Tony Kouzarides

Tony Kouzarides
Born (1958-01-17) 17 January 1958[1]
Fields Cancer
Chromatin
Transcription
Institutions University of Leeds
University of Cambridge
Gurdon Institute
New York University
Laboratory of Molecular Biology
Abcam
Alma mater University of Leeds (BSc)
University of Cambridge (PhD)
Thesis A molecular analysis of transformation by human cytomegalovirus (1985)
Doctoral advisor Tony Minson[2]
Doctoral students Jacqui Sutherland[3]
Helen Brown[4]
Juliet Reid [5]
Klaus Martin[6][7]
Eric Miska[8]
Philip Zegerman[9][10]
Wendy Bergers
Dan Wolf[11]
Graeme Cuthbert[12]
Karen Halls
Claire Pike[13]
Other notable students (postdocs)
Christian Hagemeier[14]
Didier Trouche[15]
Jonathan Milner[16][17]
Alex Brehm[18]
Catherine Le Chalony
Søren Neilson
Paul Lavender[19]
Francois Fuks[20]
Marian Martinez Balbas
Laurence Vandel[21]
Uta-Maria Bauer[22]
Guida Ruas
Emma Langley[23]
Sylvain Daujat[24]
Luke Hughes-Davies[25]
Robert Schneider[26]
Steve Sanders[27]
Susana Lopes
Chris Nelson[28]
Paul Hurd[29]
Sopie Deltour
David Lando[30]
Antonis Kirmizis[31][32]
Hatice Akarsu
Blerta Xhemalce[33]
Till Bartke[34]
Marc Schneider
Gonçalo Castelo-Branco[13]
Notable awards Heinrich Wieland Prize (2013)
Fellow of the Royal Society (2012)[35]
FMedSci (2001)[36]
Spouse Penny Hall[1]
Website
www.gurdon.cam.ac.uk/~kouzarideslab
royalsociety.org/people/tony-kouzarides

Tony Kouzarides, FMedSci,[36] FRS[35] (born 17 January 1958) is the deputy director of the Gurdon Institute,[37] a founding non-executive director of Abcam[38] and a Professor of Cancer Biology at the University of Cambridge.[39][40]

Education

Kouzarides was educated at the University of Leeds, graduating with a Bachelor of Science degree in Genetics in 1981.[1] He went on to complete his PhD at the University of Cambridge in 1985.[41]

Research

Following his PhD, Kouzarides did postdoctoral work at the Laboratory of Molecular Biology (LMB) on the cancer potential of cytomegalovirus.[42] and then on to New York University Medical Center. Here he examined the c-Fos leucine zipper dimerisation domain to elucidate its function. He got a job at the Gurdon Institute in Cambridge, where he has been since.[43]

Kouzarides is a leader in the field of chromatin modification[44] and its role in transcriptional control and cancer.[45][46] In 1996 he made a key discovery in finding that the transcriptional co-activator CBP[47] is a histone acetyltransferase.[48][49] He has since worked on identifying several new histone modifications, describing their functions in transcription and DNA repair and highlighting their mis-regulation in cancer. His demonstration that a histone acetylation pathway inhibitor can be used to treat MLL-leukaemias in has facilitated its use in clinical trials.[35]

Awards

Kouzarides was elected a member of the Academy of Medical Sciences (FMedSci) in 2001[36] a Fellow of the Royal Society (FRS) in 2012.[35] His nomination read:

"Tony Kouzarides is world leader in the field of chromatin modification and its roles in transcriptional control and cancer. His finding in 1996 that the transcriptional co-activator CBP is a histone acetyltransferase was one of the key discoveries that started the modern era of chromatin research. His subsequent work has identified several new histone modifications, described their functions in transcription and DNA repair and has highlighted their mis-regulation in cancer. His demonstration that a histone acetylation pathway inhibitor is an effective treatment for MLL-leukaemias in disease models has opened the way to its use in clinical trials."[35]

Kouzarides was also awarded the Sanofi-Cell Research Outstanding Paper Award of 2011[50] for his paper on Regulation of chromatin by histone modifications co-authored with Andrew Bannister.[51]

In 2013, he was awarded the Heinrich Wieland Prize for his pioneering "research on gene regulation and cancer"[52]

References

  1. 1 2 3 "KOUZARIDES, Prof. Tony". Who's Who 2013, A & C Black, an imprint of Bloomsbury Publishing plc, 2013; online edn, Oxford University Press. Retrieved 18 March 2015. (subscription required)
  2. ↑ Cranage, M. P.; Kouzarides, T.; Bankier, A. T.; Satchwell, S.; Weston, K.; Tomlinson, P.; Barrell, B.; Hart, H.; Bell, S. E.; Minson, A. C. (1986). "Identification of the human cytomegalovirus glycoprotein B gene and induction of neutralizing antibodies via its expression in recombinant vaccinia virus". The EMBO Journal 5 (11): 3057–3063. PMC 1167261. PMID 3024973.
  3. ↑ Sutherland, J. A.; Cook, A.; Bannister, A. J.; Kouzarides, T. (1992). "Conserved motifs in Fos and Jun define a new class of activation domain". Genes & Development 6 (9): 1810–1819. doi:10.1101/gad.6.9.1810. PMID 1516835.
  4. ↑ Brown, H. J.; Sutherland, J. A.; Cook, A.; Bannister, A. J.; Kouzarides, T. (1995). "An inhibitor domain in c-Fos regulates activation domains containing the HOB1 motif". The EMBO Journal 14 (1): 124–131. PMC 398059. PMID 7828584.
  5. ↑ Reid, J. L.; Bannister, A. J.; Zegerman, P.; Martínez-Balbás, M. A.; Kouzarides, T. (1998). "E1A directly binds and regulates the P/CAF acetyltransferase". The EMBO Journal 17 (15): 4469–4477. doi:10.1093/emboj/17.15.4469. PMC 1170778. PMID 9687513.
  6. ↑ Martin, K.; Trouche, D.; Hagemeier, C.; Sorensen, T. S.; La Thangue, N. B.; Kouzarides, T. (1995). "Stimulation of E2F1/DP1 transcriptional activity by MDM2 oncoprotein". Nature 375 (6533): 691–694. doi:10.1038/375691a0. PMID 7791903. horizontal tab character in |title= at position 58 (help)
  7. ↑ Martin, K.; Trouche, D.; Hagemeier, C.; Kouzarides, T. (1995). "Regulation of transcription by E2F1/DP1". Journal of cell science. Supplement 19: 91–94. doi:10.1242/jcs.1995.Supplement_19.13. PMID 8655653.
  8. ↑ Miska, E. A.; Langley, E.; Wolf, D.; Karlsson, C.; Pines, J.; Kouzarides, T. (2001). "Differential localization of HDAC4 orchestrates muscle differentiation". Nucleic Acids Research 29 (16): 3439–3447. doi:10.1093/nar/29.16.3439. PMC 55849. PMID 11504882.
  9. ↑ Zegerman, P.; Canas, B.; Pappin, D.; Kouzarides, T. (2002). "Histone H3 Lysine 4 Methylation Disrupts Binding of Nucleosome Remodeling and Deacetylase (NuRD) Repressor Complex". Journal of Biological Chemistry 277 (14): 11621–11624. doi:10.1074/jbc.C200045200. PMID 11850414.
  10. ↑ Zegerman, P.; Bannister, A. J.; Kouzarides, T. (2000). "The putative tumour suppressor Fus-2 is an N-acetyltransferase". Oncogene 19 (1): 161–163. doi:10.1038/sj.onc.1203234. PMID 10644992.
  11. ↑ Wolf, D.; Rodova, M.; Miska, E. A.; Calvet, J. P.; Kouzarides, T. (2002). "Acetylation of beta -Catenin by CREB-binding Protein (CBP)". Journal of Biological Chemistry 277 (28): 25562–25567. doi:10.1074/jbc.M201196200. PMID 11973335.
  12. ↑ Cuthbert, G. L.; Daujat, S.; Snowden, A. W.; Erdjument-Bromage, H.; Hagiwara, T.; Yamada, M.; Schneider, R.; Gregory, P. D.; Tempst, P.; Bannister, A. J.; Kouzarides, T. (2004). "Histone Deimination Antagonizes Arginine Methylation". Cell 118 (5): 545–553. doi:10.1016/j.cell.2004.08.020. PMID 15339660.
  13. 1 2 "Tony Kouzarides lab Alumni". Archived from the original on 2013-06-06.
  14. ↑ Hagemeier, C.; Bannister, A. J.; Cook, A.; Kouzarides, T. (1993). "The activation domain of transcription factor PU.1 binds the retinoblastoma (RB) protein and the transcription factor TFIID in vitro: RB shows sequence similarity to TFIID and TFIIB". Proceedings of the National Academy of Sciences of the United States of America 90 (4): 1580–1584. doi:10.1073/pnas.90.4.1580. PMC 45918. PMID 8434021.
  15. ↑ Trouche, D.; Kouzarides, T. (1996). "E2F1 and E1A(12S) have a homologous activation domain regulated by RB and CBP". Proceedings of the National Academy of Sciences of the United States of America 93 (4): 1439–1442. doi:10.1073/pnas.93.4.1439. PMC 39957. PMID 8643650.
  16. ↑ Milner, J.; Fuks, F. O.; Hughes-Davies, L.; Kouzarides, T. (2000). "The BRCA2 activation domain associates with and is phosphorylated by a cellular protein kinase". Oncogene 19 (38): 4441–4445. doi:10.1038/sj.onc.1203793. PMID 10980621.
  17. ↑ Milner, J.; Ponder, B.; Hughes-Davies, L.; Seltmann, M.; Kouzarides, T. (1997). "Transcriptional activation functions in BRCA2". Nature 386 (6627): 772–773. doi:10.1038/386772a0. PMID 9126734.
  18. ↑ Kouzarides, T.; Brehm, A.; Miska, E. A.; McCance, D. J.; Reid, J. L.; Bannister, A. J. (1998). "Retinoblastoma protein recruits histone deacetylase to repress transcription". Nature 391 (6667): 597–601. doi:10.1038/35404. PMID 9468139.
  19. ↑ Lavender, P.; Vandel, L.; Bannister, A. J.; Kouzarides, T. (1997). "The HMG-box transcription factor HBP1 is targeted by the pocket proteins and E1A". Oncogene 14 (22): 2721–2728. doi:10.1038/sj.onc.1201243. PMID 9178770.
  20. ↑ Fuks, F.; Hurd, P. J.; Deplus, R.; Kouzarides, T. (2003). "The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase". Nucleic Acids Research 31 (9): 2305–2312. doi:10.1093/nar/gkg332. PMC 154218. PMID 12711675.
  21. ↑ Vandel, L.; Kouzarides, T. (1999). "Residues phosphorylated by TFIIH are required for E2F-1 degradation during S-phase". The EMBO Journal 18 (15): 4280–4291. doi:10.1093/emboj/18.15.4280. PMC 1171504. PMID 10428966.
  22. ↑ Bauer, U. -M.; Daujat, S.; Nielsen, S. J.; Nightingale, K.; Kouzarides, T. (2001). "Methylation at arginine 17 of histone H3 is linked to gene activation". EMBO Reports 3 (1): 39–44. doi:10.1093/embo-reports/kvf013. PMC 1083932. PMID 11751582.
  23. ↑ Langley, E.; Pearson, M.; Faretta, M.; Bauer, U. M.; Frye, R. A.; Minucci, S.; Pelicci, P. G.; Kouzarides, T. (2002). "Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence". The EMBO Journal 21 (10): 2383–2396. doi:10.1093/emboj/21.10.2383. PMC 126010. PMID 12006491.
  24. ↑ Daujat, S.; Bauer, U. M.; Shah, V.; Turner, B.; Berger, S.; Kouzarides, T. (2002). "Crosstalk between CARM1 methylation and CBP acetylation on histone H3". Current Biology 12 (24): 2090–2097. doi:10.1016/s0960-9822(02)01387-8. PMID 12498683.
  25. ↑ Hughes-Davies, L.; Huntsman, D.; Ruas, M.; Fuks, F.; Bye, J.; Chin, S. F.; Milner, J.; Brown, L. A.; Hsu, F.; Gilks, B.; Nielsen, T.; Schulzer, M.; Chia, S.; Ragaz, J.; Cahn, A.; Linger, L.; Ozdag, H.; Cattaneo, E.; Jordanova, E. S.; Schuuring, E.; Yu, D. S.; Venkitaraman, A.; Ponder, B.; Doherty, A.; Aparicio, S.; Bentley, D.; Theillet, C.; Ponting, C. P.; Caldas, C.; Kouzarides, T. (2003). "EMSY links the BRCA2 pathway to sporadic breast and ovarian cancer". Cell 115 (5): 523–535. doi:10.1016/S0092-8674(03)00930-9. PMID 14651845.
  26. ↑ Schneider, R.; Bannister, A. J.; Weise, C.; Kouzarides, T. (2004). "Direct Binding of INHAT to H3 Tails Disrupted by Modifications". Journal of Biological Chemistry 279 (23): 23859–23862. doi:10.1074/jbc.C400151200. PMID 15100215.
  27. ↑ Sanders, S. L.; Portoso, M.; Mata, J.; Bähler, J. R.; Allshire, R. C.; Kouzarides, T. (2004). "Methylation of Histone H4 Lysine 20 Controls Recruitment of Crb2 to Sites of DNA Damage". Cell 119 (5): 603–614. doi:10.1016/j.cell.2004.11.009. PMID 15550243.
  28. ↑ Nelson, C. J.; Santos-Rosa, H.; Kouzarides, T. (2006). "Proline Isomerization of Histone H3 Regulates Lysine Methylation and Gene Expression". Cell 126 (5): 905–916. doi:10.1016/j.cell.2006.07.026. PMID 16959570.
  29. ↑ Hurd, P. J.; Bannister, A. J.; Halls, K.; Dawson, M. A.; Vermeulen, M.; Olsen, J. V.; Ismail, H.; Somers, J.; Mann, M.; Owen-Hughes, T.; Gout, I.; Kouzarides, T. (2009). "Phosphorylation of Histone H3 Thr-45 is Linked to Apoptosis". Journal of Biological Chemistry 284 (24): 16575–16583. doi:10.1074/jbc.M109.005421. PMC 2713519. PMID 19363025.
  30. ↑ Lando, D.; Balmer, J.; Laue, E. D.; Kouzarides, T. (2012). Kashanchi, Fatah, ed. "The S. Pombe Histone H2A Dioxygenase Ofd2 Regulates Gene Expression during Hypoxia". PLoS ONE 7 (1): e29765. doi:10.1371/journal.pone.0029765. PMC 3250473. PMID 22235339.
  31. ↑ Kirmizis, A.; Santos-Rosa, H.; Penkett, C. J.; Singer, M. A.; Green, R. D.; Kouzarides, T. (2009). "Distinct transcriptional outputs associated with mono- and dimethylated histone H3 arginine 2". Nature Structural & Molecular Biology 16 (4): 449–451. doi:10.1038/nsmb.1569. PMC 3350867. PMID 19270702.
  32. ↑ Kirmizis, A.; Santos-Rosa, H.; Penkett, C. J.; Singer, M. A.; Vermeulen, M.; Mann, M.; Bähler, J. R.; Green, R. D.; Kouzarides, T. (2007). "Arginine methylation at histone H3R2 controls deposition of H3K4 trimethylation". Nature 449 (7164): 928–932. doi:10.1038/nature06160. PMC 3350864. PMID 17898715.
  33. ↑ Xhemalce, B.; Robson, S. C.; Kouzarides, T. (2012). "Human RNA Methyltransferase BCDIN3D Regulates MicroRNA Processing". Cell 151 (2): 278–288. doi:10.1016/j.cell.2012.08.041. PMC 3640255. PMID 23063121.
  34. ↑ Bartke, T.; Vermeulen, M.; Xhemalce, B.; Robson, S. C.; Mann, M.; Kouzarides, T. (2010). "Nucleosome-Interacting Proteins Regulated by DNA and Histone Methylation". Cell 143 (3): 470–484. doi:10.1016/j.cell.2010.10.012. PMC 3640253. PMID 21029866.
  35. 1 2 3 4 5 "Professor Tony Kouzarides FMedSci FRS". Retrieved 24 April 2012.
  36. 1 2 3 "The Academy of Medical Sciences | Directory of Fellows". Archived from the original on 2013-06-06.
  37. ↑ "The Kouzarides Lab at the Gurdon Institute". Retrieved 24 April 2012.
  38. ↑ "Abcam board of directors". Retrieved 24 April 2012.
  39. ↑ "Professor Tony Kouzarides profile- Cambridge Cancer Centre". Archived from the original on 6 June 2013.
  40. ↑ Bannister, A. J.; Zegerman, P.; Partridge, J. F.; Miska, E. A.; Thomas, J. O.; Allshire, R. C.; Kouzarides, T. (2001). "Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain". Nature 410 (6824): 120–124. doi:10.1038/35065138. PMID 11242054.
  41. ↑ Kouzarides, Tony (1985). A molecular analysis of transformation by human cytomegalovirus (PhD thesis). University of Cambridge.
  42. ↑ Laursen, L. (2008). "Creativity and Persistence Overcome Failure: Tony Kouzarides tells the story of his early career as a comedy of errors". Science. doi:10.1126/science.caredit.a0800097.
  43. ↑ "About Tony Kouzarides". Retrieved 24 April 2012.
  44. ↑ Kouzarides, T. (2007). "Chromatin Modifications and Their Function". Cell 128 (4): 693–705. doi:10.1016/j.cell.2007.02.005. PMID 17320507.
  45. ↑ "Tony Kouzarides publications in Google Scholar". Retrieved 24 April 2012.
  46. ↑ http://www.ncbi.nlm.nih.gov/pubmed?term=kouzarides Kouzarides in PubMed
  47. ↑ Bannister, A. J.; Kouzarides, T. (1996). "The CBP co-activator is a histone acetyltransferase". Nature 384 (6610): 641–643. doi:10.1038/384641a0. PMID 8967953.
  48. ↑ Kouzarides, T.; Brehm, A.; Miska, E. A.; McCance, D. J.; Reid, J. L.; Bannister, A. J. (1998). "Retinoblastoma protein recruits histone deacetylase to repress transcription". Nature 391 (6667): 597–601. doi:10.1038/35404. PMID 9468139.
  49. ↑ Santos-Rosa, H.; Schneider, R.; Bannister, A. J.; Sherriff, J.; Bernstein, B. E.; Emre, N. C. T.; Schreiber, S. L.; Mellor, J.; Kouzarides, T. (2002). "Active genes are tri-methylated at K4 of histone H3". Nature 419 (6905): 407–411. doi:10.1038/nature01080. PMID 12353038.
  50. ↑ Li, D. (2012). "Sanofi-Cell Research Outstanding Paper Award of 2011". Cell Research 22 (11): 1511. doi:10.1038/cr.2012.153. PMC 3494390. PMID 23128785.
  51. ↑ Bannister, A. J.; Kouzarides, Tony (2011). "Regulation of chromatin by histone modifications". Cell Research 21 (3): 381–395. doi:10.1038/cr.2011.22. PMC 3193420. PMID 21321607.
  52. ↑ Heinrich Wieland Prize; accessed 18 March 2015. (German)
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