Division of Cell Growth and Proliferation
Prof. Dr. Bruce Edgar
The precise control of cell proliferation is essential for development in growing animals and plants, and for tissue homeostasis in adults. Loss of this control is a pre-requisite for carcinogenesis. Research in Dr. Edgar's group focusses on the mechanisms that control cell cycle progression and cell growth in the Drosophila model system. We use diverse molecular, genetic, and cytological approaches to discover, and then characterize, genes and pathways that regulate the growth and proliferation of cells in vivo, in several different organs and tissue types in the fly. Many such genes can be shown to oncogenes or tumor suppressors in humans, and thus the yield of these basic studies fuels more applied cancer research. Ongoing projects address the control of cell cycle exit at differentiation by the E2F, Retinoblastoma, and APC complexes, the mechanism of growth-dependent endoreplication cell cycles, nutrient-dependent cell growth via the insulin-TOR signaling network, and the regulation of homeostatic and neoplastic growth in the fly gut by intestinal stem cells.
The laboratory continues to focus on the regulation of the cell growth and proliferation in several cell types in Drosophila. The main projects concern:
Cell Cycle Exit at Differentiation
- Regulation of E2F/Rb, CycE, and Cdc25 at cell cycle exit in the fly wing and eye
- Cell cycle control by Drosophila Hsp83 and APC
- Screening for regulators of cell cycle exit in Drosophila
- Control of Drosophila Endocycles by E2F and APC
- Growth regulation of the Endocycle
- Mechanism of endocycling in murine trophoblast giant cells
- Intestinal stem cell control by cell signaling pathways including Jak/Stat, EGFR/Ras/MApK, Hippo, and others
- Whole genome genetic screens for regulators of intestinal stem cell proliferation and differentiation
- Cell cycle controls in intestinal stem cells and their progeny
- Development of in vitro intestinal stem cell culture
Prof. Edgar's Homepage at ZMBH
Jiang H, Patel PH, Kohlmaier A, Grenley MO, McEwen DG, and Edgar BA: Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell 137, 1343-55, 2009.
Jiang H, Grenley MO, Bravo MJ, Blumhagen RZ, Edgar BA: EGFR/Ras/MAPK signaling mediates adult midgut epithelial homeostasis and regeneration in Drosophila. Cell Stem Cell 8: 84-95, 2011.
Shibutani ST, de la Cruz AF, Tran V, Turbyfill WJ, Reis T, Edgar BA, and Duronio RJ.: Intrinsic negative cell cycle regulation provided by PIP box- and Cul4Cdt2-mediated destruction of E2f1 during S phase. Dev Cell 15: 890-900, 2008.
Shaw RL, Kohlmaier A, Polesello C, Veelken C, Edgar BA, Tapon N: The Hippo pathway regulates intestinal stem cell proliferation during Drosophila adult midgut regeneration. Development 137: 4147-58, 2010.