Bruce A. Edgar

Bruce A. Edgar, PhD

Languages spoken: English

Academic Information

Departments Primary - Oncological Sciences , Adjunct - Human Genetics

Academic Office Information

Bruce.Edgar@hci.utah.edu

Lab

Research Interests

  • Cancer Biology
  • Cell Biology
  • Developmental Biology
  • Gene Expression
  • Cancer Genetics
  • Cell Growth and Proliferation
  • Drosophila melanogaster

Bruce Edgar (b1960) received a B.A. from Swarthmore College (1982), and a PhD in Genetics from the University of Washington (1987), where he studied with Gerold Schubiger. Dr. Edgar did postdoctoral work at UCSF and Oxford with Pat O’Farrell and Paul Nurse, respectively, and in 1993 started as an independent investigator at the Fred Hutchinson Cancer Research Center in Seattle.

From 2009-2016 he worked in Heidelberg, Germany, as a professor in the Center for Molecular Biology (ZMBH) and a division leader at the German Cancer Research Center (DKFZ). In 2016 Dr. Edgar moved his laboratory to the Huntsman Cancer Institute of the University of Utah. Since ~1986 Dr. Edgar’s research has used the Drosophila model system to study the control of cell growth and proliferation during development, tissue maintenance and tumorigenesis. A number of key cell cycle and growth regulatory genes have been identified and characterized, some of which play important roles in human disease, most notably cancer.

Current studies in Dr. Edgar’s lab focus on how the fly’s intestinal stem cells support regenerative growth, and how these stem cells can become tumorigenic.

Research Statement

Our Research

Our research focuses on the mechanisms that control cell growth and proliferation in the fruit fly, Drosophila melanogaster. The superlative genetic tools and fast life cycle of this tiny model organism make it a powerful system for discovery-based research, and its genetic similarity to humans makes much of what is discovered relevant to human biology and health. In the Edgar lab we use genetics to characterize the programs of cell growth and proliferation that occur during development, regeneration and tumorigenesis, with the goal of finding the genes that act as limiting regulators in each context. We furthermore seek to understand how networks of genes and communities of cells in a tissue function as integrated systems. Techniques in use in the lab range from classical and molecular genetics, to high resolution imaging, to whole genome gene expression profiling and RNAi screening.

Current projects in the lab fall in two areas. One set of projects focuses on the mechanisms of epithelial self-renewal in the intestine of the adult fly. A second set of projects addresses how G1/S progression – the initiation of DNA replication – is controlled by rates of cell growth and growth factor signaling. For both projects to overeaching goal is to define new mechanisms involved in growth control that are relevant to basic paradigms in cell and developmental biology, and to issues in human health such as cancer diagnosis and therapy, chronic inflammation, and regenerative medicine.

Epithelial renewal in the Drosophila intestine

Objective: To understand how cell-cell interactions, diet, the microbiota, and infection regulate the proliferation of intestinal stem cells, facilitating tissue self-renewal in healthy animals and, in tumor models, a loss of growth control.

Overview: Like mammals, insects have intestinal stem cells (ISCs) that drive dynamic self-renewal of the gut epithelium. The simplicity of the Drosophila midgut and the superior genetic tools available make this an attractive model for studies of stem cell biology and gut homeostasis. Cellular and molecular similarities to the human gut suggest relevance to diseases like colorectal cancer and inflammatory bowel disease. In exploring how ISC division is controlled, we discovered that damage to the intestinal epithelium results in a burst of stem cell division that facilitates rapid regeneration. To understand this regenerative response we have analyzed the functions of most of the major signaling pathways in each of the five intestinal cell types. We discovered that gut epithelial stress or damage induces JNK and p38-Map Kinase activity and suppresses Hippo signaling in epithelial enterocytes (ECs), and that this triggers the production of secreted cytokines (upd2, upd3) and EGFR ligands (Vn, Spi, Krn) that stimulate JAK/STAT and Ras/MAPK activity in the intestinal stem cells, activating them to grow and divide.

Approach: Our elucidation of a feedback system explaining gut homeostasis highlights new areas of research that can enhance our understanding of tissue biology and human disease. These include: how damage is sensed by the gut epithelium, how stress signaling activates growth factor and cytokine signaling and inflammation, how growth factor signaling activates stem cells, and how transformed stem cells develop into tumors and subvert the mechanisms that mediate normal gut homeostasis. Our understanding of the intestinal stem cell niche, how stem cell pools are controlled, and how differentiation is coordinated with ISC division is also incomplete. Classic questions in cell biology, such as how growth factor signaling activates cell growth and the cell cycle machinery, also remain insufficiently answered, and ripe for study in this system. Projects addressing each of these questions are currently underway in the lab.

Ongoing Research

1: How is gut epithelial damage sensed? When gut enterocytes (EC) are damaged or lost, the surrounding epithelium responds by producing IL-6- Leptin-like cytokines (Upd2, Upd2), which trigger a signaling cascade that activates ISCs to grow, divide, and produce new ECs. Our understanding of this damage response is so rudimentary that we don’t even know if the intial signals are chemical or mechanical. To identify the genes and pathways the gut uses to sense damage and trigger Upd3 expression, we are testing candidate pathways (Jnk, p38, Hpo) and processes (Ca++, ROS signaling), and performing a genome-scale RNAi screen. Genes found to be essential for damage sensing will be characterized and assigned to regulatory pathways. The results should yield general insight into how epithelial integrity is maintained, and how dysfuntion in damage sensing systems contributes to losses in epithelial homeostasis that lead to diseases like chronic inflammation and cancer.

2: How does EGFR signaling activate ISC proliferation? Signaling via the epidermal growth factor receptor (EGFR), Ras, and the mitogen activated protein kinase (MapK) is required and sufficient for ISC activation downstream of gut epithelial damage. Although intensively studied and central to an overwhelming number of cancers, how Ras/Mapk signaling actually drives cell growth and division is surprisingly poorly understood. We recently identified the transcriptional repressor Capicua (Cic) and two of its targets, the ETS transcription factors Pnt and Ets21C, as critical Ras-dependent effectors of ISC activation. Each of these genes is associated with human cancer, most likely as effectors of the Ras oncogene. Our current studies combine target gene identification with functional tests to determine the mechanisms by which these transcription factors activate ISC growth and division. We are also testing whether there are Cic- and ETS-independent functions of MapK signaling, and if there are, we will undertake to identify the critical targets.

3: What niche and host factors support the growth of ISC-derived tumors? We developed a tumor model in which intestinal stem cells expressing a differentiation inhibitor (NotchRNAi) and an EGFR signaling activator (RasV12G, RafAct, Pnt, Ers21C, or CicRNAi) generate rapidly growing tumors that can be serially transplanted in flies. After transplantation these aggressive tumors grow rapidly in many parts of the fly, recruit trachea, and kill the host. A gene replacement strategy is being used to determine the functions required to allow niche-independent stem cell tumor growth. Using genetically modified hosts, are also testing the requirement from the host animal, checking processes such as cell adhesion, epithelial tension, oxygen supply, blood cells, and nutrition, in niche-independent tumor growth. An RNAseq screen will also be used to identify other potentially relevant host processes. We hope to determine the full catalog of factors and conditions required for transformed ISCs to grow outside the stem cell niche.

4: Can ISC proliferation and differentiation be recapitulated in vitro? The lack of long-term primary cell or organ culture remains a major limitation to Drosophila as a model system for research. We are attempting to develop primary culture of Drosophila intestinal stem cells (ISCs) by testing combinations of genetic manipulations and culture conditions. A protocol for culturing ISCs will allow many new approaches for studying stem cell biology. These include live analysis of cell proliferation, lineage asymmetry and differentiation, cell-based RNAi screening, and molecular techniques like RNAseq, ChIP, and protein mass spectrometry that work best with large numbers of synchronous homogeneous cells.

Growth-dependent control of the Cell Cycle

Objective: To understand how the initiation of DNA replication (G1/S transition) is coordinated with rates of cell growth and controlled by growth factor signaling.

Overview: In growing animal cells, rates of cell cycle progression are usually tightly coupled to rates of cell growth (mass accumulation), such that cells divide each time they double their mass. The growth of animal cells is limited by nutrition via TOR signaling, and also regulated by signaling through receptor tyrosine kinases, cytokine receptors, and G-protein coupled-receptors. Genes in all of these pathways are highly associated with cancer development, and can be targeted for cancer therapy. A central question in cell biology is how growth factor signaling via these conduits controls the cell cycle. Many studies, both classic ones using human cells and from our lab using the Drosophila system, indicate that growth-coupled cell cycle control is executed principally at G1àS rather than G2àM transitions. Studies with human cells have engendered a model, depicted in many textbooks, wherein growth factor signaling triggers phosphorylation cascades that lead to the transcriptional activation of genes encoding G1 Cyclin-dependent Kinase (Cdk) complexes, which in turn trigger DNA replication. However our studies in Drosophila, as well as many studies from mice and yeast, do not support central aspects of this model. Instead, we suggest an alternative mechanism wherein translational regulation of limiting cell cycle regulators determines rates of G1àS progression.

We have been researching this issue using endocycling cells of the Drosophila gut and salivary glands. Endocycles consist of DNA Synthesis (S) and Gap phases (G) without intervening Mitoses (M). In most endoreplicating cells nutrition-dependent Insulin/TOR signaling is the principle driver of cell growth and DNA replication, but other inputs such as EGFR/MAPK signaling can also have important growth promoting functions. In 2011 we reported that the fly’s endocycles employ a novel bi-phasic oscillator in which the transcription factor E2F1 promotes cyclin E (cycE) transcription, CycE/Cdk2 then triggers S-phase, and S-phase in turn causes the destruction of E2F1 by activating a DNA-replication specific ubiquitin ligase, CRL4cdt2. Strikingly, factors that alter protein synthetic rates such as nutrition, TOR or Ras activity regulate E2F protein levels and thereby make endocycle progression growth-dependent. Our tests indicated that E2F protein levels in this context are controlled translationally, suggesting that translational efficiency provides the “missing link” between cell growth and G1àS progression in Drosophila. Recent studies in our lab indicate that in another endoreplicating cell type, the midgut Enteroblast (EB), EGFR/Ras/MapK signaling drives endocycling, also via translational control of E2F1. Notably, the mechanism we propose need not be relevant only to endocycles, but potentially controls G0 and/or G1 length in proliferating diploid cells.

Approach: Our ongoing studies have two goals. First, we are testing our translational model for coupling cell growth to G1àS progression, using reporter mRNAs derived from E2F1 and alterations in signaling and nutrition to modulate translation. Our intention is to confirm the translational model, define the mRNA sequences that mediate translational efficiency, and determine how they do this. Second, we would like to know which elements of the endocycle mechanism we’ve elucidated in Drosophila are conserved in mammalian cell cycles and in G1àS control in general. To investigate the question of conservation we are assaying the periodicity of tagged human E2F proteins, and their dependence on CRL4Cdt2, in cultured human cells.

Ongoing Research:

1: Translational control of E2F1. To further validate our model for G1àS control, we are characterizing the serum- Ras-, and TOR-dependent translational control of a set of E2F 5’UTR reporters. If these tests show that E2F 5’ UTRs mediate E2F translation, we will create further 5’ UTR deletion constructs to fine-map the mRNA sequences responsible (these will be translation suppression sequences). Then, CRISPR technology will be used to mutate these regulatory sites in the E2F locus in cells and flies, and their cell cycle progression phenotypes will be assayed. We expect such mutants to have shortened G1 periods, and to show some degree of growth factor- and nutrition-independence for G1àS progression. Using the E2F 5’ UTR elements defined above, we will screen for upstream translational regulators.

2: How does EGFR/MAPK signaling drive cell growth? EGFR/RAS/MAPK signaling drives the growth of many types of animal cells, most notably cancer cells transformed by activated mutant forms of RAS, RAF, NF2, ErbB2, and EGFR. It’s amazing that we don’t understand how this signaling pathway drives cell growth, but it clearly does. In Drosophila, the most profound growth effects we’ve discovered are in the adult intestinal stem cells (ISCs), Enteroblasts and their progenitors, the larval “Adult Midgut Progenitor” cells (AMPs). We are taking a multi-faceted approach to determine how EGFR signaling makes these cells grow. Epistasis tests are being used to test candidate downstream effectors such as RSK, AKT, and TOR components, and transcriptome and proteome profiling is being performed to identify potential targets.

3: Translational control of mitotic cycles via E2F1. Although most of our work has focused on endocycling cells, we believe that the cell cycle ingrowing mitotic cells is also highly subject to translational control. To test this theory, we are evaluating Drosophila E2F1 as a growth sensor in two mitotic cell types: wing progenitors and intestinal stem cells. In these experiments we alter oncogenic growth signaling (Myc, PI3K, Ras, Tor, Hpo) and measure how this affects levels of E2F1 protein, mRNA, and rates of cell division. If the results support translational control, the specific mechanism will be sought using E2F1-UTR mutants and trans-acting factors identified as above. These experiments will provide examples of how a growth sensor regulates proliferation in stem and progenitor cells, further validating the mechanism’s relevance to development and human disease.

4: Do human cells use growth-sensing cell cycle regulators? Answering this question could revise a central, cancer-relevant paradigm in cell biology and present new strategies for cellular growth control. In this project we are using ribosome profiling of normal human epithelial cells (RPE-1) to identify growth factor-dependent, translationally regulated genes that potentially regulate the cell cycle. Candidate genes so defined will be functionally tested to determine whether they actually regulate cell proliferation. Using ribosome density maps, we will address specific mechanisms of translational control and how these interface with growth and growth factor signaling.

Education History

Doctoral Training University of Washington
 PhD
Swarthmore College
 BA

Selected Publications

Journal Article

  1. Marchetti M, Zhang C, Edgar BA (2022). An improved organ explant culture method reveals stem cell lineage dynamics in the adult Drosophila intestine. Elife, 11. (Read full article)
  2. Zhang C, Jin Y, Marchetti M, Lewis MR, Hammouda OT, Edgar BA (2022). EGFR signaling activates intestinal stem cells by promoting mitochondrial biogenesis and β-oxidation. Curr Biol, 32, 3704-3719.e7. (Read full article)
  3. vreb JI, Bradley-Gill MR, Zielke N, Kim M, Marchetti M, Bohlen J, Lewis M, van Straaten M, Moon NS, Edgar BA (2021). Translational control of E2f1 regulates the Drosophila cell cycle. Proc Natl Acad Sci U S A, 119(4). (Read full article)
  4. Tamamouna V, Rahman MM, Petersson M, Charalambous I, Kux K, Mainor H, Bolender V, Isbilir B, Edgar BA, Pitsouli C (2021). Remodelling of oxygen-transporting tracheoles drives intestinal regeneration and tumorigenesis in Drosophila. Nat Cell Biol, 23(5), 497-510. (Read full article)
  5. Tauc HM, Rodriguez-Fernandez IA, Hackney JA, Pawlak M, Ronnen Oron T, Korzelius J, Moussa HF, Chaudhuri S, Modrusan Z, Edgar BA, Jasper H (2021). Age-related changes in polycomb gene regulation disrupt lineage fidelity in intestinal stem cells. Elife, 10. (Read full article)
  6. Zhang P, Katzaroff AJ, Buttitta LA, Ma Y, Jiang H, Nickerson DW, vreb JI, Edgar BA (2021). The Krüppel-like factor Cabut has cell cycle regulatory properties similar to E2F1. Proc Natl Acad Sci U S A, 118(7). (Read full article)
  7. Ahmed SMH, Maldera JA, Krunic D, Paiva-Silva GO, Pnalva C, Teleman AA, Edgar BA (2020). Fitness trade-offs incurred by ovary-to-gut steroid signalling in Drosophila. Nature, 584(7821), 415-419. (Read full article)
  8. Kwon YV, Zhao B, Xu C, Lee J, Chen CL, Vinayagam A, Edgar BA, Perrimon N (2019). The role of translationally controlled tumor protein in proliferation of Drosophila intestinal stem cells. Proc Natl Acad Sci U S A, 116, 26591-26598. (Read full article)
  9. Patel PH, Pnalva C, Kardorff M, Roca M, Pavlovi B, Thiel A, Teleman AA, Edgar BA (2019). Damage sensing by a Nox-Ask1-MKK3-p38 signaling pathway mediates regeneration in the adult Drosophila midgut. Nat Commun, 10(1), 4365. (Read full article)
  10. Zhang P, Holowatyj AN, Roy T, Pronovost SM, Marchetti M, Liu H, Ulrich CM, Edgar BA (2019). An SH3PX1-Dependent Endocytosis-Autophagy Network Restrains Intestinal Stem Cell Proliferation by Counteracting EGFR-ERK Signaling. Dev Cell, 49(4), 574-589.e5. (Read full article)
  11. Oberacker T, Bajorat J, Ziola S, Schroeder A, Rth D, Kastl L, Edgar BA, Wagner W, Glow K, Krammer PH (2018). Enhanced expression of thioredoxin-interacting-protein regulates oxidative DNA damage and aging. FEBS Lett, 592(13), 2297-2307. (Read full article)
  12. Garca Del Arco A, Edgar BA, Erhardt S (2018). In Vivo Analysis of Centromeric Proteins Reveals a Stem Cell-Specific Asymmetry and an Essential Role in Differentiated, Non-proliferating Cells. Cell Rep, 22(8), 1982-1993. (Read full article)
  13. Zhang P, Pei C, Wang X, Xiang J, Sun BF, Cheng Y, Qi X, Marchetti M, Xu JW, Sun YP, Edgar BA, Yuan Z (2017). A Balance of Yki/Sd Activator and E2F1/Sd Repressor Complexes Controls Cell Survival and Affects Organ Size. Dev Cell, 43(5), 603-617.e5. (Read full article)
  14. Jin Y, Patel PH, Kohlmaier A, Pavlovic B, Zhang C, Edgar BA (2017). Intestinal Stem Cell Pool Regulation in Drosophila. Stem Cell Reports, 8(6), 1479-1487. (Read full article)
  15. Xiang J, Bandura J, Zhang P, Jin Y, Reuter H, Edgar BA (2017). EGFR-dependent TOR-independent endocycles support Drosophila gut epithelial regeneration. Nat Commun, 8, 15125. (Read full article)
  16. Zhou J, Edgar BA, Boutros M (2017). ATF3 acts as a rheostat to control JNK signalling during intestinal regeneration. Nat Commun, 8, 14289. (Read full article)
  17. Strilbytska OM, Semaniuk UV, Storey KB, Edgar BA, Lushchak OV (2017). Activation of the Tor/Myc signaling axis in intestinal stem and progenitor cells affects longevity, stress resistance and metabolism in drosophila. Comp Biochem Physiol B Biochem Mol Biol, 203, 92-99. (Read full article)
  18. Zielke N, van Straaten M, Bohlen J, Edgar BA (2016). Using the Fly-FUCCI System for the Live Analysis of Cell Cycle Dynamics in Cultured Drosophila Cells. Methods Mol Biol, 1342, 305-20. (Read full article)
  19. Jin Y, Ha N, Fors M, Xiang J, Gler C, Maldera J, Jimnez G, Edgar BA (2015). EGFR/Ras Signaling Controls Drosophila Intestinal Stem Cell Proliferation via Capicua-Regulated Genes. PLoS Genet, 11(12), e1005634. (Read full article)
  20. Icreverzi, A, de la Cruz, AFA, Edgar, BA (2015). Changes in neuronal CycD/Cdk4 activity affect aging, neurodegeneration, and oxidative stress. Aging Cell, 14(5), 896-906.
  21. Icreverzi A, de la Cruz AF, Walker DW, Edgar BA (2015). Changes in neuronal CycD/Cdk4 activity affect aging, neurodegeneration, and oxidative stress. Aging Cell, 14(5), 896-906. (Read full article)
  22. Patel PH, Dutta D, Edgar BA (2015). Niche appropriation by Drosophila intestinal stem cell tumours. Nat Cell Biol, 17(9), 1182-92. (Read full article)
  23. Dutta D, Buchon N, Xiang J, Edgar BA (2015). Regional Cell Specific RNA Expression Profiling of FACS Isolated Drosophila Intestinal Cell Populations. Curr Protoc Stem Cell Biol, 34, 2F.2.1-14. (Read full article)
  24. Dutta D, Dobson AJ, Houtz PL, Gler C, Revah J, Korzelius J, Patel PH, Edgar BA, Buchon N (2015). Regional Cell-Specific Transcriptome Mapping Reveals Regulatory Complexity in the Adult Drosophila Midgut. Cell Rep, 12(2), 346-58. (Read full article)
  25. Kohlmaier A, Fassnacht C, Jin Y, Reuter H, Begum J, Dutta D, Edgar BA (2015). Src kinase function controls progenitor cell pools during regeneration and tumor onset in the Drosophila intestine. Oncogene, 34(18), 2371-84. (Read full article)
  26. Zhou J, Florescu S, Boettcher AL, Luo L, Dutta D, Kerr G, Cai Y, Edgar BA, Boutros M (2015). Dpp/Gbb signaling is required for normal intestinal regeneration during infection. Dev Biol, 399(2), 189-203. (Read full article)
  27. Korzelius J, Naumann SK, Loza-Coll MA, Chan JS, Dutta D, Oberheim J, Gler C, Southall TD, Brand AH, Jones DL, Edgar BA (2014). Escargot maintains stemness and suppresses differentiation in Drosophila intestinal stem cells. EMBO J, 33(24), 2967-82. (Read full article)
  28. Bajorat J, Oberacker T, Ziola S, Edgar BA, Glow K, Krammer PH (2014). AF-1 a novel regulator of the redox equilibrium during aging. Free Radic Biol Med, 75 Suppl 1, S22-3. (Read full article)
  29. OKeefe DD, Thomas S, Edgar BA, Buttitta L (2014). Temporal regulation of Dpp signaling output in the Drosophila wing. Dev Dyn, 243(6), 818-32. (Read full article)
  30. Zielke N, Korzelius J, van Straaten M, Bender K, Schuhknecht GFP, Dutta D, Xiang J, Edgar BA (2014). Fly-FUCCI: A versatile tool for studying cell proliferation in complex tissues. Cell Rep, 7(2), 588-598. (Read full article)
  31. Song M, Zhang Y, Katzaroff AJ, Edgar BA, Buttitta L (2014). Hunting complex differential gene interaction patterns across molecular contexts. Nucleic Acids Res, 42(7), e57. (Read full article)
  32. Dutta D, Xiang J, Edgar BA (2013). RNA expression profiling from FACS-isolated cells of the Drosophila intestine. Curr Protoc Stem Cell Biol, 27, Unit 2F.2.. (Read full article)
  33. Kuo Y, Ren S, Lao U, Edgar BA, Wang T (2013). Suppression of polyglutamine protein toxicity by co-expression of a heat-shock protein 40 and a heat-shock protein 110. Cell Death Dis, 4, e833. (Read full article)
  34. Doumpas N, Ruiz-Romero M, Blanco E, Edgar B, Corominas M, Teleman AA (2013). Brk regulates wing disc growth in part via repression of Myc expression. EMBO Rep, 14(3), 261-8. (Read full article)
  35. Bandura JL, Jiang H, Nickerson DW, Edgar BA (2013). The molecular chaperone Hsp90 is required for cell cycle exit in Drosophila melanogaster. PLoS Genet, 9(9), e1003835. (Read full article)
  36. OKeefe DD, Thomas SR, Bolin K, Griggs E, Edgar BA, Buttitta LA (2012). Combinatorial control of temporal gene expression in the Drosophila wing by enhancers and core promoters. BMC Genomics, 13, 498. (Read full article)
  37. OKeefe DD, Gonzalez-Nio E, Edgar BA, Curtiss J (2012). Discontinuities in Rap1 activity determine epithelial cell morphology within the developing wing of Drosophila. Dev Biol, 369(2), 223-34. (Read full article)
  38. Wang T, Blumhagen R, Lao U, Kuo Y, Edgar BA (2012). LST8 regulates cell growth via target-of-rapamycin complex 2 (TORC2). Mol Cell Biol, 32(12), 2203-13. (Read full article)
  39. Icreverzi A, de la Cruz AF, Van Voorhies WA, Edgar BA (2012). Drosophila cyclin D/Cdk4 regulates mitochondrial biogenesis and aging and sensitizes animals to hypoxic stress. Cell Cycle, 11(3), 554-68. (Read full article)
  40. Brown HL, Kaun KR, Edgar BA (2012). The small GTPase Rheb affects central brain neuronal morphology and memory formation in Drosophila. PLoS One, 7(9), e44888. (Read full article)
  41. 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 (2011). Control of Drosophila endocycles by E2F and CRL4(CDT2). Nature, 480(7375), 123-7. (Read full article)
  42. Jiang H, Grenley MO, Bravo MJ, Blumhagen RZ, Edgar BA (2011). EGFR/Ras/MAPK signaling mediates adult midgut epithelial homeostasis and regeneration in Drosophila. Cell Stem Cell, 8(1), 84-95. (Read full article)
  43. OKeefe DD, Edgar BA, Saucedo LJ (2011). EndoGI modulates Notch signaling and axon guidance in Drosophila. Mech Dev, 128(1-2), 59-70. (Read full article)
  44. Shaw RL, Kohlmaier A, Polesello C, Veelken C, Edgar BA, Tapon N (2010). The Hippo pathway regulates intestinal stem cell proliferation during Drosophila adult midgut regeneration. Development, 137(24), 4147-58. (Read full article)
  45. Buttitta LA, Katzaroff AJ, Edgar BA (2010). A robust cell cycle control mechanism limits E2F-induced proliferation of terminally differentiated cells in vivo. J Cell Biol, 189(6), 981-96. (Read full article)
  46. Li L, Edgar BA, Grewal SS (2010). Nutritional control of gene expression in Drosophila larvae via TOR, Myc and a novel cis-regulatory element. BMC Cell Biol, 11, 7. (Read full article)
  47. Wang T, Lao U, Edgar BA (2009). TOR-mediated autophagy regulates cell death in Drosophila neurodegenerative disease. J Cell Biol, 186(5), 703-11. (Read full article)
  48. OKeefe DD, Gonzalez-Nio E, Burnett M, Dylla L, Lambeth SM, Licon E, Amesoli C, Edgar BA, Curtiss J (2009). Rap1 maintains adhesion between cells to affect Egfr signaling and planar cell polarity in Drosophila. Dev Biol, 333(1), 143-60. (Read full article)
  49. Jiang H, Patel PH, Kohlmaier A, Grenley MO, McEwen DG, Edgar BA (2009). Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell, 137(7), 1343-55. (Read full article)
  50. Jiang H, Edgar BA (2009). EGFR signaling regulates the proliferation of Drosophila adult midgut progenitors. Development, 136(3), 483-93. (Read full article)
  51. Joe Song M, Hong CC, Zhang Y, Buttitta L, Edgar BA (2009). Comparative Generalized Logic Modeling Reveals Differential Gene Interactions during Cell Cycle Exit in Drosophila Wing Development. GI Ed Proc, 157, 143-152. (Read full article)
  52. Shibutani ST, de la Cruz AF, Tran V, Turbyfill WJ 3rd, Reis T, Edgar BA, Duronio RJ (2008). Intrinsic negative cell cycle regulation provided by PIP box- and Cul4Cdt2-mediated destruction of E2f1 during S phase. Dev Cell, 15(6), 890-900. (Read full article)
  53. Oren-Giladi P, Krieger O, Edgar BA, Chamovitz DA, Segal D (2008). Cop9 signalosome subunit 8 (CSN8) is essential for Drosophila development. Genes Cells, 13(3), 221-31. (Read full article)
  54. Grewal SS, Evans JR, Edgar BA (2007). Drosophila TIF-IA is required for ribosome synthesis and cell growth and is regulated by the TOR pathway. J Cell Biol, 179(6), 1105-13. (Read full article)
  55. OKeefe DD, Prober DA, Moyle PS, Rickoll WL, Edgar BA (2007). Egfr/Ras signaling regulates DE-cadherin/Shotgun localization to control vein morphogenesis in the Drosophila wing. Dev Biol, 311(1), 25-39. (Read full article)
  56. Buttitta LA, Katzaroff AJ, Perez CL, de la Cruz A, Edgar BA (2007). A double-assurance mechanism controls cell cycle exit upon terminal differentiation in Drosophila. Dev Cell, 12(4), 631-43. (Read full article)
  57. Hall DJ, Grewal SS, de la Cruz AF, Edgar BA (2007). Rheb-TOR signaling promotes protein synthesis, but not glucose or amino acid import, in Drosophila. BMC Biol, 5, 10. (Read full article)
  58. Oron E, Tuller T, Li L, Rozovsky N, Yekutieli D, Rencus-Lazar S, Segal D, Chor B, Edgar BA, Chamovitz DA (2007). Genomic analysis of COP9 signalosome function in Drosophila melanogaster reveals a role in temporal regulation of gene expression. Mol Syst Biol, 3, 108. (Read full article)
  59. Datar SA, Galloni M, de la Cruz A, Marti M, Edgar BA, Frei C (2006). Mammalian cyclin D1/Cdk4 complexes induce cell growth in Drosophila. Cell Cycle, 5(6), 647-52. (Read full article)
  60. Loo LW, Secombe J, Little JT, Carlos LS, Yost C, Cheng PF, Flynn EM, Edgar BA, Eisenman RN (2005). The transcriptional repressor dMnt is a regulator of growth in Drosophila melanogaster. Mol Cell Biol, 25(16), 7078-91. (Read full article)
  61. Grewal SS, Li L, Orian A, Eisenman RN, Edgar BA (2005). Myc-dependent regulation of ribosomal RNA synthesis during Drosophila development. Nat Cell Biol, 7(3), 295-302. (Read full article)
  62. Frei C, Galloni M, Hafen E, Edgar BA (2005). The Drosophila mitochondrial ribosomal protein mRpL12 is required for Cyclin D/Cdk4-driven growth. EMBO J, 24(3), 623-34. (Read full article)
  63. Orian A, Grewal SS, Knoepfler PS, Edgar BA, Parkhurst SM, Eisenman RN (2005). Genomic binding and transcriptional regulation by the Drosophila Myc and Mnt transcription factors. Cold Spring Harb Symp Quant Biol, 70, 299-307. (Read full article)
  64. Emmerich J, Meyer CA, de la Cruz AF, Edgar BA, Lehner CF (2004). Cyclin D does not provide essential Cdk4-independent functions in Drosophila. Genetics, 168(2), 867-75. (Read full article)
  65. Pierce SB, Yost C, Britton JS, Loo LW, Flynn EM, Edgar BA, Eisenman RN (2004). dMyc is required for larval growth and endoreplication in Drosophila. Development, 131(10), 2317-27. (Read full article)
  66. Reis T, Edgar BA (2004). Negative regulation of dE2F1 by cyclin-dependent kinases controls cell cycle timing. Cell, 117(2), 253-64. (Read full article)
  67. Frei C, Edgar BA (2004). Drosophila cyclin D/Cdk4 requires Hif-1 prolyl hydroxylase to drive cell growth. Dev Cell, 6(2), 241-51. (Read full article)
  68. Zhang Y, Gao X, Saucedo LJ, Ru B, Edgar BA, Pan D (2003). Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. Nat Cell Biol, 5(6), 578-81. (Read full article)
  69. Saucedo LJ, Gao X, Chiarelli DA, Li L, Pan D, Edgar BA (2003). Rheb promotes cell growth as a component of the insulin/TOR signalling network. Nat Cell Biol, 5(6), 566-71. (Read full article)
  70. Orian A, van Steensel B, Delrow J, Bussemaker HJ, Li L, Sawado T, Williams E, Loo LW, Cowley SM, Yost C, Pierce S, Edgar BA, Parkhurst SM, Eisenman RN (2003). Genomic binding by the Drosophila Myc, Max, Mad/Mnt transcription factor network. Genes Dev, 17(9), 1101-14. (Read full article)
  71. Prober DA, Edgar BA (2002). Interactions between Ras1, dMyc, and dPI3K signaling in the developing Drosophila wing. Genes Dev, 16(17), 2286-99. (Read full article)
  72. Martn-Castellanos C, Edgar BA (2002). A characterization of the effects of Dpp signaling on cell growth and proliferation in the Drosophila wing. Development, 129(4), 1003-13. (Read full article)
  73. Britton JS, Lockwood WK, Li L, Cohen SM, Edgar BA (2002). Drosophila's insulin/PI3-kinase pathway coordinates cellular metabolism with nutritional conditions. Dev Cell, 2(2), 239-49. (Read full article)
  74. Frank DJ, Edgar BA, Roth MB (2002). The Drosophila melanogaster gene brain tumor negatively regulates cell growth and ribosomal RNA synthesis. Development, 129(2), 399-407. (Read full article)
  75. Datar SA, Jacobs HW, de la Cruz AF, Lehner CF, Edgar BA (2000). The Drosophila cyclin D-Cdk4 complex promotes cellular growth. EMBO J, 19(17), 4543-54. (Read full article)
  76. Meyer CA, Jacobs HW, Datar SA, Du W, Edgar BA, Lehner CF (2000). Drosophila Cdk4 is required for normal growth and is dispensable for cell cycle progression. EMBO J, 19(17), 4533-42. (Read full article)
  77. Prober DA, Edgar BA (2000). Ras1 promotes cellular growth in the Drosophila wing. Cell, 100(4), 435-46. (Read full article)
  78. Johnston LA, Prober DA, Edgar BA, Eisenman RN, Gallant P (1999). Drosophila myc regulates cellular growth during development. Cell, 98(6), 779-90. (Read full article)
  79. Migeon JC, Garfinkel MS, Edgar BA (1999). Cloning and characterization of peter pan, a novel Drosophila gene required for larval growth. Mol Biol Cell, 10(6), 1733-44. (Read full article)
  80. Galloni M, Edgar BA (1999). Cell-autonomous and non-autonomous growth-defective mutants of Drosophila melanogaster. Development, 126(11), 2365-75. (Read full article)
  81. Lehman DA, Patterson B, Johnston LA, Balzer T, Britton JS, Saint R, Edgar BA (1999). Cis-regulatory elements of the mitotic regulator, string/Cdc25. Development, 126(9), 1793-803. (Read full article)
  82. Johnston LA, Edgar BA (1998). Wingless and Notch regulate cell-cycle arrest in the developing Drosophila wing. Nature, 394(6688), 82-4. (Read full article)
  83. Neufeld TP, de la Cruz AF, Johnston LA, Edgar BA (1998). Coordination of growth and cell division in the Drosophila wing. Cell, 93(7), 1183-93. (Read full article)
  84. Britton JS, Edgar BA (1998). Environmental control of the cell cycle in Drosophila: nutrition activates mitotic and endoreplicative cells by distinct mechanisms. Development, 125(11), 2149-58. (Read full article)
  85. Edgar BA, Datar SA (1996). Zygotic degradation of two maternal Cdc25 mRNAs terminates Drosophila's early cell cycle program. Genes Dev, 10(15), 1966-77. (Read full article)
  86. Campbell SD, Sprenger F, Edgar BA, OFarrell PH (1995). Drosophila Wee1 kinase rescues fission yeast from mitotic catastrophe and phosphorylates Drosophila Cdc2 in vitro. Mol Biol Cell, 6(10), 1333-47. (Read full article)
  87. Edgar BA, Lehman DA, OFarrell PH (1994). Transcriptional regulation of string (cdc25): a link between developmental programming and the cell cycle. Development, 120(11), 3131-43. (Read full article)
  88. Edwards KA, Montague RA, Shepard S, Edgar BA, Erikson RL, Kiehart DP (1994). Identification of Drosophila cytoskeletal proteins by induction of abnormal cell shape in fission yeast. Proc Natl Acad Sci U S A, 91(10), 4589-93. (Read full article)
  89. Edgar BA, Sprenger F, Duronio RJ, Leopold P, OFarrell PH (1994). Distinct molecular mechanism regulate cell cycle timing at successive stages of Drosophila embryogenesis. Genes Dev, 8(4), 440-52. (Read full article)
  90. Moreno S, Edgar BA, Nurse P (1994). Regulation of progression through the G1 phase of the cell cycle by the rum1+ gene. Nature, 367, 236-42.
  91. Edgar BA, OFarrell PH (1990). The three postblastoderm cell cycles of Drosophila embryogenesis are regulated in G2 by string. Cell, 62(3), 469-80. (Read full article)
  92. Edgar BA, OFarrell PH (1989). Genetic control of cell division patterns in the Drosophila embryo. Cell, 57(1), 177-87. (Read full article)
  93. Edgar BA, Odell GM, Schubiger G (1989). A genetic switch, based on negative regulation, sharpens stripes in Drosophila embryos. Dev Genet, 10(3), 124-42. (Read full article)
  94. Weir MP, Edgar BA, Kornberg T, Schubiger G (1988). Spatial regulation of engrailed expression in the Drosophila embryo. Genes Dev, 2(9), 1194-203. (Read full article)
  95. Edgar BA, Odell GM, Schubiger G (1987). Cytoarchitecture and the patterning of fushi tarazu expression in the Drosophila blastoderm. Genes Dev, 1(10), 1226-37. (Read full article)
  96. Shinedling S, Singer BS, Gayle M, Pribnow D, Jarvis E, Edgar B, Gold L (1987). Sequences and studies of bacteriophage T4 rII mutants. J Mol Biol, 195(3), 471-80. (Read full article)
  97. Edgar BA, Weir MP, Schubiger G, Kornberg T (1986). Repression and turnover pattern fushi tarazu RNA in the early Drosophila embryo. Cell, 47(5), 747-54. (Read full article)
  98. Edgar BA, Schubiger G (1986). Parameters controlling transcriptional activation during early Drosophila development. Cell, 44(6), 871-7. (Read full article)
  99. Edgar BA, Kiehle CP, Schubiger G (1986). Cell cycle control by the nucleo-cytoplasmic ratio in early Drosophila development. Cell, 44(2), 365-72. (Read full article)
  100. Payvar F, DeFranco D, Firestone GL, Edgar B, Wrange O, Okret S, Gustafsson JA, Yamamoto KR (1983). Sequence-specific binding of glucocorticoid receptor to MTV DNA at sites within and upstream of the transcribed region. Cell, 35(2 Pt 1), 381-92. (Read full article)

Review

  1. vreb JI, Ma Y, Edgar BA (2022). Cell growth and the cell cycle: New insights about persistent questions. [Review]. Bioessays, 44(11), e2200150. (Read full article)
  2. Ovrebo JI, Edgar BA (2018). Polyploidy in tissue homeostasis and regeneration.LID - dev156034 [pii]LID - 10.1242/dev.156034 [doi]. [Review]. Development, 145(14). (Read full article)
  3. Edgar BA, Zielke N, Gutierrez C (2014). Endocycles: a recurrent evolutionary innovation for post-mitotic cell growth. [Review]. Nat Rev Mol Cell Biol, 15(3), 197-210. (Read full article)
  4. Jiang H, Edgar BA (2012). Intestinal stem cell function in Drosophila and mice. [Review]. Curr Opin Genet Dev, 22(4), 354-60. (Read full article)
  5. Jiang H, Edgar BA (2011). Intestinal stem cells in the adult Drosophila midgut. [Review]. Exp Cell Res, 317(19), 2780-8. (Read full article)
  6. Kohlmaier A, Edgar BA (2008). Proliferative control in Drosophila stem cells. [Review]. Curr Opin Cell Biol, 20(6), 699-706. (Read full article)
  7. Buttitta LA, Edgar BA (2007). Mechanisms controlling cell cycle exit upon terminal differentiation. [Review]. Curr Opin Cell Biol, 19(6), 697-704. (Read full article)
  8. Buttitta LA, Edgar BA (2007). How size is controlled: from Hippos to Yorkies. [Review]. Nat Cell Biol, 9(11), 1225-7. (Read full article)
  9. Saucedo LJ, Edgar BA (2007). Filling out the Hippo pathway. [Review]. Nat Rev Mol Cell Biol, 8(8), 613-21. (Read full article)
  10. Edgar BA (2006). How flies get their size: genetics meets physiology. [Review]. Nat Rev Genet, 7(12), 907-16. (Read full article)
  11. Edgar BA (2006). From cell structure to transcription: Hippo forges a new path. [Review]. Cell, 124(2), 267-73. (Read full article)
  12. Grewal SS, Edgar BA (2003). Controlling cell division in yeast and animals: does size matter? [Review]. J Biol, 2(1), 5. (Read full article)
  13. Saucedo LJ, Edgar BA (2002). Why size matters: altering cell size. [Review]. Curr Opin Genet Dev, 12(5), 565-71. (Read full article)
  14. Edgar BA, Orr-Weaver TL (2001). Endoreplication cell cycles: more for less. [Review]. Cell, 105(3), 297-306. (Read full article)
  15. Prober DA, Edgar BA (2001). Growth regulation by oncogenes--new insights from model organisms. [Review]. Curr Opin Genet Dev, 11(1), 19-26. (Read full article)
  16. Edgar BA (1999). From small flies come big discoveries about size control. [Review]. Nat Cell Biol, 1(8), E191-3. (Read full article)
  17. Neufeld TP, Edgar BA (1998). Connections between growth and the cell cycle. [Review]. Curr Opin Cell Biol, 10(6), 784-90. (Read full article)
  18. Edgar BA, Lehner CF (1996). Developmental control of cell cycle regulators: a fly's perspective. [Review]. Science, 274(5293), 1646-52. (Read full article)
  19. Edgar B (1995). Diversification of cell cycle controls in developing embryos. [Review]. Curr Opin Cell Biol, 7(6), 815-24. (Read full article)
  20. Edgar BA (1994). Cell cycle. Cell-cycle control in a developmental context. [Review]. Curr Biol, 4(6), 522-4. (Read full article)
  21. OFarrell PH, Edgar BA, Lakich D, Lehner CF (1989). Directing cell division during development. [Review]. Science, 246(4930), 635-40. (Read full article)

Book Chapter

  1. Zhang P, Edgar BA (2022). Insect Gut Regeneration. In Cold Spring Harb Perspect Biol (14). United States. (Read full article)
  2. Zielke N, Edgar BA, DePamphilis ML (2013). Endoreplication. In Cold Spring Harb Perspect Biol (5, pp. a012948). United States. (Read full article)
  3. Wang T, Edgar BA (2010). TOR signaling and cell death. In F. Tamanoi, M.N. Hall (Eds.), The Enzymes (28, pp. 217-44).
  4. de la Cruz AF, Edgar BA (2008). Flow cytometric analysis of Drosophila cells. In Methods Mol Biol (420, pp. 373-89). United States. (Read full article)
  5. Edgar B, Nijhout HF (2004). Growth and Cell Cycle Control in Drosophila. In M. Hall, M. Raff, and G. Thomas (Eds.), Cell Growth: Control of Cell Size (pp. 23-83). Cold Spring Harbor Laboratory Press.
  6. Edgar BA, Britton J, de la Cruz AF, Johnston LA, Lehman D, Martin-Castellanos C, Prober D (2001). Pattern- and growth-linked cell cycles in Drosophila development. In Novartis Found Symp (237, pp. 3-12; discussion 12-8, 36-42). England. (Read full article)
  7. Schubiger G, Edgar B (1994). Using inhibitors to study embryogenesis. In Methods Cell Biol (44, pp. 697-713). United States. (Read full article)
  8. Foe VE, Odell GM, Edgar BA (1993). Mitosis and morphogenesis in the Drosophila embryo: Point and counterpoint. In M. Bate, A. Martinez Arias (Eds.), The Development of Drosophila melanogaster (pp. 149-300). Cold Spring Harbor Laboratory Press.

Commentary

  1. Ma Y, Edgar BA (2021). CDK4: Linking cell size to cell cycle control. Dev Cell, 56(12), 1695-1696. (Read full article)
  2. Zhang P, Edgar BA (2020). Lipoic acid and autophagy: new insights into stem cell aging. EMBO Rep, 21(8), e51175. (Read full article)
  3. Zhang P, Holowatyj AN, Ulrich CM, Edgar BA (2019). Tumor suppressive autophagy in intestinal stem cells controls gut homeostasis. Autophagy, 15(9), 1668-1670. (Read full article)
  4. Edgar BA, Grewal SS (2017). Longer life through an odd Pol enzyme. Nature, 552(7684), 182-183. (Read full article)
  5. Zielke N, Edgar BA (2015). FUCCI sensors: powerful new tools for analysis of cell proliferation. Wiley Interdiscip Rev Dev Biol, 4(5), 469-87. (Read full article)
  6. Knop M, Edgar BA (2014). Tracking protein turnover and degradation by microscopy: photo-switchable versus time-encoded fluorescent proteins. Open Biol, 4, 140002. (Read full article)
  7. Patel PH, Edgar BA (2014). Tissue design: how Drosophila tumors remodel their neighborhood. Semin Cell Dev Biol, 28, 86-95. (Read full article)
  8. Patel PH, Maldera JA, Edgar BA (2013). Stimulating cROSstalk between commensal bacteria and intestinal stem cells. EMBO J, 32(23), 3009-10. (Read full article)
  9. Edgar BA (2012). Intestinal stem cells: no longer immortal but ever so clever.... EMBO J, 31(11), 2441-3. (Read full article)
  10. Edgar BA, Kim KJ (2009). Cell biology. Sizing up the cell. Science, 325(5937), 158-9. (Read full article)
  11. Bandura JL, Edgar BA (2008). Yorkie and Scalloped: partners in growth activation. Dev Cell, 14(3), 315-6. (Read full article)

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