Animal and plant cells typically exist in physiologically controlled environments that are always nutrient-rich, yet they proliferate selectively. This is because specific signals from other cells stimulate or limit their growth and proliferation according to rules that benefit the organism as a whole. The goal of our research is to understand some of the genetic logic or regulatory “circuitry” - that controls cell growth and coordinates it with cell cycle progression in vivo, in the Drosophila model system. Our approach is to use genetic screens to identify genes that act as dedicated regulators of cell growth or the cell cycle, and then determine how these are controlled, upstream, by genetic programming and cell signaling and how, downstream, they regulate growth-related metabolism and the cell cycle control apparatus. In the lab we apply classical and molecular genetics, mosaic analysis, cell imaging, flow cytometry, and gene expression profiling in a number of different cell and tissue types. We aim to define new genes and regulatory pathways involved in growth control that will impact general paradigms in cell and developmental biology, and which may also have relevance to topics in human health such as cancer biology, stem cell therapy, and metabolic disease. Current topics of interest include: Cell cycle exit at differentiation, Endocycle control, TOR signaling, and Intestinal stem cell regulation.
Zielke, N., Kim, K. J., Tran, V., Shibutani, S. T., Bravo, M-J., Nagarajan, van Straaten, M. S., Woods, B., von Dassow, G., Rottig, C., Lehner, C. F., Grewal, S., Duronio, R. J., and Edgar, B. A. (2011) Control of Drosophila endocycles by E2F and CRL4Cdt2 Nature 480(7375):123-7
Jiang, H., Grenley, M., Bravo, M.J., Blumhagen, R.Z., Edgar, B.A. (2010) EGFR/Ras/MAPK signaling mediates adult midgut epithelial homeostasis and regeneration in Drosophila. Cell Stem Cell 8:1-12.
Wang, T., Lao, U., Edgar, B. A. (2009) TOR-mediated autophagy regulates cell death in Drosophila neurodegenerative disease. J. Cell Biol. 186:703-711.
Jiang, H., Patel, P. H., Kohlmaier, A., Grenley, M. O., McEwen, D., and Edgar, B. A. (2009) Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell 137:1343-1355
Shibutani, S.T., de la Cruz, A.F., Tran, V., Turbyfill, W.J., Reis, T., Edgar, B.A., and Duronio, R.J. (2008) Intrinsic negative cell cycle regulation provided by PIP box- and Cul4Cdt2-mediated destruction of E2f1 during S phase. Developmental Cell 15:890-900.
Buttitta, L., Katzaroff, A., Perez, C., de la Cruz, A., Edgar, B.A. (2007) A double-assurance mechanism controls cell cycle exit upon terminal differentiation in Drosophila. Dev. Cell 12:631-643.
Grewal, S.S., Li, L., Orian, A., Eisenman, R.N., Edgar, B.A. (2005) Myc-dependent regulation of ribosomal RNA synthesis during Drosophila development. Nat Cell Biol 7: 295-302.
Saucedo, L. J., Gao, X., Chiarelli, D. A., Li, L., Pan, D., and Edgar, B. A. (2003) Rheb promotes cell growth as a component of the insulin/TOR signalling network. Nat Cell Biol 5: 566-571.
Britton, J.S., Lockwood, W.B., Cohen, S.M., and Edgar, B.A. (2002) Drosophila’s Insulin/PI3-Kinase Pathway Coordinates Cellular Metabolism with Nutritional Conditions. Dev. Cell 2, 239249.
Buttitta, L.A., Edgar, B.A. (2007) Mechanisms controlling cell cycle exit upon terminal differentiation. Current Opinion in Cell Biology, 19 (6), 697-704. (Review).
Jiang H, Edgar BA. (2011) Intestinal stem cells in the adult Drosophila midgut. Experimental Cell Research 317(19):2780-2788,