DF/HCC Program Affiliation

Cancer Cell Biology
Cancer Genetics

Research Abstract

We use genomic systems biology to model
regulatory and enzymatic networks in mammalian and microbial cells. We develop technologies based on DNA-arrays, mass-spectrometry, automated microfluidics, polonies, and homologous recombination genome engineering. We have used these to discover genes affectng cell proliferation, alternative RNA splicing, and new regulatory sites involved in cell-cycle control and stress responses. We have developed integrated gene expression and functional genomics databases. For additional information see http://arep.med.harvard.edu.

Publications

• de Magalhães JP, Church GM.Analyses of human-chimpanzee orthologous gene pairs to explore evolutionary hypotheses of aging.Mech Ageing Dev 2007 Mar 25.
  17459455
• de Magalhães JP, Costa J, Church GM.An analysis of the relationship between metabolism, developmental schedules, and longevity using phylogenetic independent contrasts.J Gerontol A Biol Sci Med Sci 2007 Feb;62(2):149-60.
  17339640
• Yang A, Zhu Z, Kapranov P, McKeon F, Church GM, Gingeras TR, Struhl K.Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells.Mol Cell 2006 Nov 17;24(4):593-602.
  17188034
• Reppas NB, Wade JT, Church GM, Struhl K.The transition between transcriptional initiation and elongation in E. coli is highly variable and often rate limiting.Mol Cell 2006 Dec 8;24(5):747-57.
  17157257
• Forster AC, Church GM.Synthetic biology projects in vitro.Genome Res 2007 Jan;17(1):1-6.
  17151344
• Tolonen AC, Aach J, Lindell D, Johnson ZI, Rector T, Steen R, Church GM, Chisholm SW.Global gene expression of Prochlorococcus ecotypes in response to changes in nitrogen availability.Mol Syst Biol 2006;2:53.
  17016519
• Derti A, Roth FP, Church GM, Wu CT.Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants.Nat Genet 2006 Oct;38(10):1216-20.
  16998490
• Lee SI, Pe'er D, Dudley AM, Church GM, Koller D.Identifying regulatory mechanisms using individual variation reveals key role for chromatin modification.Proc Natl Acad Sci U S A 2006 Sep 19;103(38):14062-7.
  16968785
• Forster AC, Church GM.Towards synthesis of a minimal cell.Mol Syst Biol 2006;2:45.
  16924266
• Jaffe JD, Mani DR, Leptos KC, Church GM, Gillette MA, Carr SA.PEPPeR: A platform for experimental proteomic pattern recognition.Mol Cell Proteomics 2006 Jul 19.
  16857664
• Kuo WP, Liu F, Trimarchi J, Punzo C, Lombardi M, Sarang J, Whipple ME, Maysuria M, Serikawa K, Lee SY, McCrann D, Kang J, Shearstone JR, Burke J, Park DJ, Wang X, Rector TL, Ricciardi-Castagnoli P, Perrin S, Choi S, Bumgarner R, Kim JH, Short GF 3rd, Free
  16823376
• Zhang K, Martiny AC, Reppas NB, Barry KW, Malek J, Chisholm SW, Church GM.Sequencing genomes from single cells by polymerase cloning.Nat Biotechnol 2006 Jun;24(6):680-6.
  16732271
• Church GM.From systems biology to synthetic biology.Mol Syst Biol 2005;1:2005.0032.
  16729067
• Church GM.The personal genome project.Mol Syst Biol 2005;1:2005.0030.
  16729065
• Dudley AM, Janse DM, Tanay A, Shamir R, Church GM.A global view of pleiotropy and phenotypically derived gene function in yeast.Mol Syst Biol 2005;1:2005.0001.
  16729036
• Kharchenko P, Chen L, Freund Y, Vitkup D, Church GM.Identifying metabolic enzymes with multiple types of association evidence.BMC Bioinformatics 2006;7:177.
  16571130
• Zhang K, Zhu J, Shendure J, Porreca GJ, Aach JD, Mitra RD, Church GM.Long-range polony haplotyping of individual human chromosome molecules.Nat Genet 2006 Mar;38(3):382-7.
  16493423
• de Magalhães JP, Church GM.Cells discover fire: employing reactive oxygen species in development and consequences for aging.Exp Gerontol 2006 Jan;41(1):1-10.
  16226003
• Shendure J, Porreca GJ, Reppas NB, Lin X, McCutcheon JP, Rosenbaum AM, Wang MD, Zhang K, Mitra RD, Church GM.Accurate multiplex polony sequencing of an evolved bacterial genome.Science 2005 Sep 9;309(5741):1728-32.
  16081699
• Zhu Z, Shendure J, Church GM.Discovering functional transcription-factor combinations in the human cell cycle.Genome Res 2005 Jun;15(6):848-55.
  15930495
• Tian J, Gong H, Sheng N, Zhou X, Gulari E, Gao X, Church G.Accurate multiplex gene synthesis from programmable DNA microchips.Nature 2004 Dec 23;432(7020):1050-4.
  15616567
• Zhu J, Shendure J, Mitra RD, Church GM.Single molecule profiling of alternative pre-mRNA splicing.Science 2003 Aug 8;301(5634):836-8.
  12907803
• Dantas G, Sommer MO, Oluwasegun RD, Church GM.Bacteria subsisting on antibiotics.Science 2008 Apr 4;320(5872):100-3.
  18388292
• Kettler GC, Martiny AC, Huang K, Zucker J, Coleman ML, Rodrigue S, Chen F, Lapidus A, Ferriera S, Johnson J, Steglich C, Church GM, Richardson P, Chisholm SW.Patterns and implications of gene gain and loss in the evolution of Prochlorococcus.PLoS Genet 20
  18159947
• Bang D, Church GM.Gene synthesis by circular assembly amplification.Nat Methods 2008 Jan;5(1):37-9.
  18037891
• Porreca GJ, Zhang K, Li JB, Xie B, Austin D, Vassallo SL, LeProust EM, Peck BJ, Emig CJ, Dahl F, Gao Y, Church GM, Shendure J.Multiplex amplification of large sets of human exons.Nat Methods 2007 Nov;4(11):931-6.
  17934468
• Lindell D, Jaffe JD, Coleman ML, Futschik ME, Axmann IM, Rector T, Kettler G, Sullivan MB, Steen R, Hess WR, Church GM, Chisholm SW.Genome-wide expression dynamics of a marine virus and host reveal features of co-evolution.Nature 2007 Sep 6;449(7158):83-6
  17805294
• Conrad C, Zhu J, Conrad C, Schoenfeld D, Fang Z, Ingelsson M, Stamm S, Church G, Hyman BT.Single molecule profiling of tau gene expression in Alzheimer's disease.J Neurochem 2007 Nov;103(3):1228-36.
  17727636
• de Magalhaes JP, Sedivy JM, Finch CE, Austad SN, Church GM.A proposal to sequence genomes of unique interest for research on aging.J Gerontol A Biol Sci Med Sci 2007 Jun;62(6):583-4.
  17595413
• Bakal C, Aach J, Church G, Perrimon N.Quantitative morphological signatures define local signaling networks regulating cell morphology.Science 2007 Jun 22;316(5832):1753-6.
  17588932
• Wright MA, Kharchenko P, Church GM, Segre D.Chromosomal periodicity of evolutionarily conserved gene pairs.Proc Natl Acad Sci U S A 2007 Jun 19;104(25):10559-64.
  17563360
• Kim JB, Porreca GJ, Song L, Greenway SC, Gorham JM, Church GM, Seidman CE, Seidman JG.Polony multiplex analysis of gene expression (PMAGE) in mouse hypertrophic cardiomyopathy.Science 2007 Jun 8;316(5830):1481-4.
  17556586
• Bugl H, Danner JP, Molinari RJ, Mulligan JT, Park HO, Reichert B, Roth DA, Wagner R, Budowle B, Scripp RM, Smith JA, Steele SJ, Church G, Endy D.DNA synthesis and biological security.Nat Biotechnol 2007 Jun;25(6):627-9.
  17557094
• Kharchenko P, Church GM, Vitkup D.Expression dynamics of a cellular metabolic network.Mol Syst Biol 2005;1:2005.0016.
  16729051
• Estrada B, Choe SE, Gisselbrecht SS, Michaud S, Raj L, Busser BW, Halfon MS, Church GM, Michelson AM.An integrated strategy for analyzing the unique developmental programs of different myoblast subtypes.PLoS Genet 2006 Feb;2(2):e16.
  16482229
• Leptos KC, Sarracino DA, Jaffe JD, Krastins B, Church GM.MapQuant: open-source software for large-scale protein quantification.Proteomics 2006 Mar;6(6):1770-82.
  16470651
• Church GM.Genomes for all.Sci Am 2006 Jan;294(1):46-54.
  16468433
• de Magalhães JP, Church GM.Genomes optimize reproduction: aging as a consequence of the developmental program.Physiology (Bethesda) 2005 Aug;20:252-9.
  16024513
• Ahmad QR, Nguyen DH, Wingerd MA, Church GM, Steffen MA.Molecular weight assessment of proteins in total proteome profiles using 1D-PAGE and LC/MS/MS.Proteome Sci 2005 Jun 8;3(1):6.
  15941491
• Kharchenko P, Vitkup D, Church GM.Filling gaps in a metabolic network using expression information.Bioinformatics 2004 Aug 4;20 Suppl 1:I178-I185.
  15262797
• Catic A, Collins C, Church GM, Ploegh HL.Preferred in vivo ubiquitination sites.Bioinformatics 2004 Dec 12;20(18):3302-7.
  15256413
• Mikkilineni V, Mitra RD, Merritt J, DiTonno JR, Church GM, Ogunnaike B, Edwards JS.Digital quantitative measurements of gene expression.Biotechnol Bioeng 2004 Apr 20;86(2):117-24.
  15052631
• Kim J, Krichevsky A, Grad Y, Hayes GD, Kosik KS, Church GM, Ruvkun G.Identification of many microRNAs that copurify with polyribosomes in mammalian neurons.Proc Natl Acad Sci U S A 2004 Jan 6;101(1):360-5.
  14691248
• Mitra RD, Shendure J, Olejnik J, Edyta-Krzymanska-Olejnik , Church GM.Fluorescent in situ sequencing on polymerase colonies.Anal Biochem 2003 Sep 1;320(1):55-65.
  12895469
• Weber G, Shendure J, Tanenbaum DM, Church GM, Meyerson M.Identification of foreign gene sequences by transcript filtering against the human genome.Nat Genet 2002 Feb;30(2):141-2.
  11788827
• Badarinarayana V, Estep PW, Shendure J, Edwards J, Tavazoie S, Lam F, Church GM.Selection analyses of insertional mutants using subgenic-resolution arrays.Nat Biotechnol 2001 Nov;19(11):1060-5.
  11689852
• Pilpel Y, Sudarsanam P, Church GM.Identifying regulatory networks by combinatorial analysis of promoter elements.Nat Genet 2001 Oct;29(2):153-9.
  11547334
• Bulyk ML, Huang X, Choo Y, Church GM.Exploring the DNA-binding specificities of zinc fingers with DNA microarrays.Proc Natl Acad Sci U S A 2001 Jun 19;98(13):7158-63.
  11404456
• Aach J, Bulyk ML, Church GM, Comander J, Derti A, Shendure J.Computational comparison of two draft sequences of the human genome.Nature 2001 Feb 15;409(6822):856-9.
  11237010
• Mitra RD, Church GM.In situ localized amplification and contact replication of many individual DNA molecules.Nucleic Acids Res 1999 Dec 15;27(24):e34.
  10572186
• Tavazoie S, Hughes JD, Campbell MJ, Cho RJ, Church GM.Systematic determination of genetic network architecture.Nat Genet 1999 Jul;22(3):281-5.
  10391217
• Bulyk ML, Gentalen E, Lockhart DJ, Church GM.Quantifying DNA-protein interactions by double-stranded DNA arrays.Nat Biotechnol 1999 Jun;17(6):573-7.
  10385322
• Chen T, He HL, Church GM.Modeling gene expression with differential equations.Pac Symp Biocomput 1999:29-40.
  10380183
• McGuire AM, De Wulf P, Church GM, Lin EC.A weight matrix for binding recognition by the redox-response regulator ArcA-P of Escherichia coli.Mol Microbiol 1999 Apr;32(1):219-21.
  10216875
• Johnson JM, Church GM.Alignment and structure prediction of divergent protein families: periplasmic and outer membrane proteins of bacterial efflux pumps.J Mol Biol 1999 Apr 2;287(3):695-715.
  10092468
• Robison K, McGuire AM, Church GM.A comprehensive library of DNA-binding site matrices for 55 proteins applied to the complete Escherichia coli K-12 genome.J Mol Biol 1998 Nov 27;284(2):241-54.
  9813115
• Roth FP, Hughes JD, Estep PW, Church GM.Finding DNA regulatory motifs within unaligned noncoding sequences clustered by whole-genome mRNA quantitation.Nat Biotechnol 1998 Oct;16(10):939-45.
  9788350
• Tavazoie S, Church GM.Quantitative whole-genome analysis of DNA-protein interactions by in vivo methylase protection in E. coli.Nat Biotechnol 1998 Jun;16(6):566-71.
  9624689
• Link AJ, Phillips D, Church GM.Methods for generating precise deletions and insertions in the genome of wild-type Escherichia coli: application to open reading frame characterization.J Bacteriol 1997 Oct;179(20):6228-37.
  9335267
• Link AJ, Robison K, Church GM.Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12.Electrophoresis 1997 Aug;18(8):1259-313.
  9298646