DF/HCC Program Affiliation

Cancer Cell Biology
Cancer Genetics

Research Abstract

I am interested in a number of areas relevant to cancer biology. I have had extensive experience in unraveling the signaling pathways involved in sensing and responding to DNA damage. This has involved both yeast and mammalian systems. We have performed work on the yeast Mec1, Mrc1, Rad53, Chk1, Dun1, Crt1, RNR1, RNR2, RNR3 and RNR4 genes as well as a number of cell cycle regulators including Cdc5 and the mitotic exit network genes Bub1, Bfa1 and Amn1. In mammals we have worked on the ATM, ATR,ATRIP, RPA, Rad17, Claspin, Chk1, Chk2,Cdc25 and p53 genes. I am continuing to explore new avenues in DNA damage signaling. In addiiton to our interests in DNA damage and cell cycle regulation in general, I have worked extensively in the past on Cdk regulation including Cdk2, cyclin A, cyclin F, and the p21 family of Cdk inhibitors, CKIs, including the Beckwith-Weidemann gene, p57. More recently our studies of cyclin and CKI metabolism led to the discovery of F-box proteins and the SCF pathway of regulated protein stability. Our more recent studies have focussed on development of genetic methods to over-express and knock-out mammalian genes using siRNA to perform genetic screens in mammalian cells.

Publications

• Stegmeier F, Rape M, Draviam VM, Nalepa G, Sowa ME, Ang XL, McDonald ER, Li MZ, Hannon GJ, Sorger PK, Kirschner MW, Harper JW, Elledge SJ.Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities.Nature 2007 Apr 19;44
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• Draviam VM, Stegmeier F, Nalepa G, Sowa ME, Chen J, Liang A, Hannon GJ, Sorger PK, Harper JW, Elledge SJ.A functional genomic screen identifies a role for TAO1 kinase in spindle-checkpoint signalling.Nat Cell Biol 2007 May;9(5):556-64.
  17417629
• Smogorzewska A, Matsuoka S, Vinciguerra P, McDonald ER, Hurov KE, Luo J, Ballif BA, Gygi SP, Hofmann K, D'Andrea AD, Elledge SJ.Identification of the FANCI Protein, a Monoubiquitinated FANCD2 Paralog Required for DNA Repair.Cell 2007 Apr 20;129(2):289-301
  17412408
• Zaugg K, Su YW, Reilly PT, Moolani Y, Cheung CC, Hakem R, Hirao A, Elledge SJ, Mak TW.Cross-talk between Chk1 and Chk2 in double-mutant thymocytes.Proc Natl Acad Sci U S A 2007 Mar 6;104(10):3805-10.
  17360434
• Li MZ, Elledge SJ.Harnessing homologous recombination in vitro to generate recombinant DNA via SLIC.Nat Methods 2007 Mar;4(3):251-6.
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• Chou DM, Elledge SJ.Tipin and Timeless form a mutually protective complex required for genotoxic stress resistance and checkpoint function.Proc Natl Acad Sci U S A 2006 Nov 28;103(48):18143-7.
  17116885
• Chang K, Elledge SJ, Hannon GJ.Lessons from Nature: microRNA-based shRNA libraries.Nat Methods 2006 Sep;3(9):707-14.
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• Zhang D, Zaugg K, Mak TW, Elledge SJ.A role for the deubiquitinating enzyme USP28 in control of the DNA-damage response.Cell 2006 Aug 11;126(3):529-42.
  16901786
• Wang X, Zou L, Lu T, Bao S, Hurov KE, Hittelman WN, Elledge SJ, Li L.Rad17 phosphorylation is required for claspin recruitment and chk1 activation in response to replication stress.Mol Cell 2006 Aug 4;23(3):331-41.
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• Westbrook TF, Stegmeier F, Elledge SJ.Dissecting cancer pathways and vulnerabilities with RNAi.Cold Spring Harb Symp Quant Biol 2005;70:435-44.
  16869781
• Paddison PJ, Silva JM, Conklin DS, Schlabach M, Li M, Aruleba S, Balija V, O'Shaughnessy A, Gnoj L, Scobie K, Chang K, Westbrook T, Cleary M, Sachidanandam R, McCombie WR, Elledge SJ, Hannon GJ.A resource for large-scale RNA-interference-based screens in
  15042091
• Lin SY, Elledge SJ.Multiple tumor suppressor pathways negatively regulate telomerase.Cell 2003 Jun 27;113(7):881-9.
  12837246
• Zou L, Elledge SJ.Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes.Science 2003 Jun 6;300(5625):1542-8.
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• Alcasabas AA, Osborn AJ, Bachant J, Hu F, Werler PJ, Bousset K, Furuya K, Diffley JF, Carr AM, Elledge SJ.Mrc1 transduces signals of DNA replication stress to activate Rad53.Nat Cell Biol 2001 Nov;3(11):958-65.
  11715016
• Zhang P, Liégeois NJ, Wong C, Finegold M, Hou H, Thompson JC, Silverman A, Harper JW, DePinho RA, Elledge SJ.Altered cell differentiation and proliferation in mice lacking p57KIP2 indicates a role in Beckwith-Wiedemann syndrome.Nature 1997 May 8;387(6629)
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