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Bruce Edgar

Professor of Oncological Sciences and Adjunct Professor of Human Genetics

Cell Growth, Cell Cycle, Regeneration, Drosophila, Stem Cells, Organoids

Bruce Edgar

 

Molecular Biology Program

Education

B.A. Swarthmore College

Ph.D. University of Washington

 

Research

Research in the Edgar Lab focuses on the mechanisms that regulate cell growth and proliferation in Drosophila, in human cells, and in the gut epithelium of mice. We use genetics to characterize the programs of cell growth and proliferation that occur during development, tissue maintenance, regeneration, and tumorigenesis, with the goal of finding the genes that act as limiting regulators in each context. We seek to understand how networks of genes and communities of cells in a tissue function as integrated systems that regulate tissue growth according to the needs of the organism. Techniques in use in the lab range from classical and molecular genetics, to high resolution and live imaging, to whole genome gene expression, chromatin, and metabolome profiling.

Current projects in the lab fall in two areas. One set of projects focuses on the mechanisms of stem cell control and epithelial self-renewal in the intestines of Drosophila and mice. A second set of projects addresses how proliferation is controlled by metabolism and growth factor signaling in Drosophila, mice, and human cells. For all of our projects, the over-arching goal is to define new mechanisms involved in cell and tissue growth control that are relevant to basic paradigms in cell and developmental biology, and to issues of human health such as cancer, chronic inflammation, and regenerative medicine.

References (Selected Publications)

  1. Zhang C, Jin Y, Marchetti M, Lewis MR, Hammouda OT, Edgar BA. EGFR signaling activates intestinal stem cells by promoting mitochondrial biogenesis and β-oxidation. Biol. 2022;12:3704-3719.e7. doi: 10.1016/j.cub.2022.07.003. PMID: 35896119.
  2. Øvrebø JI, Bradley-Gill MR, Zielke N, Kim M, Marchetti M, Bohlen J, Lewis M, van Straaten M, Moon NS, Edgar BA. Translational control of E2F1 regulates the Drosophila cell cycle. Proc Natl Acad Sci USA. 2022. doi: 10.1073/pnas.2113704119. PMID: 35074910.
  3. Tamamouna V*, Rahman MM*, Petersson M, Charalambous I, Kux K, Mainor H, Bolender V, Isbilir B, Edgar BA**, Pitsouli C**. Remodeling of oxygen-transporting tracheoles drives intestinal regeneration and tumorigenesis in Drosophila. Nat Cell Biol. 2021;23:497-510. doi: 10.1038/s41556-021-00674-1. Epub 2021 May 10. PMID: 33972730; PMCID: PMC8567841. (*co-first authors; **corresponding authors)
  4. Ahmed SMH, Maldera JA, Krunic D, Paiva-Silva GO, Pénalva C, Teleman AA, Edgar BA. Fitness trade-offs incurred by ovary-to-gut steroid signalling in Drosophila. Nature. 2020;584:415-9. doi: 10.1038/s41586-020-2462-y. PMID: 32641829; PMCID: PMC7442704.
  5. Patel PH, Pénalva C, Kardorff M, Roca M, Pavlović B, Thiel A, Teleman AA, Edgar BA. Damage sensing by a Nox-Ask1-MKK3-p38 signaling pathway mediates regeneration in the adult Drosophila midgut. Nat Commun. 2019;25;10:4365. doi: 10.1038/s41467-019-12336-w. PMID: 31554796; PMCID: PMC6761285.
  6. Xiang J, Bandura J, Zhang P, Jin Y, Reuter H, Edgar BA. EGFR-dependent TOR-independent endocycles support Drosophila gut epithelial regeneration. Nat Commun. 2017;9;8:15125. doi: 10.1038/ncomms15125. PMID: 28485389; PMCID: PMC5436070.
  7. Jin Y, Patel PH, Kohlmaier A, Pavlovic B, Zhang C, Edgar BA. Intestinal stem cell pool regulation in Drosophila. Stem Cell Reports. 2017;6;8:1479-87. doi: 10.1016/j.stemcr.2017.04.002. PMID: 28479306; PMCID: PMC5469868.
  8. Jin Y, Ha N, Forés M, Xiang J, Gläßer C, Maldera J, Jiménez G, Edgar BA. EGFR/Ras signaling controls Drosophila intestinal stem cell proliferation via Capicua-Regulated genes. PLoS Genet. 2015;18;11:e1005634. doi: 10.1371/journal.pgen.1005634. PMID: 26683696; PMCID: PMC4684324.
  9. Patel PH, Dutta D, Edgar BA. Niche appropriation by Drosophila intestinal stem cell tumours. Nat Cell Biol. 2015;17:1182-92. doi: 10.1038/ncb3214. PMID: 26237646; PMCID: PMC4709566.
  10. Korzelius J, Naumann SK, Loza-Coll MA, Chan JS, Dutta D, Oberheim J, Gläßer C, Southall TD, Brand AH, Jones DL, Edgar BA. Escargot maintains stemness and suppresses differentiation in Drosophila intestinal stem cells. EMBO J. 2014;17;33:2967-82. doi: 10.15252/embj.201489072. PMID: 25298397; PMCID: PMC4282643.
  11. Zielke N, Korzelius J, van Straaten M, Bender K, Schuhknecht GFP, Dutta D, Xiang J, Edgar BA. Fly-FUCCI: A versatile tool for studying cell proliferation in complex tissues. Cell Rep. 2014;24;7:588-98. doi: 10.1016/j.celrep.2014.03.020. PMID: 24726363.
  12. Wang T, Blumhagen R, Lao U, Kuo Y, Edgar BA. LST8 regulates cell growth via target-of-rapamycin complex 2 (TORC2). Mol Cell Biol. 2012;32:2203-13. doi: 10.1128/MCB.06474-11. PMID: 22493059; PMCID: PMC3372270.
  13. Zielke N, Kim KJ, Tran V, Shibutani ST, Bravo MJ, Nagarajan S, van Straaten M, Woods B, von Dassow G, Rottig C, Lehner CF, Grewal SS, Duronio RJ, Edgar BA. Control of Drosophila endocycles by E2F and CRL4(CDT2). Nature. 2011;30;480:123-7. doi: 10.1038/nature10579. PMID: 22037307; PMCID: PMC3330263.
  14. 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. 2011;7;8:84-95. doi: 10.1016/j.stem.2010.11.026. PMID: 21167805; PMCID: PMC3021119.
  15. 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. 2010;137:4147-58. doi: 10.1242/dev.052506. PMID: 21068063; PMCID: PMC2990206.
  16. Jiang H, Patel PH, Kohlmaier A, Grenley MO, McEwen DG, Edgar BA. Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell. 2009;26;137:1343-55. doi: 10.1016/j.cell.2009.05.014. PMID: 19563763; PMCID: PMC2753793.
  17. Grewal SS, Evans JR, Edgar BA. Drosophila TIF-IA is required for ribosome synthesis and cell growth and is regulated by the TOR pathway. J Cell Biol. 2007;17;179:1105-13. doi: 10.1083/jcb.200709044. PMID: 18086911; PMCID: PMC2140016.
  18. Buttitta LA, Katzaroff AJ, Perez CL, de la Cruz A, Edgar BA. A double-assurance mechanism controls cell cycle exit upon terminal differentiation in Drosophila. Dev Cell. 2007;12:631-43. doi: 10.1016/j.devcel.2007.02.020. PMID: 17419999.
  19. Grewal SS, Li L, Orian A, Eisenman RN, Edgar BA. Myc-dependent regulation of ribosomal RNA synthesis during Drosophila development. Nat Cell Biol. 2005;7:295-302. doi: 10.1038/ncb1223. PMID: 15723055.
  20. Reis T, Edgar BA. Negative regulation of dE2F1 by cyclin-dependent kinases controls cell cycle timing. Cell. 2004;16;117:253-64. doi: 10.1016/s0092-8674(04)00247-8. PMID: 15084262.
  21. Saucedo LJ, Gao X, Chiarelli DA, Li L, Pan D, Edgar BA. Rheb promotes cell growth as a component of the insulin/TOR signalling network. Nat Cell Biol. 2003 Jun;5(6):566-71. doi: 10.1038/ncb996. Erratum in: Nat Cell Biol. 2003 Jul;5(7):680. PMID: 12766776.
  22. Datar SA, Jacobs HW, de la Cruz AF, Lehner CF, Edgar BA. The Drosophila cyclin D-Cdk4 complex promotes cellular growth. EMBO J. 2000;1;19:4543-54. doi: 10.1093/emboj/19.17.4543. PMID: 10970848; PMCID: PMC302080.
  23. Prober DA, Edgar BA. Ras1 promotes cellular growth in the Drosophila wing. Cell. 2000;18;100:435-46. doi: 10.1016/s0092-8674(00)80679-0. PMID: 10693760.
  24. Johnston LA, Prober DA, Edgar BA, Eisenman RN, Gallant P. Drosophila myc regulates cellular growth during development. Cell. 1999;17;98:779-90. doi: 10.1016/s0092-8674(00)81512-3. PMID: 10499795.
  25. Neufeld TP, de la Cruz AF, Johnston LA, Edgar BA. Coordination of growth and cell division in the Drosophila wing. Cell. 1998;26;93:1183-93. doi: 10.1016/s0092-8674(00)81462-2. PMID: 9657151.
  26. Johnston LA, Edgar BA. Wingless and Notch regulate cell-cycle arrest in the developing Drosophila wing. Nature. 1998;2;394:82-4. doi: 10.1038/27925. PMID: 9665132.
  27. Britton JS, Edgar BA. Environmental control of the cell cycle in Drosophila: Nutrition activates mitotic and endoreplicative cells by distinct mechanisms. Development. 1998;125:2149-58. PMID: 9570778.
Last Updated: 7/31/23