Professor John Sedivy joined the Brown Faculty in 1996 and is a member of the Department of Molecular Biology, Cell Biology and Biochemistry. He obtained his PhD from Harvard in 1985, and subsequently trained with the Nobel Laureate Philip Sharp at the MIT Center for Cancer Research. He started his independent research career at Yale University in 1988.
John Sedivy's research on cell cycle regulation and signal transduction, focusing initially on the Myc oncogene and subsequently on replicative senescence (cellular aging), has been continuously funded by the National Institutes of Health since 1989. In 2003 he became interested in genomics, and his work on Myc-regulated gene networks led to an involvement in bioinformatics and systems biology. In 2004 his lab started work on single-cell assays of cellular senescence by developing a robust biomarker of telomere-initiated senescence. Using this assay they delineated the signaling pathways between dysfunctional telomeres and the cell cycle, and in 2006 published the first comprehensive in vivo quantification of cellular senescence in aging primates. In 2006 they also discovered that c-Myc contributes to the regulation of chromatin states though the Polycomb pathway, initiating their entry into epigenetics. This led to the development of single-cell assays showing age-associated in vivo expansion of heterochromatin, and current studies of genome-wide chromatin changes in cellular senescence as well as organismal aging.
In addition to writing the first comprehensive book on gene targeting in 1992, John Sedivy has published over 140 original articles. He has served on numerous study sections and advisory committees at the National Institutes of Health, the American Cancer Society, and the US Army Breast Cancer Initiative. He has consulted extensively on the genetic manipulation of mammalian cells to the biotech industry, including Biogen, Eli Lilly & Co., Abbott Laboratories, and Millenium Pharmaceuticals. He maintains an active role in the field of aging, as a founding member (and current chair) of the CMAD study section at the National Institutes of Health, co-Editor-in-Chief of the journal Aging Cell, and chair of the 2015 Gordon Research Conference on the Biology of Aging. He has fulfilled major administrative leadership roles at Brown University, including chairing the Department of Molecular Biology, Cell Biology and Biochemistry, and founding an academic center for Genomics and Proteomics.
| Waaijer, Mariëtte E.C., Gunn, David A., van Heemst, Diana, Slagboom, P. Eline, Sedivy, John M., Dirks, Roeland W., Tanke, Hans J., Westendorp, Rudi G.J., Maier, Andrea B. "Do senescence markers correlate in vitro and in situ within individual human donors?." Aging, 2018. |
| Ito, Takahiro, Teo, Yee Voan, Evans, Shane A., Neretti, Nicola, Sedivy, John M. "Regulation of Cellular Senescence by Polycomb Chromatin Modifiers through Distinct DNA Damage- and Histone Methylation-Dependent Pathways." Cell Reports, vol. 22, no. 13, 2018, pp. 3480-3492. |
| "DNA damage markers in dermal fibroblasts in vitro reflect chronological donor age." Aging, vol. 8, no. 1, 2016, pp. 147-157. |
| Tatar M, Sedivy JM. "Mitochondria: Masters of Epigenetics." Cell, vol. 165, no. 5, 2016, pp. 1052-1054. |
| Tatar M, Sedivy JM. "Mitochondria: Masters of Epigenetics." Cell, vol. 165, no. 5, 2016, pp. 1052-4. |
| Gravina, Silvia, Sedivy, John M., Vijg, Jan. "The dark side of circulating nucleic acids." Aging Cell, vol. 15, no. 3, 2016, pp. 398-399. |
| Giampieri, Enrico, De Cecco, Marco, Remondini, Daniel, Sedivy, John, Castellani, Gastone. "Active Degradation Explains the Distribution of Nuclear Proteins during Cellular Senescence." PLoS ONE, vol. 10, no. 6, 2015, pp. e0118442. |
| Longo VD, Antebi A, Bartke A, Barzilai N, Brown-Borg HM, Caruso C, Curiel TJ, de Cabo R, Franceschi C, Gems D, Ingram DK, Johnson TE, Kennedy BK, Kenyon C, Klein S, Kopchick JJ, Lepperdinger G, Madeo F, Mirisola MG, Mitchell JR, Passarino G, Rudolph KL, Sedivy JM, Shadel GS, Sinclair DA, Spindler SR, Suh Y, Vijg J, Vinciguerra M, Fontana L. "Interventions to Slow Aging in Humans: Are We Ready?." Aging Cell, 2015. |
| Hofmann JW, Zhao X, De Cecco M, Peterson AL, Pagliaroli L, Manivannan J, Hubbard GB, Ikeno Y, Zhang Y, Feng B, Li X, Serre T, Qi W, Van Remmen H, Miller RA, Bath KG, de Cabo R, Xu H, Neretti N, Sedivy JM. "Reduced expression of MYC increases longevity and enhances healthspan." Cell, vol. 160, no. 3, 2015, pp. 477-88. |
| Nelson DM, McBryan T, Jeyapalan JC, Sedivy JM, Adams PD. "A comparison of oncogene-induced senescence and replicative senescence: implications for tumor suppression and aging." Age (Dordrecht, Netherlands), vol. 36, no. 3, 2014, pp. 9637. |
| Gorbunova, V., Boeke, J. D., Helfand, S. L., Sedivy, J. M. "Sleeping dogs of the genome." Science, vol. 346, no. 6214, 2014, pp. 1187-1188. |
| Hofmann JW, McBryan T, Adams PD, Sedivy JM. "The effects of aging on the expression of Wnt pathway genes in mouse tissues." Age (Dordrecht, Netherlands), vol. 36, no. 3, 2014, pp. 9618. |
| Criscione SW, Zhang Y, Thompson W, Sedivy JM, Neretti N. "Transcriptional landscape of repetitive elements in normal and cancer human cells." BMC genomics, vol. 15, 2014, pp. 583. |
| Sedivy JM, Kreiling JA, Neretti N, De Cecco M, Criscione SW, Hofmann JW, Zhao X, Ito T, Peterson AL. "Death by transposition - the enemy within?." BioEssays : news and reviews in molecular, cellular and developmental biology, vol. 35, no. 12, 2013, pp. 1035-43. |
| De Cecco M, Criscione SW, Peckham EJ, Hillenmeyer S, Hamm EA, Manivannan J, Peterson AL, Kreiling JA, Neretti N, Sedivy JM. "Genomes of replicatively senescent cells undergo global epigenetic changes leading to gene silencing and activation of transposable elements." Aging Cell, vol. 12, no. 2, 2013, pp. 247-56. |
| Jeyapalan JC, Sedivy JM. "How to measure RNA expression in rare senescent cells expressing any specific protein such as p16Ink4a." Aging, vol. 5, no. 2, 2013, pp. 120-9. |
| Baker DJ, Sedivy JM. "Probing the depths of cellular senescence." The Journal of cell biology, vol. 202, no. 1, 2013, pp. 11-3. |
| De Cecco M, Criscione SW, Peterson AL, Neretti N, Sedivy JM, Kreiling JA. "Transposable elements become active and mobile in the genomes of aging mammalian somatic tissues." Aging, vol. 5, no. 12, 2013, pp. 867-83. |
| Sedivy JM, van Deursen JM. "Why do we grow old: is it because our cells just wear out, we run out of cells (or both), and what can we do about it?." Longevity & healthspan, vol. 2, no. 1, 2013, pp. 7. |
| Sanders JA, Schorl C, Patel A, Sedivy JM, Gruppuso PA. "Postnatal liver growth and regeneration are independent of c-myc in a mouse model of conditional hepatic c-myc deletion." BMC physiology, vol. 12, 2012, pp. 1. |
| Moen EL, Wen S, Anwar T, Cross-Knorr S, Brilliant K, Birnbaum F, Rahaman S, Sedivy JM, Moss SF, Chatterjee D. "Regulation of RKIP function by Helicobacter pylori in gastric cancer." PLoS ONE, vol. 7, no. 5, 2012, pp. e37819. |
| Zwolinska AK, Heagle Whiting A, Beekman C, Sedivy JM, Marine JC. "Suppression of Myc oncogenic activity by nucleostemin haploinsufficiency." Oncogene, vol. 31, no. 28, 2012, pp. 3311-21. |
| Waaijer ME, Parish WE, Strongitharm BH, van Heemst D, Slagboom PE, de Craen AJ, Sedivy JM, Westendorp RG, Gunn DA, Maier AB. "The number of p16INK4a positive cells in human skin reflects biological age." Aging Cell, vol. 11, no. 4, 2012, pp. 722-5. |
| Kreiling JA, Tamamori-Adachi M, Sexton AN, Jeyapalan JC, Munoz-Najar U, Peterson AL, Manivannan J, Rogers ES, Pchelintsev NA, Adams PD, Sedivy JM. "Age-associated increase in heterochromatic marks in murine and primate tissues." Aging Cell, vol. 10, no. 2, 2011, pp. 292-304. |
| Muñoz-Najar U, Sedivy JM. "Epigenetic control of aging." Antioxidants & redox signaling, vol. 14, no. 2, 2011, pp. 241-59. |
| Yap CS, Peterson AL, Castellani G, Sedivy JM, Neretti N. "Kinetic profiling of the c-Myc transcriptome and bioinformatic analysis of repressed gene promoters." Cell Cycle, vol. 10, no. 13, 2011, pp. 2184-96. |
| De Cecco M, Jeyapalan J, Zhao X, Tamamori-Adachi M, Sedivy JM. "Nuclear protein accumulation in cellular senescence and organismal aging revealed with a novel single-cell resolution fluorescence microscopy assay." Aging, vol. 3, no. 10, 2011, pp. 955-67. |
| Sedivy JM. "Phosphatidylenthanolamine Binding Protein aka Raf Kinase Inhibitor Protein: A Brief History of Its Discovery and the Remarkable Diversity of Biological Functions." Forum on immunopathological diseases and therapeutics, vol. 2, no. 1, 2011, pp. 1-12. |
| Alves H, Munoz-Najar U, De Wit J, Renard AJ, Hoeijmakers JH, Sedivy JM, Van Blitterswijk C, De Boer J. "A link between the accumulation of DNA damage and loss of multi-potency of human mesenchymal stromal cells." Journal of cellular and molecular medicine, vol. 14, no. 12, 2010, pp. 2729-38. |
| Agrawal P, Yu K, Salomon AR, Sedivy JM. "Proteomic profiling of Myc-associated proteins." Cell Cycle, vol. 9, no. 24, 2010, pp. 4908-21. |
| Jimenez RH, Lee JS, Francesconi M, Castellani G, Neretti N, Sanders JA, Sedivy J, Gruppuso PA. "Regulation of gene expression in hepatic cells by the mammalian Target of Rapamycin (mTOR)." PLoS ONE, vol. 5, no. 2, 2010, pp. e9084. |
| Paul E, Kielbasinski M, Sedivy JM, Murga-Zamalloa C, Khanna H, Klysik JE. "Widespread expression of the Supv3L1 mitochondrial RNA helicase in the mouse." Transgenic research, vol. 19, no. 4, 2010, pp. 691-701. |
| Paul E, Cronan R, Weston PJ, Boekelheide K, Sedivy JM, Lee SY, Wiest DL, Resnick MB, Klysik JE. "Disruption of Supv3L1 damages the skin and causes sarcopenia, loss of fat, and death." Mammalian genome : official journal of the International Mammalian Genome Society, vol. 20, no. 2, 2009, pp. 92-108. |
| Campisi J, Sedivy J. "How does proliferative homeostasis change with age? What causes it and how does it contribute to aging?." The Journals of Gerontology: Series A, vol. 64, no. 2, 2009, pp. 164-6. |
| Sedivy JM. "How to learn new and interesting things from model systems based on "exotic" biological species." Proceedings of the National Academy of Sciences, vol. 106, no. 46, 2009, pp. 19207-8. |
| Sedivy JM, Banumathy G, Adams PD. "Aging by epigenetics--a consequence of chromatin damage?." Experimental Cell Research, vol. 314, no. 9, 2008, pp. 1909-17. |
| Jeyapalan JC, Sedivy JM. "Cellular senescence and organismal aging." Mechanisms of Ageing and Development, vol. 129, no. 7-8, 2008, pp. 467-74. |
| Liu YC, Li F, Handler J, Huang CR, Xiang Y, Neretti N, Sedivy JM, Zeller KI, Dang CV. "Global regulation of nucleotide biosynthetic genes by c-Myc." PLoS ONE, vol. 3, no. 7, 2008, pp. e2722. |
| Ferrandiz, N., Acosta, J.C., Bretones, G., Torrano, V., Blanco, R., Richard, C., O'Conell, B., Sedivy, J., Delgado, M.D., Leon, J. "MYC inhibition of p27-induced erythroid differentiation is mediated by the repression of erythroid master genes and uncoupled from its cell cycle promoting activity." European Journal of Cancer Supplements, vol. 6, no. 9, 2008, pp. 79-80. |
| Acosta JC, Ferrándiz N, Bretones G, Torrano V, Blanco R, Richard C, O'Connell B, Sedivy J, Delgado MD, León J. "Myc inhibits p27-induced erythroid differentiation of leukemia cells by repressing erythroid master genes without reversing p27-mediated cell cycle arrest." Molecular and Cellular Biology, vol. 28, no. 24, 2008, pp. 7286-95. |
| Francesconi M, Remondini D, Neretti N, Sedivy JM, Cooper LN, Verondini E, Milanesi L, Castellani G. "Reconstructing networks of pathways via significance analysis of their intersections." BMC Bioinformatics, vol. 9 Suppl 4, 2008, pp. S9. |
| Klysik J, Theroux SJ, Sedivy JM, Moffit JS, Boekelheide K. "Signaling crossroads: the function of Raf kinase inhibitory protein in cancer, the central nervous system and reproduction." Cellular signalling, vol. 20, no. 1, 2008, pp. 1-9. |
| Morrish F, Neretti N, Sedivy JM, Hockenbery DM. "The oncogene c-Myc coordinates regulation of metabolic networks to enable rapid cell cycle entry." Cell Cycle, vol. 7, no. 8, 2008, pp. 1054-66. |
| Rath O, Park S, Tang HH, Banfield MJ, Brady RL, Lee YC, Dignam JD, Sedivy JM, Kolch W, Yeung KC. "The RKIP (Raf-1 Kinase Inhibitor Protein) conserved pocket binds to the phosphorylated N-region of Raf-1 and inhibits the Raf-1-mediated activated phosphorylation of MEK." Cellular signalling, vol. 20, no. 5, 2008, pp. 935-41. |
| de Magalhães JP, Sedivy JM, Finch CE, Austad SN, Church GM. "A proposal to sequence genomes of unique interest for research on aging." The Journals of Gerontology: Series A, vol. 62, no. 6, 2007, pp. 583-4. |
| Jeyapalan JC, Ferreira M, Sedivy JM, Herbig U. "Accumulation of senescent cells in mitotic tissue of aging primates." Mechanisms of Ageing and Development, vol. 128, no. 1, 2007, pp. 36-44. |
| Schorl C, Sedivy JM. "Analysis of cell cycle phases and progression in cultured mammalian cells." Methods, vol. 41, no. 2, 2007, pp. 143-50. |
| Neretti N, Remondini D, Tatar M, Sedivy JM, Pierini M, Mazzatti D, Powell J, Franceschi C, Castellani GC. "Correlation analysis reveals the emergence of coherence in the gene expression dynamics following system perturbation." BMC Bioinformatics, vol. 8 Suppl 1, 2007, pp. S16. |
| Moffit JS, Boekelheide K, Sedivy JM, Klysik J. "Mice lacking Raf kinase inhibitor protein-1 (RKIP-1) have altered sperm capacitation and reduced reproduction rates with a normal response to testicular injury." Journal of andrology, vol. 28, no. 6, 2007, pp. 883-90. |
| Manley K, Gee GV, Simkevich CP, Sedivy JM, Atwood WJ. "Microarray analysis of glial cells resistant to JCV infection suggests a correlation between viral infection and inflammatory cytokine gene expression." Virology, vol. 366, no. 2, 2007, pp. 394-404. |
| REMONDINI, D., NERETTI, N., FRANCESCHI, C., TIERI, P., SEDIVY, J. M., MILANESI, L., CASTELLANI, G. C. "NETWORKS FROM GENE EXPRESSION TIME SERIES: CHARACTERIZATION OF CORRELATION PATTERNS." International Journal of Bifurcation and Chaos, vol. 17, no. 07, 2007, pp. 2477-2483. |
| Theroux S, Pereira M, Casten KS, Burwell RD, Yeung KC, Sedivy JM, Klysik J. "Raf kinase inhibitory protein knockout mice: expression in the brain and olfaction deficit." Brain Research Bulletin, vol. 71, no. 6, 2007, pp. 559-67. |
| Sedivy JM. "Telomeres limit cancer growth by inducing senescence: long-sought in vivo evidence obtained." Cancer Cell, vol. 11, no. 5, 2007, pp. 389-91. |
| Herbig U, Ferreira M, Condel L, Carey D, Sedivy JM. "Cellular senescence in aging primates." Science, vol. 311, no. 5765, 2006, pp. 1257. |
| Guney I, Sedivy JM. "Cellular senescence, epigenetic switches and c-Myc." Cell Cycle, vol. 5, no. 20, 2006, pp. 2319-23. |
| Lee HC, Tian B, Sedivy JM, Wands JR, Kim M. "Loss of Raf kinase inhibitor protein promotes cell proliferation and migration of human hepatoma cells." Gastroenterology, vol. 131, no. 4, 2006, pp. 1208-17. |
| Manley K, O'hara BA, Gee GV, Simkevich CP, Sedivy JM, Atwood WJ. "NFAT4 is required for JC virus infection of glial cells." Journal of Virology, vol. 80, no. 24, 2006, pp. 12079-85. |
| Guney I, Wu S, Sedivy JM. "Reduced c-Myc signaling triggers telomere-independent senescence by regulating Bmi-1 and p16(INK4a)." Proceedings of the National Academy of Sciences, vol. 103, no. 10, 2006, pp. 3645-50. |
| Herbig U, Sedivy JM. "Regulation of growth arrest in senescence: telomere damage is not the end of the story." Mechanisms of Ageing and Development, vol. 127, no. 1, 2006, pp. 16-24. |
| Sheffler, W., Upfal, E., Sedivy, J., Noble, W.S. "A learned comparative expression measure for Affymetrix genechip DNA microarrays." 2005 IEEE Computational Systems Bioinformatics Conference (CSB'05), 2005. |
| Sheffler W, Upfal E, Sedivy J, Noble WS. "A learned comparative expression measure for affymetrix genechip DNA microarrays." Proceedings / IEEE Computational Systems Bioinformatics Conference, CSB. IEEE Computational Systems Bioinformatics Conference, 2005, pp. 144-54. |
| Rothermund K, Rogulski K, Fernandes E, Whiting A, Sedivy J, Pu L, Prochownik EV. "C-Myc-independent restoration of multiple phenotypes by two C-Myc target genes with overlapping functions." Cancer Research, vol. 65, no. 6, 2005, pp. 2097-107. |
| Kujoth GC, Hiona A, Pugh TD, Someya S, Panzer K, Wohlgemuth SE, Hofer T, Seo AY, Sullivan R, Jobling WA, Morrow JD, Van Remmen H, Sedivy JM, Yamasoba T, Tanokura M, Weindruch R, Leeuwenburgh C, Prolla TA. "Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging." Science, vol. 309, no. 5733, 2005, pp. 481-4. |
| Muñoz-Alonso MJ, Acosta JC, Richard C, Delgado MD, Sedivy J, León J. "p21Cip1 and p27Kip1 induce distinct cell cycle effects and differentiation programs in myeloid leukemia cells." Journal of Biological Chemistry, vol. 280, no. 18, 2005, pp. 18120-9. |
| Tamura K, Hua B, Adachi S, Guney I, Kawauchi J, Morioka M, Tamamori-Adachi M, Tanaka Y, Nakabeppu Y, Sunamori M, Sedivy JM, Kitajima S. "Stress response gene ATF3 is a target of c-myc in serum-induced cell proliferation." EMBO J, vol. 24, no. 14, 2005, pp. 2590-601. |
| Remondini D, O'Connell B, Intrator N, Sedivy JM, Neretti N, Castellani GC, Cooper LN. "Targeting c-Myc-activated genes with a correlation method: detection of global changes in large gene expression network dynamics." Proceedings of the National Academy of Sciences, vol. 102, no. 19, 2005, pp. 6902-6. |
| Smith KP, Byron M, O'Connell BC, Tam R, Schorl C, Guney I, Hall LL, Agrawal P, Sedivy JM, Lawrence JB. "c-Myc localization within the nucleus: evidence for association with the PML nuclear body." Journal of cellular biochemistry, vol. 93, no. 6, 2004, pp. 1282-96. |
| Hindley AD, Park S, Wang L, Shah K, Wang Y, Hu X, Shokat KM, Kolch W, Sedivy JM, Yeung KC. "Engineering the serine/threonine protein kinase Raf-1 to utilise an orthogonal analogue of ATP substituted at the N6 position." FEBS Letters, vol. 556, no. 1-3, 2004, pp. 26-34. |
| Csoka AB, English SB, Simkevich CP, Ginzinger DG, Butte AJ, Schatten GP, Rothman FG, Sedivy JM. "Genome-scale expression profiling of Hutchinson-Gilford progeria syndrome reveals widespread transcriptional misregulation leading to mesodermal/mesenchymal defects and accelerated atherosclerosis." Aging Cell, vol. 3, no. 4, 2004, pp. 235-43. |
| Charrier-Savournin FB, Château MT, Gire V, Sedivy J, Piette J, Dulic V. "p21-Mediated nuclear retention of cyclin B1-Cdk1 in response to genotoxic stress." Molecular biology of the cell, vol. 15, no. 9, 2004, pp. 3965-76. |
| Chatterjee D, Bai Y, Wang Z, Beach S, Mott S, Roy R, Braastad C, Sun Y, Mukhopadhyay A, Aggarwal BB, Darnowski J, Pantazis P, Wyche J, Fu Z, Kitagwa Y, Keller ET, Sedivy JM, Yeung KC. "RKIP sensitizes prostate and breast cancer cells to drug-induced apoptosis." Journal of Biological Chemistry, vol. 279, no. 17, 2004, pp. 17515-23. |
| Martin-Ruiz C, Saretzki G, Petrie J, Ladhoff J, Jeyapalan J, Wei W, Sedivy J, von Zglinicki T. "Stochastic variation in telomere shortening rate causes heterogeneity of human fibroblast replicative life span." Journal of Biological Chemistry, vol. 279, no. 17, 2004, pp. 17826-33. |
| Herbig U, Jobling WA, Chen BP, Chen DJ, Sedivy JM. "Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a)." Molecular Cell, vol. 14, no. 4, 2004, pp. 501-13. |
| O'Connell BC, Cheung AF, Simkevich CP, Tam W, Ren X, Mateyak MK, Sedivy JM. "A large scale genetic analysis of c-Myc-regulated gene expression patterns." Journal of Biological Chemistry, vol. 278, no. 14, 2003, pp. 12563-73. |
| Wei W, Jobling WA, Chen W, Hahn WC, Sedivy JM. "Abolition of cyclin-dependent kinase inhibitor p16Ink4a and p21Cip1/Waf1 functions permits Ras-induced anchorage-independent growth in telomerase-immortalized human fibroblasts." Molecular and Cellular Biology, vol. 23, no. 8, 2003, pp. 2859-70. |
| Collins CJ, Sedivy JM. "Involvement of the INK4a/Arf gene locus in senescence." Aging Cell, vol. 2, no. 3, 2003, pp. 145-50. |
| Ma W, Hommel C, Brenneisen P, Peters T, Smit N, Sedivy J, Scharffetter-Kochanek K, Wlaschek M. "Long-term growth arrest of PUVA-treated fibroblasts in G2/M in the absence of p16(INK4a) p21(CIP1) or p53." Experimental Dermatology, vol. 12, no. 5, 2003, pp. 629-37. |
| Schorl C, Sedivy JM. "Loss of protooncogene c-Myc function impedes G1 phase progression both before and after the restriction point." Molecular biology of the cell, vol. 14, no. 3, 2003, pp. 823-35. |
| Wei W, Herbig U, Wei S, Dutriaux A, Sedivy JM. "Loss of retinoblastoma but not p16 function allows bypass of replicative senescence in human fibroblasts." EMBO reports, vol. 4, no. 11, 2003, pp. 1061-6. |
| Lindvall C, Hou M, Komurasaki T, Zheng C, Henriksson M, Sedivy JM, Björkholm M, Teh BT, Nordenskjöld M, Xu D. "Molecular characterization of human telomerase reverse transcriptase-immortalized human fibroblasts by gene expression profiling: activation of the epiregulin gene." Cancer Research, vol. 63, no. 8, 2003, pp. 1743-7. |
| Junqueira D, Cilenti L, Musumeci L, Sedivy JM, Zervos AS. "Random mutagenesis of PDZ(Omi) domain and selection of mutants that specifically bind the Myc proto-oncogene and induce apoptosis." Oncogene, vol. 22, no. 18, 2003, pp. 2772-81. |
| Herbig U, Wei W, Dutriaux A, Jobling WA, Sedivy JM. "Real-time imaging of transcriptional activation in live cells reveals rapid up-regulation of the cyclin-dependent kinase inhibitor gene CDKN1A in replicative cellular senescence." Aging Cell, vol. 2, no. 6, 2003, pp. 295-304. |
| Sedivy JM. "Reproductive cloning conserves cellular senescence." J. Geophys. Res., vol. 5, no. 6, 2003, pp. 495-6. |
| Hemmer R, Wei W, Dutriaux A, Sedivy J. "Somatic cell knockouts of tumor suppressor genes." Methods in Molecular Biology, vol. 223, 2003, pp. 187-206. |
| Sedivy JM, Shippen DE, Shakirov EV. "Surprise ending." Nature Genetics, vol. 33, no. 2, 2003, pp. 114-6. |
| Young JI, Sedivy JM, Smith JR. "Telomerase expression in normal human fibroblasts stabilizes DNA 5-methylcytosine transferase I." Journal of Biological Chemistry, vol. 278, no. 22, 2003, pp. 19904-8. |
| Nikiforov MA, Chandriani S, O'Connell B, Petrenko O, Kotenko I, Beavis A, Sedivy JM, Cole MD. "A functional screen for Myc-responsive genes reveals serine hydroxymethyltransferase, a major source of the one-carbon unit for cell metabolism." Molecular and Cellular Biology, vol. 22, no. 16, 2002, pp. 5793-800. |
| You Z, Madrid LV, Saims D, Sedivy J, Wang CY. "c-Myc sensitizes cells to tumor necrosis factor-mediated apoptosis by inhibiting nuclear factor kappa B transactivation." Journal of Biological Chemistry, vol. 277, no. 39, 2002, pp. 36671-7. |
| Raderschall E, Bazarov A, Cao J, Lurz R, Smith A, Mann W, Ropers HH, Sedivy JM, Golub EI, Fritz E, Haaf T. "Formation of higher-order nuclear Rad51 structures is functionally linked to p21 expression and protection from DNA damage-induced apoptosis." Journal of cell science, vol. 115, no. Pt 1, 2002, pp. 153-64. |
| Sedivy JM. "Gene targeting comes to top-down drug screens." Trends in biotechnology, vol. 20, no. 3, 2002, pp. 92-3. |
| Wang Z, Bhattacharya N, Mixter PF, Wei W, Sedivy J, Magnuson NS. "Phosphorylation of the cell cycle inhibitor p21Cip1/WAF1 by Pim-1 kinase." Biochimica et biophysica acta, vol. 1593, no. 1, 2002, pp. 45-55. |
| Obaya AJ, Sedivy JM. "Regulation of cyclin-Cdk activity in mammalian cells." Cellular and molecular life sciences : CMLS, vol. 59, no. 1, 2002, pp. 126-42. |
| Han Z, Wei W, Dunaway S, Darnowski JW, Calabresi P, Sedivy J, Hendrickson EA, Balan KV, Pantazis P, Wyche JH. "Role of p21 in apoptosis and senescence of human colon cancer cells treated with camptothecin." Journal of Biological Chemistry, vol. 277, no. 19, 2002, pp. 17154-60. |
| Bunz F, Fauth C, Speicher MR, Dutriaux A, Sedivy JM, Kinzler KW, Vogelstein B, Lengauer C. "Targeted inactivation of p53 in human cells does not result in aneuploidy." Cancer Research, vol. 62, no. 4, 2002, pp. 1129-33. |
| Obaya AJ, Kotenko I, Cole MD, Sedivy JM. "The proto-oncogene c-myc acts through the cyclin-dependent kinase (Cdk) inhibitor p27(Kip1) to facilitate the activation of Cdk4/6 and early G(1) phase progression." Journal of Biological Chemistry, vol. 277, no. 34, 2002, pp. 31263-9. |
| Bazarov AV, Adachi S, Li SF, Mateyak MK, Wei S, Sedivy JM. "A modest reduction in c-myc expression has minimal effects on cell growth and apoptosis but dramatically reduces susceptibility to Ras and Raf transformation." Cancer Research, vol. 61, no. 3, 2001, pp. 1178-86. |
| Adachi S, Obaya AJ, Han Z, Ramos-Desimone N, Wyche JH, Sedivy JM. "c-Myc is necessary for DNA damage-induced apoptosis in the G(2) phase of the cell cycle." Molecular and Cellular Biology, vol. 21, no. 15, 2001, pp. 4929-37. |
| Soucie EL, Annis MG, Sedivy J, Filmus J, Leber B, Andrews DW, Penn LZ. "Myc potentiates apoptosis by stimulating Bax activity at the mitochondria." Molecular and Cellular Biology, vol. 21, no. 14, 2001, pp. 4725-36. |
| Yeung KC, Rose DW, Dhillon AS, Yaros D, Gustafsson M, Chatterjee D, McFerran B, Wyche J, Kolch W, Sedivy JM. "Raf kinase inhibitor protein interacts with NF-kappaB-inducing kinase and TAK1 and inhibits NF-kappaB activation." Molecular and Cellular Biology, vol. 21, no. 21, 2001, pp. 7207-17. |
| Wei W, Hemmer RM, Sedivy JM. "Role of p14(ARF) in replicative and induced senescence of human fibroblasts." Molecular and Cellular Biology, vol. 21, no. 20, 2001, pp. 6748-57. |
| Bowman T, Broome MA, Sinibaldi D, Wharton W, Pledger WJ, Sedivy JM, Irby R, Yeatman T, Courtneidge SA, Jove R. "Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis." Proceedings of the National Academy of Sciences, vol. 98, no. 13, 2001, pp. 7319-24. |
| Sedivy JM. "The cellular immortalization process: relevant issues for the generation of cell substrates for production of vaccines and other biologicals." Developments in biologicals, vol. 106, 2001, pp. 479-86; discussion 486-8, 501-11. |
| Hermeking H, Rago C, Schuhmacher M, Li Q, Barrett JF, Obaya AJ, O'Connell BC, Mateyak MK, Tam W, Kohlhuber F, Dang CV, Sedivy JM, Eick D, Vogelstein B, Kinzler KW. "Identification of CDK4 as a target of c-MYC." Proceedings of the National Academy of Sciences, vol. 97, no. 5, 2000, pp. 2229-34. |
| Yeung K, Janosch P, McFerran B, Rose DW, Mischak H, Sedivy JM, Kolch W. "Mechanism of suppression of the Raf/MEK/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein." Molecular and Cellular Biology, vol. 20, no. 9, 2000, pp. 3079-85. |
| Oster SK, Marhin WW, Asker C, Facchini LM, Dion PA, Funa K, Post M, Sedivy JM, Penn LZ. "Myc is an essential negative regulator of platelet-derived growth factor beta receptor expression." Molecular and Cellular Biology, vol. 20, no. 18, 2000, pp. 6768-78. |
| Landay M, Oster SK, Khosravi F, Grove LE, Yin X, Sedivy J, Penn LZ, Prochownik EV. "Promotion of growth and apoptosis in c-myc nullizygous fibroblasts by other members of the myc oncoprotein family." Cell death and differentiation, vol. 7, no. 8, 2000, pp. 697-705. |
| Mateyak MK, Obaya AJ, Sedivy JM. "c-Myc regulates cyclin D-Cdk4 and -Cdk6 activity but affects cell cycle progression at multiple independent points." Molecular and Cellular Biology, vol. 19, no. 7, 1999, pp. 4672-83. |
| Wei W, Sedivy JM. "Differentiation between senescence (M1) and crisis (M2) in human fibroblast cultures." Experimental Cell Research, vol. 253, no. 2, 1999, pp. 519-22. |
| Wei S, Wei S, Sedivy JM. "Expression of catalytically active telomerase does not prevent premature senescence caused by overexpression of oncogenic Ha-Ras in normal human fibroblasts." Cancer Research, vol. 59, no. 7, 1999, pp. 1539-43. |
| Sedivy JM, Dutriaux A. "Gene targeting and somatic cell genetics--a rebirth or a coming of age?." Trends in Genetics, vol. 15, no. 3, 1999, pp. 88-90. |
| Obaya AJ, Mateyak MK, Sedivy JM. "Mysterious liaisons: the relationship between c-Myc and the cell cycle." Oncogene, vol. 18, no. 19, 1999, pp. 2934-41. |
| Chuang YY, Chen Q, Brown JP, Sedivy JM, Liber HL. "Radiation-induced mutations at the autosomal thymidine kinase locus are not elevated in p53-null cells." Cancer Research, vol. 59, no. 13, 1999, pp. 3073-6. |
| Yeung K, Seitz T, Li S, Janosch P, McFerran B, Kaiser C, Fee F, Katsanakis KD, Rose DW, Mischak H, Sedivy JM, Kolch W. "Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP." J. Geophys. Res., vol. 401, no. 6749, 1999, pp. 173-7. |
| Bush A, Mateyak M, Dugan K, Obaya A, Adachi S, Sedivy J, Cole M. "c-myc null cells misregulate cad and gadd45 but not other proposed c-Myc targets." Genes & Development, vol. 12, no. 24, 1998, pp. 3797-802. |
| Sedivy JM. "Can ends justify the means?: telomeres and the mechanisms of replicative senescence and immortalization in mammalian cells." Proceedings of the National Academy of Sciences, vol. 95, no. 16, 1998, pp. 9078-81. |
| Counter CM, Hahn WC, Wei W, Caddle SD, Beijersbergen RL, Lansdorp PM, Sedivy JM, Weinberg RA. "Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization." Proceedings of the National Academy of Sciences, vol. 95, no. 25, 1998, pp. 14723-8. |
| Shichiri M, Sedivy JM, Marumo F, Hirata Y. "Endothelin-1 is a potent survival factor for c-Myc-dependent apoptosis." Molecular endocrinology (Baltimore, Md.), vol. 12, no. 2, 1998, pp. 172-80. |
| Lu KK, Bazarov AV, Yoon LS, Sedivy JM. "Isolation of temperature-sensitive mutations in the c-raf-1 catalytic domain and expression of conditionally active and dominant-defective forms of Raf-1 in cultured mammalian cells." Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research, vol. 9, no. 5, 1998, pp. 367-80. |
| Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown JP, Sedivy JM, Kinzler KW, Vogelstein B. "Requirement for p53 and p21 to sustain G2 arrest after DNA damage." Science, vol. 282, no. 5393, 1998, pp. 1497-501. |
| Prouty SM, Maroo A, Maucher C, Mischak H, Kolch W, Sedivy JM. "Studies of perinuclear and nuclear translocation of the Raf-1 protein in rodent fibroblasts." Biochimica et biophysica acta, vol. 1402, no. 1, 1998, pp. 6-16. |
| Xiao Q, Claassen G, Shi J, Adachi S, Sedivy J, Hann SR. "Transactivation-defective c-MycS retains the ability to regulate proliferation and apoptosis." Genes & Development, vol. 12, no. 24, 1998, pp. 3803-8. |
| Shichiri M, Adachi S, Sedivy JM, Marumo F, Hirata Y. "Biphasic regulation of the preproendothelin-1 gene by c-myc." Endocrinology, vol. 138, no. 11, 1997, pp. 4584-90. |
| Brown JP, Wei W, Sedivy JM. "Bypass of senescence after disruption of p21CIP1/WAF1 gene in normal diploid human fibroblasts." Science, vol. 277, no. 5327, 1997, pp. 831-4. |
| Weissinger EM, Eissner G, Grammer C, Fackler S, Haefner B, Yoon LS, Lu KS, Bazarov A, Sedivy JM, Mischak H, Kolch W. "Inhibition of the Raf-1 kinase by cyclic AMP agonists causes apoptosis of v-abl-transformed cells." Molecular and Cellular Biology, vol. 17, no. 6, 1997, pp. 3229-41. |
| Mateyak MK, Obaya AJ, Adachi S, Sedivy JM. "Phenotypes of c-Myc-deficient rat fibroblasts isolated by targeted homologous recombination." Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research, vol. 8, no. 10, 1997, pp. 1039-48. |
| Janosch P, Schellerer M, Seitz T, Reim P, Eulitz M, Brielmeier M, Kölch W, Sedivy JM, Mischak H. "Characterization of IkappaB kinases. IkappaB-alpha is not phosphorylated by Raf-1 or protein kinase C isozymes, but is a casein kinase II substrate." Journal of Biological Chemistry, vol. 271, no. 23, 1996, pp. 13868-74. |
| Hanson KD, Sedivy JM. "Analysis of biological selections for high-efficiency gene targeting." Molecular and Cellular Biology, vol. 15, no. 1, 1995, pp. 45-51. |
| Yang TA, Heiser WC, Sedivy JM. "Efficient in situ electroporation of mammalian cells grown on microporous membranes." Nucleic acids research, vol. 23, no. 15, 1995, pp. 2803-10. |
| Li S, Janosch P, Tanji M, Rosenfeld GC, Waymire JC, Mischak H, Kolch W, Sedivy JM. "Regulation of Raf-1 kinase activity by the 14-3-3 family of proteins." EMBO J, vol. 14, no. 4, 1995, pp. 685-96. |
| Hanson KD, Shichiri M, Follansbee MR, Sedivy JM. "Effects of c-myc expression on cell cycle progression." Molecular and Cellular Biology, vol. 14, no. 9, 1994, pp. 5748-55. |
| Prouty SM, Hanson KD, Boyle AL, Brown JR, Shichiri M, Follansbee MR, Kang W, Sedivy JM. "A cell culture model system for genetic analyses of the cell cycle by targeted homologous recombination." Oncogene, vol. 8, no. 4, 1993, pp. 899-907. |
| Shichiri M, Hanson KD, Sedivy JM. "Effects of c-myc expression on proliferation, quiescence, and the G0 to G1 transition in nontransformed cells." Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research, vol. 4, no. 2, 1993, pp. 93-104. |
| Karantza V, Maroo A, Fay D, Sedivy JM. "Overproduction of Rb protein after the G1/S boundary causes G2 arrest." Molecular and Cellular Biology, vol. 13, no. 11, 1993, pp. 6640-52. |
| Li S, Sedivy JM. "Raf-1 protein kinase activates the NF-kappa B transcription factor by dissociating the cytoplasmic NF-kappa B-I kappa B complex." Proceedings of the National Academy of Sciences, vol. 90, no. 20, 1993, pp. 9247-51. |
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Sedivy, J.M., Joyner, A.
Gene Targeting. Oxford University Press, 1992.
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Sedivy, J.M.
"Pilot scale protein production using inducible gene amplification." Animal Cell Culture and Production of Biologicals, edited by Sasaki, R., Ikura, K., New York, Dordrecht, Heidelberg, London, Kluwer, 1991, pp. 251-258.
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| Leonardo ED, Sedivy JM. "A new vector for cloning large eukaryotic DNA segments in Escherichia coli." Bio/technology (Nature Publishing Company), vol. 8, no. 9, 1990, pp. 841-4. |
| Schnipper LE, Chan V, Sedivy J, Jat P, Sharp PA. "Gene activation by induced DNA rearrangements." Cancer Research, vol. 49, no. 23, 1989, pp. 6640-4. |
| Sedivy JM, Sharp PA. "Positive genetic selection for gene disruption in mammalian cells by homologous recombination." Proceedings of the National Academy of Sciences, vol. 86, no. 1, 1989, pp. 227-31. |
| Sedivy, J.M. "New genetic methods for mammalian cells." Bio/technology (Nature Publishing Company), vol. 6, 1988, pp. 1192-1196. |
| Sedivy JM, Capone JP, RajBhandary UL, Sharp PA. "An inducible mammalian amber suppressor: propagation of a poliovirus mutant." Cell, vol. 50, no. 3, 1987, pp. 379-89. |
| Sedivy JM, Babul J, Fraenkel DG. "AMP-insensitive fructose bisphosphatase in Escherichia coli and its consequences." Proceedings of the National Academy of Sciences, vol. 83, no. 6, 1986, pp. 1656-9. |
| Capone JP, Sedivy JM, Sharp PA, RajBhandary UL. "Introduction of UAG, UAA, and UGA nonsense mutations at a specific site in the Escherichia coli chloramphenicol acetyltransferase gene: use in measurement of amber, ochre, and opal suppression in mammalian cells." Molecular and Cellular Biology, vol. 6, no. 9, 1986, pp. 3059-67. |
| Sedivy JM, Fraenkel DG. "Fructose bisphosphatase of Saccharomyces cerevisiae. Cloning, disruption and regulation of the FBP1 structural gene." Journal of molecular biology, vol. 186, no. 2, 1985, pp. 307-19. |
| Sedivy JM, Daldal F, Fraenkel DG. "Fructose bisphosphatase of Escherichia coli: cloning of the structural gene (fbp) and preparation of a chromosomal deletion." Journal of bacteriology, vol. 158, no. 3, 1984, pp. 1048-53. |
| Geisselsoder J, Sedivy JM, Walsh RB, Goldstein R. "Capsid structure of satellite phage P4 and its P2 helper." Journal of ultrastructure research, vol. 79, no. 2, 1982, pp. 165-73. |
| Goldstein R, Sedivy J, Ljungquist E. "Propagation of satellite phage P4 as a plasmid." Proceedings of the National Academy of Sciences, vol. 79, no. 2, 1982, pp. 515-9. |
De Cecco, M., Criscione, S.W., Peckham, E.J., Hillenmeyer, S., Hamm, E.A., Manivannan, J., Peterson, A.L., Kreiling, J.A., Neretti, N. and Sedivy, J.M. (2013). Genomes of replicatively senescent cells undergo global epigenetic changes leading to gene silencing and activation of transposable elements. Aging Cell 12: 247-256 (PMID 23360310; PMCID 3618682).
Kreiling, J.A., Tamamori-Adachi, M., Sexton, A.N., Jeyapalan, J.C., Munoz-Najar, U., Peterson, A.L., Manivannan, J., Rogers, E.S., Pchelintsev, N.A., Adams, P.D. and Sedivy, J.M. (2011). Age-associated increase in heterochromatic marks in murine and primate tissues. Aging Cell 10: 292-304 (PMID: 21176091; PMCID 3079313).
Guney, I., Wu, S. and Sedivy, J.M. (2006). Reduced c-Myc signaling triggers telomere-independent senescence by regulating the polycomb repressor Bmi-1 and the CDK inhibitor p16INK4a. Proc. Natl. Acad. Sci. USA 103: 3645-3650 (PMID: 16537449).
Herbig, U., Ferreira, M., Condel, L., Carey, D. and Sedivy, J.M. (2006). Cellular senescence in aging primates. Science 311: 1257 (PMID: 16456035).
Remondini, D., O'Connell, B., Intrator, N., Sedivy, J.M., Neretti, N., Castellani, G.C. and Cooper, L.N. (2005). Targeting c-Myc activated genes via a correlation method: detection of global changes in large gene expression network dynamics. Proc. Natl. Acad. Sci. USA 102: 6902-6906.
Herbig, U., Jobling, W.A., Chen, B.P.C., Chen, D.J. and Sedivy, J.M. (2004). Telomere shortening triggers replicative senescence of human cells through a signaling pathway involving ATM, p53 and p21CIP1 but not p16INK4a. Mol. Cell 14: 501-513.
Wei, W., Jobling, W.A., Chen, W., Hahn, W.C. and Sedivy, J.M. (2003). Abolition of cyclin-dependent kinase inhibitors p16Ink4a and p21Cip1/Waf1 functions permits Ras-induced anchorage-independent growth in telomerase-immortalized human fibroblasts. Mol. Cell. Biol. 23: 2859-2870.
Yeung, K.C., Rose, D.W., Dhillon, A.S., Yaros, D., Gustafsson, M., Chatterjee, D., McFerran, B., Wyche, J., Kolch, W. and Sedivy, J.M. (2001). Raf kinase inhibitor protein interacts with NF-κB-inducing kinase and TAK1 and inhibits NF-κB activation. Mol Cell. Biol. 21: 7207-7217.
Wei, W., Hemmer, R.M. and Sedivy, J.M. (2001). The role of p14ARF in replicative and induced senescence of human fibroblasts. Mol. Cell. Biol. 21: 6748-6757.
Adachi, S., Obaya, A.J., Han, Z., Ramos-Desimone, N., Wyche, J.H. and Sedivy, J.M. (2001). c-Myc is necessary for DNA damage-induced apoptosis in the G2 phase of the cell cycle. Mol. Cell. Biol. 21: 4929-4937.
Yeung, K.C., Seitz, T., Li, S., Janosch, P., McFerran, B., Kaiser, C., Fee, F., Katsanakis, K.D., Rose, D.W., Mischak, H., Sedivy, J.M. and Kolch, W. (1999). Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP. Nature 401: 173-177.
Mateyak, M.K., Obaya, A.J. and Sedivy, J.M. (1999). c-Myc regulates cyclin D/Cdk4/6 activity but affects cell cycle progression at multiple independent steps. Mol. Cell. Biol. 19: 4672-4683.
Brown, J.P., Wei, W. and Sedivy, J.M. (1997). Bypass of senescence after disruption of p21CIP1/WAF1 gene in normal diploid human fibroblasts. Science 277: 831-834.
Hanson, K.D., and Sedivy, J.M. (1995). Analysis of biological selections for high efficiency gene targeting. Mol. Cell. Biol. 15: 45-51.
Sedivy, J.M. and Sharp, P.A. (1989). Positive genetic selection for gene disruption in mammalian cells by homologous recombination. Proc. Natl. Acad. Sci. USA 86: 227-231.
Sedivy, J.M., Capone, J.P., RajBhandary, U.L. and Sharp, P.A. (1987). An inducible mammalian amber suppressor: propagation of a poliovirus mutant. Cell 50: 379-389.
| Year | Degree | Institution |
|---|---|---|
| 1985 | PhD | Harvard University |
| 1978 | BSc | University of Toronto |
| Name | Title |
|---|---|
| Kreiling, Jill | Associate Professor of Molecular Biology, Cell Biology and Biochemistry (Research) |
| Neretti, Nicola | Associate Professor of Molecular Biology, Cell Biology, and Biochemistry, Associate Director for the Center on the Biology of Aging |
| Tatar, Marc | Professor of Biology |
| BIOL 2030 - Foundations for Advanced Study in the Life Sciences |
| BIOL 2350 - The Biology of Aging |
