Research

Transcriptional regulation / STATs

We study mechanisms of transcriptional activation and repression, by focusing on the orchestrating role of Signal Transducers and Activators of Transcription (STATs) on gene transcription and complex pathways activated upon cytokines signaling in normal cells and in malignancy. STATs are latent cytoplasmic transcription factors that transduce signals from activated cell surface receptors to the nucleus to modulate transcription. The mammalian family includes seven STAT members (1, 2, 3, 4, 5a, 5b and 6). STAT5a and

STAT5b are of particular interest as they are activated by a variety of cytokines, constituting important components of various signal transduction pathways. Constitutive activation of STAT5 is a hallmark for hematopoietic malignancies and other types of cancer (e.g. breast and prostate) and understanding of its role is of critical importance today.

To provide insights on STAT5 activation pathways and elucidate mechanisms of STAT5 dependent transcriptional activation or repression, we identify protein complexes and target genes in a genome-wide manner. Patterns of transcription factor binding and interactions can complement and enhance current knowledge on normal cell and tumor behavior based on protein and mRNA analyses. We apply genomic (ChIP-seq, RNA-seq), proteomic approaches (iTRAQ), specific quantitative biotinylation of tagged STAT5, we develop bioinformatics tools to facilitate protein complexes - target genes analysis and we use sensitive inducible systems in mice for investigation of transcription factors role in a tightly controlled temporal and spacial manner.

Additionally, we use Thalassemia as a model to study mechanisms of erythropoiesis and the role of STATs and other transcription factors in this process.