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1: Venkitaraman AR. Cancer: Let sleeping DNA lie. Nature. 2011 Sep 7;477(7363):169-70. doi: 10.1038/477169a. PubMed PMID: 21901006. 2: Venkitaraman AR.

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Presentation on theme: "1: Venkitaraman AR. Cancer: Let sleeping DNA lie. Nature. 2011 Sep 7;477(7363):169-70. doi: 10.1038/477169a. PubMed PMID: 21901006. 2: Venkitaraman AR."— Presentation transcript:

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2 1: Venkitaraman AR. Cancer: Let sleeping DNA lie. Nature. 2011 Sep 7;477(7363):169-70. doi: 10.1038/477169a. PubMed PMID: 21901006. 2: Venkitaraman AR. Does metabolite deficiency mark oncogenic cell cycles? Cell. 2011 Apr 29;145(3):337-8. PubMed PMID: 21529708. 3: Jeyasekharan AD, Ayoub N, Mahen R, Ries J, Esposito A, Rajendra E, Hattori H, Kulkarni RP, Venkitaraman AR. DNA damage regulates the mobility of Brca2 within the nucleoplasm of living cells. Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21937-42. 4: Hattori H, Skoulidis F, Russell P, Venkitaraman AR. Context dependence of checkpoint kinase 1 as a therapeutic target for pancreatic cancers deficient in the BRCA2 tumor suppressor. Mol Cancer Ther. 2011 Apr;10(4):670-8. 5: Skoulidis F, Cassidy LD, Pisupati V, Jonasson JG, Bjarnason H, Eyfjord JE, Karreth FA, Lim M, Barber LM, Clatworthy SA, Davies SE, Olive KP, Tuveson DA, Venkitaraman AR. Germline Brca2 heterozygosity promotes Kras(G12D) –driven carcinogenesis in a murine model of familial pancreatic cancer. Cancer Cell. 2010 Nov 16;18(5):499-509.. 6: Sato K, Ohta T, Venkitaraman AR. A mitotic role for the DNA damage-responsive CHK2 kinase. Nat Cell Biol. 2010 May;12(5):424-5. PubMed PMID: 20442702. 7: Garnett MJ, Mansfeld J, Godwin C, Matsusaka T, Wu J, Russell P, Pines J, Venkitaraman AR. UBE2S elongates ubiquitin chains on APC/C substrates to promote mitotic exit. Nat Cell Biol. 2009 Nov;11(11):1363-9. 8: Ayoub N, Jeyasekharan AD, Venkitaraman AR. Mobilization and recruitment of HP1: a bimodal response to DNA breakage. Cell Cycle. 2009 Sep 15;8(18):2945-50. Review. PubMed PMID: 19657222.

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6 Selected References Sun D, Lee YS, Malhotra A, Kim HK, Matecic M, Evans C, Jensen RV, Moskaluk CA,Dutta A. (2011) "miR-99 Family of MicroRNAs Suppresses the Expression of Prostate-Specific Antigen and Prostate Cancer Cell Proliferation." Cancer Res. Feb [Epub ahead of print] [PubMed] [PubMed] Lin JJ, Milhollen MA, Smith PG, Narayanan U, Dutta A. (2010) "NEDD8-targeting drug MLN4924 elicits DNA rereplication by stabilizing Cdt1 in S phase, triggering checkpoint activation, apoptosis, and senescence in cancer cells." Cancer Res. Dec 70(24):10310-20. [PubMed] [PubMed] Dey BK, Gagan J, Dutta A. (2011) "miR-206 and -486 induce myoblast differentiation by downregulating Pax7." Mol Cell Biol. 31:203-14. Epub 2010 Nov 1. [PubMed][PubMed] Abbas T, Shibata E, Park J, Jha S, Karnani N, Dutta A. (2010) "CRL4(Cdt2) regulates cell proliferation and histone gene expression by targeting PR-Set7/Set8 for degradation." Mol Cell. Oct 40:9-21. [PubMed][PubMed] Shibata Y, Malhotra A, Dutta A. (2010) "Detection of DNA fusion junctions for BCR-ABL translocations by Anchored ChromPET." Genome Med. Sep 2:70. [PubMed][PubMed] Jha S, Vande Pol S, Banerjee NS, Dutta AB, Chow LT, Dutta A. (2010) "Destabilization of TIP60 by human papillomavirus E6 results in attenuation of TIP60-dependent transcriptional regulation and apoptotic pathway." Mol Cell. Jun 38:700-11. [PubMed][PubMed] Sarkar S, Dey BK, Dutta A. (2010) "MiR-322/424 and -503 are induced during muscle differentiation and promote cell cycle quiescence and differentiation by down-regulation of Cdc25A." Mol Biol Cell. 21(13):2138-49. Epub 2010 May 12. [PubMed][PubMed] Terai K, Abbas T, Jazaeri AA, Dutta A. (2010) "CRL4(Cdt2) E3 ubiquitin ligase monoubiquitinates PCNA to promote translesion DNA synthesis." Mol Cell. Jan 37:143-9. [PubMed] [PubMed]

7 http://genome.bioch.virginia.edu

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12 Surani MA and Hajkova P. (2010) Epigenetic reprogramming of mouse germ cells towards totipotency. Cold Spring Harbor Symposium on Nuclear Organisation and Function,Volume LXXV Hajkova P, Jeffries SJ, Lee C, Miller N, Jackson SP, Surani MA. (2010) Genome- wide reprogramming in the mouse germ line entails the base excision repair pathway Science 329,78-82 Tang F,Barbacioru C,Bao S,Lee C,Nordman E,Wang X, Lao K, Surani MA. (2010) Tracing the derivation of embryonic stem cells from the inner cell mass by single cell RNA-Seq analysis Cell Stem Cell 6, 468-478 Bao S,Tang F, Li X, Hayashi K, Gillich A, Lao K, Surani MA. (2009) Epigenetic reversion of postimplantation epiblast to pluripotent embryonic stem cells Nature 461, 1292-1295 Hajkova P, Ancelin K, Waldmann T, Lacoste N, Lange UC, Cesari F, Lee C, Almouzni G, Schneider R, Surani MA. (2008) Chromatin dynamics during epigenetic reprogramming in the mouse germ line Nature 452, 877-881

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14 References: Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K. Induced pluripotent stem cells generated without viral integration. Science 2008 Nov 7;322(5903):945-9. Eminli S, Foudi A, Stadtfeld M, Maherali N, Ahfeldt T, Mostoslavsky G, Hock H, Hochedlinger K. Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cells. Nat Genet. 2009 Sep;41(9):968-76. Epub 2009 Aug 9. Utikal J, Polo JM, Stadtfeld M, Maherali N, Kulalert W, Walsh RM, Khalil A, Rheinwald JG, Hochedlinger K. Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature. 2009 Aug 27;460(7259):1145-8. Stadtfeld M, Apostolou E, Akutsu H, Fukuda A, Follett P, Natesan S, Kono T, Shioda T, Hochedlinger K. Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells. Nature. 2010 Apr 25. [Epub ahead of print] Induced pluripotency: history, mechanisms, and applications. Stadtfeld M, Hochedlinger K. Genes Dev. 2010 Oct 15;24(20):2239-63. Review. Chromatin connections to pluripotency and cellular reprogramming. Orkin SH, Hochedlinger K. Cell. 2011 Jun 10;145(6):835-50

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16 1: Sykes SM, Lane SW, Bullinger L, Kalaitzidis D, Yusuf R, Saez B, Ferraro F, Mercier F, Singh H, Brumme KM, Acharya SS, Schöll C, Tothova Z, Attar EC,Fröhling S, Depinho RA, Armstrong SA, Gilliland DG, Scadden DT. AKT/FOXO Signaling Enforces Reversible Differentiation Blockade in Myeloid Leukemias.Cell. 2011 Sep 2;146(5):697-708. 2: Lane SW, Wang YJ, Lo Celso C, Ragu C, Bullinger L, Sykes SM, Ferraro F, Shterental S, Lin CP, Gilliland DG, Scadden DT, Armstrong SA, Williams DA. Differential niche and Wnt requirements during acute myeloid leukemia progression. Blood. 2011 Sep 8;118(10):2849-56. 3: Fujisaki J, Wu J, Carlson AL, Silberstein L, Putheti P, Larocca R, Gao W, Saito TI, Lo Celso C, Tsuyuzaki H, Sato T, Côté D, Sykes M, Strom TB, Scadden DT, Lin CP. In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche. Nature. 2011 Jun 8;474(7350):216-9. 4: Cornejo MG, Mabialah V, Sykes SM, Khandan T, Lo Celso C, Lopez CK, Rivera-Muñoz P, Rameau P, Tothova Z, Aster JC, DePinho RA, Scadden DT, Gilliland DG, Mercher T. Crosstalk between NOTCH and AKT signaling during murine megakaryocyte lineage specification. Blood. 2011 Aug 4;118(5):1264-73. 5: Sanchez-Aguilera A, Lee YJ, Lo Celso C, Ferraro F, Brumme K, Mondal S, Kim C, Dorrance A, Luo HR, Scadden DT, Williams DA. Guanine nucleotide exchange factor Vav1 regulates perivascular homing and bone marrow retention of hematopoietic stem and progenitor cells. Proc Natl Acad Sci U S A. 2011 Jun 7;108(23):9607-12. 6: Vallet S, Pozzi S, Patel K, Vaghela N, Fulciniti MT, Veiby P, Hideshima T, Santo L, Cirstea D, Scadden DT, Anderson KC, Raje N. A novel role for CCL3 (MIP-1α) in myeloma-induced bone disease via osteocalcin downregulation and inhibition of osteoblast function. Leukemia. 2011 Jul;25(7):1174-81. 7: Steinbicker AU, Sachidanandan C, Vonner AJ, Yusuf RZ, Deng DY, Lai CS,Rauwerdink KM, Winn JC, Saez B, Cook CM, Szekely BA, Roy CN, Seehra JS, Cuny GD, Scadden DT, Peterson RT, Bloch KD, Yu PB. Inhibition of bone morphogenetic protein signaling attenuates anemia associated with inflammation. Blood. 2011 May 5;117(18):4915-23. 8: Vunjak-Novakovic G, Scadden DT. Biomimetic platforms for human stem cell research. Cell Stem Cell. 2011 Mar 4;8(3):252-61. 9: Lo Celso C, Lin CP, Scadden DT. In vivo imaging of transplanted hematopoietic stem and progenitor cells in mouse calvarium bone marrow. Nat Protoc. 2011 Jan;6(1):1-14. 10: Lane AA, Scadden DT. Stem cells and DNA damage: persist or perish? Cell. 2010 Aug 6;142(3):360-2.

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18 1: Park D, Han CZ, Elliott MR, Kinchen JM, Trampont PC, Das S, Collins S, Lysiak JJ, Hoehn KL, Ravichandran KS. Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2 protein. Nature. 2011 Aug 21;477(7363):220-4. 2: Armstrong A, Ravichandran KS. Phosphatidylserine receptors: what is the new RAGE? EMBO Rep. 2011 Apr 1;12(4):287-8. Epub 2011 Mar 11. 3: Das S, Owen KA, Ly KT, Park D, Black SG, Wilson JM, Sifri CD, Ravichandran KS, Ernst PB, Casanova JE. Brain angiogenesis inhibitor 1 (BAI1) is a pattern recognition receptor that mediates macrophage binding and engulfment of Gram-negative bacteria. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2136-41. 4: Elliott MR, Ravichandran KS. ELMO1 signaling in apoptotic germ cell clearance and spermatogenesis. Ann N Y Acad Sci. 2010 Oct;1209:30-6. 5: Chekeni FB, Elliott MR, Sandilos JK, Walk SF, Kinchen JM, Lazarowski ER, Armstrong AJ, Penuela S, Laird DW, Salvesen GS, Isakson BE, Bayliss DA, Ravichandran KS. Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis. Nature. 2010 Oct 14;467(7317):863-7. 6: Elliott MR, Zheng S, Park D, Woodson RI, Reardon MA, Juncadella IJ, Kinchen JM, Zhang J, Lysiak JJ, Ravichandran KS. Unexpected requirement for ELMO1 in clearance of apoptotic germ cells in vivo. Nature. 2010 Sep 16;467(7313):333-7. 7: Kinchen JM, Ravichandran KS. Identification of two evolutionarily conserved genes regulating processing of engulfed apoptotic cells. Nature. 2010 Apr 1;464(7289):778-82. Epub 2010 Mar 21. 9: Giles AJ, Bender TP, Ravichandran KS. The adaptor protein Shc plays a key role during early B cell development. J Immunol. 2009 Nov 1;183(9):5468-76. 10: Elliott MR, Chekeni FB, Trampont PC, Lazarowski ER, Kadl A, Walk SF, Park D, Woodson RI, Ostankovich M, Sharma P, Lysiak JJ, Harden TK, Leitinger N, Ravichandran KS. Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature. 2009 Sep 10;461(7261):282-6.

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20 Gastroenterology and Hepatology 1.Yao Z, Mishra L. Cancer stem cells and hepatocellular carcinoma. Cancer Biol Ther 8(18):1691- 8, 9/2009. PMID: 19901516.Yao Z, Mishra L 2.Lin L, Amin R, Gallicano GI, Glasgow E, Jogunoori W, Jessup JM, Zasloff M, Marshall JL, Shetty K, Johnson L, Mishra L, He AR. The STAT3 inhibitor NSC 74859 is effective in hepatocellular cancers with disrupted TGF-beta signaling. Oncogene 28(7):961-72, 2/2009. e-Pub 1/2009. PMCID: PMC2703464.Lin L, Amin R, Gallicano GI, Glasgow E, Jogunoori W, Jessup JM, Zasloff M, Marshall JL, Shetty K, Johnson L, Mishra L, He AR 3.Mishra L, Banker T, Murray J, Byers S, Thenappan A, He AR, Shetty K, Johnson L, Reddy EP. Liver stem cells and hepatocellular carcinoma. Hepatology 49(1):318-29, 1/2009. PMCID: PMC2726720.Mishra L, Banker T, Murray J, Byers S, Thenappan A, He AR, Shetty K, Johnson L, Reddy EP 4.Mishra L. The 21st century hepatologist and a systems biology based approach to liver diseases. Hepatology 48(6):1731-3, 12/2008. PMCID: PMC2712824.Mishra L 5.Baek HJ, Lim SC, Kitisin K, Jogunoori W, Tang Y, Marshall MB, Mishra B, Kim TH, Cho KH, Kim SS, Mishra L. Hepatocellular cancer arises from loss of transforming growth factor beta signaling adaptor protein embryonic liver fodrin through abnormal angiogenesis. Hepatology 48(4):1128-37, 10/2008. PMCID: PMC2747753.Baek HJ, Lim SC, Kitisin K, Jogunoori W, Tang Y, Marshall MB, Mishra B, Kim TH, Cho KH, Kim SS, Mishra L 6.Fishbein T, Novitskiy G, Mishra L, Matsumoto C, Kaufman S, Goyal S, Shetty K, Johnson L, Lu A, Wang A, Hu F, Kallakury B, Lough D, Zasloff M. NOD2-expressing bone marrow-derived cells appear to regulate epithelial innate immunity of the transplanted human small intestine. Gut 57(3):323-30, 3/2008. e-Pub 10/2007. PMID: 17965060.Fishbein T, Novitskiy G, Mishra L, Matsumoto C, Kaufman S, Goyal S, Shetty K, Johnson L, Lu A, Wang A, Hu F, Kallakury B, Lough D, Zasloff M 7.Glasgow E, Mishra L. Transforming growth factor-beta signaling and ubiquitinators in cancer. Endocr Relat Cancer 15(1):59-72, 3/2008. PMID: 18310276.Glasgow E, Mishra L

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22 Tobin, D.M., Vary Jr, J.P. Ray, G.S. Walsh, S.J. Dunstan, N.D. Bang, D.A. Hagge, S. Khadge, M-C. King, T.R. Hawn, C.B. Moens, L. Ramakrishnan. The lta4h Locus Modulates Susceptibility to Mycobacterial Infection in Zebrafish and Humans. Cell 140:717-730. H. E. Volkman, T. C. Pozos, J. Zheng, J.M. Davis, F. Chu, J. F. Rawls, L. Ramakrishnan (2010). Tuberculous granuloma induction via interactions of a bacterial secreted protein with host epithelium. Science, 327:466-469. J.M. Davis and L. Ramakrishnan. 2009. The role of the granuloma in the expansion and dissemination of early tuberculous infection. Cell 136:37-49. H. Clay, HE Volkman and L. Ramakrishnan. 2008. TNF signaling mediates resistance to mycobacteria by inhibiting bacterial growth and macrophage death but is not required for tuberculous granuloma formation. Immunity 29:283-294. H. Clay, J.M. Davis, D. Beery, A. Huttenlocher, S. E. Lyons and L. Ramakrishnan. 2007. Dichotomous role of the macrophage in early Mycobacterium marinum infection of the zebrafish. Cell Host and Microbe 2:29-39.

23 Scadden: Haematopoiesis and Niche Konrad: iPS cells Venki: Ribosomes structure and function Shiv Pillai: Lymphocyte development Ashok: Cancer Biology Anindya: DNA replication and miRNAs Tim Hunt: Cell cycle regulation Lopa: Gastroenterology and hepatology Lalita: Infection and Immunology Kodi: Apoptosis and lymphocyte development Azim: Germ cells, reproduction and epigenetics

24 Form groups

25 Who is the senior most in each group?

26 Present three latest articles of the selected scientist. –Three speakers will present three articles from each group. –The others in the group should have read the articles and help the presenters with the presentation –Answer the questions from other groups


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