Katja Brückner, PhD


The Brückner lab studies mechanisms of development, hematopoiesis and cancer, using the fruitfly Drosophila melanogaster as a model organism.

Regulation of hematopoiesis. The Peripheral Nervous System (PNS) has been identified as a functional component of hematopoietic microenvironments and other stem cell niches. However, it remains largely unknown how sensory neurons and their inputs direct blood cell development and homeostasis. To address these questions at the cellular and molecular level, we study hematopoiesis in the optically transparent Drosophila larva. In this system, blood cells (hemocytes) colonize hematopoietic pockets and develop in direct physical contact with segmentally repeated sensory PNS clusters. Hemocytes functionally rely on the PNS for their attraction and trophic survival, and are induced to proliferate in these microenvironments. Our lab investigates the cellular and molecular mechanisms by which constitutive and neuronal activity-dependent PNS ‘circuits’ regulate hematopoiesis and blood cell homeostasis.

Cell lifespan control. Receptor tyrosine kinases of the PDGF/VEGF family play essential roles in the survival and proliferation of blood cells and other cell types; over-activation of these receptors is key in the pathology of many cancers. We have shown that the Drosophila PDGF/VEGF receptor (PVR) controls embryonic blood cell survival in vivo and in cell culture, thereby providing a valuable model for cell lifespan control. Using a genome-wide cell-based RNAi screen we identified modifiers of PVR signaling that change cell lifespan. The screen revealed tumor suppressors and oncogenes, and novel genes expected to have comparable functions. Our lab dissects the signaling pathways downstream of these genes, to determine common motifs and differences in the signaling networks that regulate cell lifespan.

Epithelial plasticity. Epithelial plasticity and epithelial-to-mesenchymal transition (EMT) play important roles during normal development and in the pathology of tumor metastasis and fibrosis. In many of these cases, Transforming Growth Factor-β (TGF-β) or Bone Morphogenetic Protein (BMP) cooperate with Akt signaling. However, the molecular basis of this cooperation remains incompletely understood. We address this question using KaBrü1D, a Drosophila epithelial cell line that undergoes BMP/decapentaplegic (dpp) induced epithelial plasticity. Based on an RNAi screen, expression profiling and ChIP analyses we identified genes that are essential for epithelial plasiticity, including all positive regulators of the Akt/Tor pathway. Our lab determines the mechanism of cooperation between BMP and Akt signaling, for which we particularly focus on the differential binding of transcriptional targets.