells.
Our cooperation partner, Sireen, will chemically synthesize small molecules that should specifically interfere with the function of the target proteins.The functional characterization of Wnt target genes should allow future therapies of some B cell tumors and other tumors, in which Wnt signaling is deregulated.