个人简介
I am a Senior Lecturer in Cancer Biology, Chairman and Group Leader at the North West Cancer Research Institute, and holder of a prestigious CRUK Career Establishment Award.
CRUK Career Establishment Award: Analysis of MRN-dependent and -independent topoisomerase removal mechanisms: implications for resistance against camptothecin and etoposide derivatives
Knowledge Economy Skills Scholarship (KESS) PhD studentship (together with Dr. Simon Gollins; matched funding from BCUHB) : Identification of genetic markers that predict cancer patient survival following novel rectal cancer chemoradiation including concurrent irinotecan
Tenovus PhD studentship: The role of nucleotide excision repair in providing resistance to the nucleoside analogues Gemcitabine and Cytarabine.
Ser Cymru National Research Network PhD studentship (together with Dr. Simon Gollins; matched funding from BCUHB and BU): Role of DNA repair in resisting treatment with Gemcitabine and other nucleoside analogues
Knowledge Economy Skills Scholarship (KESS) PhD studentship (with Prof. Nick Stuart and Dr. Oliver Fleck; matched funding from BCUHB): Identification and evaluation of mutations in DNA repair genes as prognostic and/or predictive markers for cancer therapy
Cancer Research Wales PhD studentship (together with Prof. Simon Reed) : Genome-wide analysis of topoisomerase removal after camptothecin treatment in the context of replication and transcription.
Previous funding
North West Cancer Research Project Grant: Identification and analysis of DNA repair mechanisms that contribute to resistance against nucleoside analogues
North West Cancer Research Project Grant: The role of the MRE11 nuclease activity in resistance to topoisomerase poisons and nucleoside analogues
Cancer Research UK Project Grant: Analysis of camptothecin resistance mechanisms in Schizosaccharomyces pombe
I have successfully completed my Postgraduate Certificate in Teaching and Learning in Higher Education (PGCertHE) and am a Fellow of the Higher Education Academy (FHEA).
I am currently the module organiser of and lecture on BSX2019 “Molecular Biology and Biochemistry”. I also lecture on BSM-4023 “Genomes and Molecular Genetics” and run part of the practical course BSP-2062 “Molecular and Biochemistry Pracs”
I have co-authored an article on meiosis, aimed at undergraduates, part of the Wiley “Encyclopedia of Life Sciences” (http://www.els.net)
I have successfully supervised more than 15 MSc students, 2 PhD students, more than 10 undergraduate project students, and am currently supervising 4 PhD students.
I give regular guest Lectures at the University of Copenhagen and have been a regular instructor on the international EMBO course “Molecular Genetics with Fission yeast Schizosaccharomyces pombe”
I have been external PhD examiner at the Universities of Vienna, Copenhagen, Oxford, Cardiff and Lancaster
Committees:
SBS Board of Studies
Groups:
SBS Academic Staff
SBS Teaching Staff
研究领域
My current research focusses around the role that DNA repair mechanisms play in resisting treatment with clinically important DNA damaging cancer drugs. Topoisomerase inhibitors (e.g. Irinitecan and Etoposide) and nucleoside analogues (e.g. Gemcitabine and Ara-C) have been used for decades in the clinic, but little is known about DNA repair pathways that resist treatment with these important cancer drugs. To improve efficacy and tailor the choice of drug to specific genetic defects in tumours (personalised medicine), we need to understand which pathways resist treatment. An MRE11 mutation, found in the majority of colorectal cancers with microsatellite instability, results in loss of nuclease activity. We have previously shown that Mre11 nuclease activity contributes to resistance against topoisomerase poisons (e.g. Irinotecan) by removing covalently bound topoisomerases from DNA. We recently obtained evidence that this activity is also able to remove a replication-blocking nucleoside analogue from DNA and thus contributes to resistance. We are currently researching the role of various DNA repair pathways in resisting treatment with topoisomerase inhibitors and nucleoside analogues, with an aim to provide a rationale for personalised treatment of cancer patients, and in the long term, to identify potential targets suitable for small molecule inhibitors that target (redundant) resistance pathways.
近期论文
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Zech J, Godfrey EL, Masai H, Hartsuiker E, Dalgaard JZ. (2015) The DNA-Binding Domain of S. pombe Mrc1 (Claspin) Acts to Enhance Stalling at Replication Barriers. PLoS One 10(7)
Zhou Z, Humphryes N, van Eijk P, Waters R, Yu S, Kraehenbuehl R, Hartsuiker E, Reed SH. (2015) UV induced ubiquitination of the yeast Rad4-Rad23 complex promotes survival by regulating cellular dNTP pools. Nucleic Acids Res. 43(15):7360-70
Hartsuiker E. (2011) Detection of covalent DNA-bound Spo11 and topoisomerase complexes. Methods Mol Biol. 745:65-77
Nakamura K., Kogame T., Oshiumi H., Shinohara A., Sumitomo Y., Agama K., Pommier Y., Tsutsui K.M., Tsutsui K., Hartsuiker E., Ogi T., Takeda S., and Taniguchi Y. (2010) Collaborative action of Brca1 and CtIP in elimination of covalent modifications from double-strand breaks to facilitate subsequent break repair. PLoS Genet. 6:e1000828 (8.5)
Durand-Dubief M., Persson J., Norman U., Hartsuiker E. and Ekwall K. (2010) Topoisomerase I regulates open chromatin and controls gene expression in vivo. EMBO. J. 29:2126-34 (9.8)
Lloyd J., Chapman J.R., Clapperton J.A., Haire L.F., Hartsuiker E., Li J., Carr A.M., Jackson S.P., Smerdon S.J. (2009) A supramodular FHA/BRCT-repeat architecture mediates Nbs1 adaptor function in response to DNA damage. Cell. 139:100-11 (32.0)
Hartsuiker E.*, Neale M and Carr A.M. (2009) Distinct requirements for the Rad32Mre11 nuclease and Ctp1CtIP in the removal of covalently bound topoisomerase I and II from DNA. Molecular Cell 33:117-23. (15.3)
*corresponding author
Hartsuiker E.*, Mizuno K., Molnar M., Kohli J., Ohta K. and Carr A.M. (2009) Ctp1CtIP and the Rad32Mre11 nuclease activity are required for Rec12Spo11 removal, but this activity is dispensable for other MRN-dependent meiotic functions. Mol. Cell. Biol. 29:1671-81.(5.4)
*corresponding author
Deshpande G., Hayles J., Hoe K.L., Kim D.U., Park H.O. and Hartsuiker E. (2009) Screening a genome wide S. pombe deletion library identifies novel genes and pathways involved in genome stability maintenance. DNA repair 8:672-679. (4.3)
Kohli J. and Hartsuiker E. (2008) Meiosis. In: Encyclopedia of life sciences. John Wiley & Sons, Ltd: Chichester.
El-Khamisy S.F., Hartsuiker E. and Caldecott K.W. (2007) TDP1 facilitates repair of ionizing radiation-induced DNA single-strand breaks. DNA Repair 6:1485-95. (4.3)
Raji H. and Hartsuiker E. (2006) Double-strand break repair and homologous recombination in Schizosaccharomyces pombe. Yeast 23:963-76. (2.0)
Baur M., Hartsuiker E., Lehmann E., Ludin K., Munz P. and Kohli J. (2005) The meiotic recombination hot spot ura4A in Schizosaccharomyces pombe. Genetics 169:551-61. (4.4)
Yamada T., Mizuno K., Hirota K., Kon N., Wahls W.P., Hartsuiker E., Murofushi H., Shibata T. and Ohta K. (2004) Roles of histone acetylation and chromatin remodelling factor in a meiotic recombination hotspot. EMBO J. 23:1792-803. (9.8)
Werler P.J., Hartsuiker E. and Carr A.M. (2003) A simple Cre-loxP method for chromosomal N-terminal tagging of essential and non-essential Schizosaccharomyces pombe genes. Gene 304:133-41. (2.2)
Marchetti M.A., Kumar S., Hartsuiker E., Maftahi M., Carr A.M., Freyer A.F. , Burhans W.C. and Huberman J.A. (2002) A single unbranched S-phase DNA damage and replication fork blockage checkpoint pathway. Proc. Natl. Acad. Sci. USA. 99:7472-7 (9.7)
Farah J.A., Hartsuiker E., Mizuno K., Ohta K. and Smith G.R. (2002) A 160 bp palindrome is a Rad50.Rad32-dependent mitotic recombination hotspot in Schizosaccharomyces pombe. Genetics 161:461-468 (4.4)
Hartsuiker E., Vaessen E., Carr A.M. and Kohli J. (2001) Fission yeast Rad50 stimulates sister chromatid recombination and links cohesion with repair. EMBO J. 20:6660-6671 (9.8)
Manolis K.G., Nimmo E.R., Hartsuiker E., Carr A.M., Jeggo P.A. and Allshire R.C.
(2001) Novel Functional requirements for non-homologous end joining in Schizosaccharomyces pombe. EMBO J. 20:210-221 (9.8)
Rudolph C., Kunz C., Parisi S., Lehmann E., Hartsuiker E., Fartmann B., Kramer W., Kohli J. and Fleck O. (1999). The msh2 gene of Schizosaccharomyces pombe is involved in mismatch repair, mating type switching and meiotic chromosome organization. Mol. Cell. Biol. 19: 241-250 (5.4)
Hartsuiker E., Bähler J. and Kohli J. (1998). The role of topoisomerase II in meiotic chromosome condensation and segregation in Schizosaccharomyces pombe. Mol. Biol. Cell. 9:2739-2750 (4.8)
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