Katja Brückner, Ph.D.
	Drosophila models for cell differentiation and cancer
	Email: katja.brueckner@ucsf.edu
Selected Publications | Complete Publications

Our lab takes advantage of the conservation of invertebrate and vertebrate biology, using the fruitfly Drosophila melanogaster as a model organism. Our goal is the identification of novel genes that (a) are involved in the maintenance and differentiation of stem and progenitor cells during normal development, and (b) are deregulated in cancer cells. Human counterparts of these genes may in the future serve as molecular targets for medical applications.

(1) Cell survival and development in the hematopoietic system PDGF/VEGF receptors play essential roles in the proliferation and survival of hematopoietic stem and progenitor cells. Activation of these receptors is a key step in the transformation of leukemic and other tumor cells. We have shown that the Drosophila PDGF/VEGF receptor (PVR) has comparable functions in the control of embryonic blood cell survival in vivo and in cell culture. Using a cell-based assay we screened the entire Drosophila genome for genes that modify PDGF/VEGF Receptor signaling. Among the identified genes we anticipate novel tumor suppressors and oncogenes, as our screen revealed many known members of these groups. We aim to verify the role of these genes across species, using Drosophila genetics and cell culture, as well as mouse and human hematopoietic and embryonic stem cell lines, and mouse leukemia models.

In a more recent project, we address whether Drosophila may be an appropriate model to study self-renewal in the hematopoietic system, which would allow genetic approaches to identify the factors that govern stem cell maintenance and differentiation.

(2) Differentiation potential of pluripotent precursors and epithelial plasticity The Drosophila embryo carries precursors of all adult tissues, the so-called imaginal cells. Under certain conditions, these cells retain pluripotent progenitor capacity. To study their differentiation potential, we established a number of novel, presumably imaginal Drosophila cell lines (KaBrü1-8), which show a wide range of morphological, cellular and molecular features. KaBrü1D cells have epithelial characteristics and serve as a system to study the effects of the TGF-? family ligand Decapentaplegic (Dpp), inducing changes that resemble epithelial-to-mesenchymal transition as known in mammalian development and tumor metastasis. Besides studying KaBrü cells in culture, we explore their homing and differentiation capacity in the live animal. Combining the advantages of external accessibility of cell lines and genetic manipulation of Drosophila in vivo, we will elucidate the factors that govern the differentiation of imaginal cells and translate this knowledge toward mammalian pluripotent progenitors.

Selected Publications

Brückner K, Pasquale EB, Klein R. (1997) Tyrosine phosphorylation of transmembrane ligands for Eph receptors. Science, 275(5306):1640-3.

Brückner K, Labrador JP, Scheiffele P, Herb A, Seeburg PH, Klein R. (1999) EphrinB ligands recruit GRIP family PDZ adaptor proteins into raft membrane microdomains. Neuron, 22:511-524.

Brückner K, Perez L, Clausen H, Cohen S. (2000) Glycosyltransferase activity of Fringe modulates Notch-Delta interactions. Nature, 406(6794):411-5.

Brückner K., Kockel, L., Duchek, P., Luque, C. M., Rørth, P., and Perrimon, N. (2004). The PDGF/VEGF Receptor controls blood cell survival in Drosophila. Dev Cell 7(1):73-84.

Information last updated April 2007