LOGOResearch Overview

The genomics research laboratory has been formed in September 2009 out of the original Genomics laboratory set up by Ioannis Ragoussis in 2001. Ioannis has played a key role in establishing the WTCHG Next Generation Sequencing Facility including four Illumina GA II and two Roche GSFLX genome analysers. The group currently explores technologies RNA-seq in and genomic segment specific sequencing as part of the Centre's core research programme. The lab is involved in medical resequencing projects in collaboration with the Biomedical Research Centre and genotyping technologies as part of the MalariaGen and EpigenChlamydia consortia. Microarray and next generation sequencing is developed for expression profiling to identify hypoxia regulated transcripts, microRNAs and their targets. Gene regulation is studied by applying ChIP on chip, ChIP-seq and protein binding array technologies for high throughput affinity measurements of the Nf-kB, GATA and IRF family transcription factor proteins as well as Pol II. Further leading applications of the technologies are pursued in collaboration with Oxford Nanolabs. Work on microarray technology linked to microfluidic applications has lead to the generation of molecular diagnostic tools in collaboration with companies such as Oxford Gene Technologies (UK), and LETI (France). Additional funding is received through grants from EU FP6, FP7 programmes, the MRC and others.

Recent Publications

1: Yau C, Mouradov D, Jorissen RN, Colella S, Mirza G, Steers G, Harris A, Ragoussis J, Sieber O, Holmes CC. A statistical approach for detecting genomic aberrations in heterogeneous tumor samples from single nucleotide polymorphism genotyping data. Genome Biol. 2010 Sep 21;11(9):R92. [Epub ahead of print] [PMID: 20858232]

2: Yang J, Jubb AM, Pike L, Buffa FM, Turley H, Baban D, Leek R, Gatter KC, Ragoussis J, Harris AL. The histone demethylase JMJD2B is regulated by estrogen receptor alpha and hypoxia, and is a key mediator of estrogen induced growth. Cancer Res. 2010 Aug 15;70(16):6456-66. Epub 2010 Aug 3. [PMID: 20682797]

3: Pagnamenta AT, Bacchelli E, de Jonge MV, Mirza G, Scerri TS, Minopoli F, Chiocchetti A, Ludwig KU, Hoffmann P, Paracchini S, Lowy E, Harold DH, Chapman JA, Klauck SM, Poustka F, Houben RH, Staal WG, Ophoff RA, O'Donovan MC, Williams J, Nothen MM, Schulte-Korne G, Deloukas P, Ragoussis J, Bailey AJ, Maestrini E, Monaco AP; International Molecular Genetic Study Of Autism Consortium. Characterization of a Family with Rare Deletions in CNTNAP5 and DOCK4 Suggests Novel Risk Loci for Autism and Dyslexia. Biol Psychiatry. 2010 Aug 15;68(4):320-8. [Epub 2010 Mar 26] [PMID: 20346443]

4: Anney R, Klei L, Pinto D, Regan R, Conroy J, Magalhaes TR, Correia C, Abrahams BS, Sykes N, Pagnamenta AT, Almeida J, Bacchelli E, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bölte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Carson AR, Casallo G, Casey J, Chu SH, Cochrane L, Corsello C, Crawford EL, Crossett A, Dawson G, de Jonge M, Delorme R, Drmic I, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Fombonne E, Freitag CM, Gilbert J, Gillberg C, Glessner JT, Goldberg J, Green J, Guter SJ, Hakonarson H, Heron EA, Hill M, Holt R, Howe JL, Hughes G, Hus V, Igliozzi R, Kim C, Klauck SM, Kolevzon A, Korvatska O, Kustanovich V, Lajonchere CM, Lamb JA, Laskawiec M, Leboyer M, Le Couteur A, Leventhal BL, Lionel AC, Liu XQ, Lord C, Lotspeich L, Lund SC, Maestrini E, Mahoney W, Mantoulan C, Marshall CR, McConachie H, McDougle CJ, McGrath J, McMahon WM, Melhem NM, Merikangas A, Migita O, Minshew NJ, Mirza GK, Munson J, Nelson SF, Noakes C, Noor A, Nygren G, Oliveira G, Papanikolaou K, Parr JR, Parrini B, Paton T, Pickles A, Piven J, Posey DJ, Poustka A, Poustka F, Prasad A, Ragoussis J, Renshaw K, Rickaby J, Roberts W, Roeder K, Roge B, Rutter ML, Bierut LJ, Rice JP, Salt J, Sansom K, Sato D, Segurado R, Senman L, Shah N, Sheffield VC, Soorya L, Sousa I, Stoppioni V, Strawbridge C, Tancredi R, Tansey K, Thiruvahindrapduram B, Thompson AP, Thomson S, Tryfon A, Tsiantis J, Van Engeland H, Vincent JB, Volkmar F, Wallace S, Wang K, Wang Z, Wassink TH, Wing K, Wittemeyer K, Wood S, Yaspan BL, Zurawiecki D, Zwaigenbaum L, Betancur C, Buxbaum JD, Cantor RM, Cook EH, Coon H, Cuccaro ML, Gallagher L, Geschwind DH, Gill M, Haines JL, Miller J, Monaco AP, Nurnberger JI Jr, Paterson AD, Pericak-Vance MA, Schellenberg GD, Scherer SW, Sutcliffe JS, Szatmari P, Vicente AM, Vieland VJ, Wijsman EM, Devlin B, Ennis S, Hallmayer J. A genome-wide scan for common alleles affecting risk for autism. Hum Mol Genet. 2010 Oct 15;19(20):4072-82. [Epub 2010 Jul 27] [PMID: 20663923]

5: Jefferson A, Colella S, Moralli D, Wilson N, Yusuf M, Gimelli G, Ragoussis J, Volpi EV. Altered intra-nuclear organisation of heterochromatin and genes in ICF syndrome. PLoS One. 2010 Jun 29;5(6):e11364. [PMID: 20613881]

6: McCormick R, Buffa FM, Ragoussis J, Harris AL. The Role of Hypoxia Regulated microRNAs in Cancer. Curr Top Microbiol Immunol. 2010;810:47-70. [PMID: 20549470]

7: Pinto D, Pagnamenta AT, Klei L, Anney R, Merico D, Regan R, Conroy J,Magalhaes TR, Correia C, Abrahams BS, Almeida J, Bacchelli E, Bader GD, BaileyAJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bolte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Bryson SE, Carson AR, Casallo G, Casey J, Chung BH, Cochrane L, Corsello C, Crawford EL, Crossett A, Cytrynbaum C, Dawson G, de Jonge M, Delorme R, Drmic I, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Fombonne E, Freitag CM, Gilbert J, Gillberg C, Glessner JT, Goldberg J, Green A, Green J, Guter SJ, Hakonarson H, Heron EA, Hill M, Holt R, Howe JL, Hughes G, Hus V, Igliozzi R, Kim C, Klauck SM, Kolevzon A, Korvatska O, Kustanovich V, Lajonchere CM, Lamb JA, Laskawiec M, Leboyer M, Le Couteur A, Leventhal BL, Lionel AC, Liu XQ, Lord C, Lotspeich L, Lund SC, Maestrini E, Mahoney W, Mantoulan C, Marshall CR, McConachie H, McDougle CJ, McGrath J, McMahon WM, Merikangas A, Migita O, Minshew NJ, Mirza GK, Munson J, Nelson SF, Noakes C, Noor A, Nygren G, Oliveira G, Papanikolaou K, Parr JR, Parrini B, Paton T, Pickles A, Pilorge M, Piven J, Ponting CP, Posey DJ, Poustka A, Poustka F, Prasad A, Ragoussis J, Renshaw K, Rickaby J, Roberts W, Roeder K, Roge B, Rutter ML, Bierut LJ, Rice JP, Salt J, Sansom K, Sato D, Segurado R, Sequeira AF, Senman L, Shah N, Sheffield VC, Soorya L, Sousa I, Stein O, Sykes N, Stoppioni V, Strawbridge C, Tancredi R, Tansey K, Thiruvahindrapduram B, Thompson AP, Thomson S, Tryfon A, Tsiantis J, Van Engeland H, Vincent JB, Volkmar F, Wallace S, Wang K, Wang Z, Wassink TH, Webber C, Weksberg R, Wing K, Wittemeyer K, Wood S, Wu J, Yaspan BL, Zurawiecki D, Zwaigenbaum L, Buxbaum JD, Cantor RM, Cook EH, Coon H, Cuccaro ML, Devlin B, Ennis S, Gallagher L, Geschwind DH, Gill M, Haines JL, Hallmayer J, Miller J, Monaco AP, Nurnberger Jr JI, Paterson AD, Pericak-Vance MA, Schellenberg GD, Szatmari P, Vicente AM, Vieland VJ, Wijsman EM, Scherer SW, Sutcliffe JS, Betancur C. Functional impact of global rare copy number variation in autism spectrum disorders. Nature. 2010 Jul 15;466(7304):368-72. [Epub 2010 Jun 9] [PMID: 20531469]

8: Gee HE, Camps C, Buffa FM, Patiar S, Winter SC, Betts G, Homer J, Corbridge R, Cox G, West CM, Ragoussis J, Harris AL. hsa-mir-210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer. Cancer. 2010 May 1;116(9):2148-58. [PMID: 20187102]

9: Rzymski T, Milani M, Pike L, Buffa F, Mellor HR, Winchester L, Pires I,Hammond E, Ragoussis I, Harris AL. Regulation of autophagy by ATF4 in response to severe hypoxia. Oncogene. 2010  Aug 5;29(31):4424-35. [Epub 2010 May 31] [PMID:20514020]

10: De Santa F, Barozzi I, Mietton F, Ghisletti S, Polletti S, Tusi BK, Muller H, Ragoussis J, Wei CL, Natoli G. A large fraction of extragenic RNA pol II transcription sites overlap enhancers. PLoS Biol. 2010 May 11;8(5):e1000384. [PMID: 20485488]

11: Grzmil M, Rzymski T, Milani M, Harris AL, Capper RG, Saunders NJ, Salhan A, Ragoussis J, Norbury CJ. An oncogenic role of eIF3e/INT6 in human breast cancer. Oncogene. 2010 Jul 15;29(28):4080-9. [Epub 2010 May 10] [PMID: 20453879]

12: Favaro E, Ramachandran A, McCormick R, Gee H, Blancher C, Crosby M, Devlin C, Blick C, Buffa F, Li JL, Vojnovic B, Pires das Neves R, Glazer P, Iborra F, Ivan M, Ragoussis J, Harris AL. MicroRNA-210 regulates mitochondrial free radical response to hypoxia and krebs cycle in cancer cells by targeting iron sulphur cluster protein ISCU. PLoS One. 2010 Apr 26;5(4):e10345. [PMID: 20436681]

13: Ghisletti S, Barozzi I, Mietton F, Polletti S, De Santa F, Venturini E, Gregory L, Lonie L, Chew A, Wei CL, Ragoussis J, Natoli G. Identification and characterization of enhancers controlling the inflammatory gene expression program in macrophages. Immunity. 2010 Mar 26;32(3):317-28. [Epub 2010 Mar 4] [PMID: 20206554]

14: Butler HT, Warden DR, Hogervorst E, Ragoussis J, Smith AD, Lehmann DJ. Association of the aromatase gene with Alzheimer's disease in women. Neurosci Lett. 2010 Jan 14;468(3):202-6. [Epub 2009 Oct 30] [PMID: 19879925]

 

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Funding Sources

  1. INTEGER FP7 ITN Programme 241,000 Euro (2008-2012)
  2. MODEL-IN: Genomic determinants of inflamation FP7 Consortium (2008-2011) 349,210 Euros
  3. I. Udalova and J. Ragoussis:Systematic quantitative analysis of NFkb co-activators. MRC project grant 2008-2010 ; £207,900 to JR. 5% of time
  4. J. Ragoussis: Micro2DNA: EU FP6 Strep grant ( Feb 2006-2009): Microarray development work package 247,438 Euro 10% of time
  5. J. Ragoussis: EpigenChlamydia: EU FP6 (Dec 2006-2009) Coordination Action: Genotyping and QC work package 111,086 Euro 10% of time
  6. Co-applicant: Microarray-based discovery of plant growth regulatory genes (PI Prof. Nicholas Harberd BBSRC grant, 2008-20011 (£68,625 directly allocated to WTCHG) 5% of time
  7. Co-applicant: Wellcome Trust Prize Four Year PhD Studentships in Molecular Medicine 2008-13
  8. Co-applicant:Novel approaches for the genetic diagnosis of eye developmental disorders (co-applicant with Nichola Ragge, Birth Defects Foundation grant, 2008-9, £40,000 to WTCHG
  9. FP6 DC-THERA consortium member 2009-2010: £100,000

Also:

  1. Investigator in MalariaGen (D. Kwiatkowski),
  2. Collaborator-KAUST GRP programme grant: Crop domestication in the genome-biology era (N. Harberd) 2008-2013. Responsible for the application of genomic technologies.

Research Area(s)

Genomics

Keywords

SNP Genotyping, high-throughput sequencing, mutation detection, microarray and transcription factors