个人简介

B.Sc. (Bachelor of Science) Ph.D. (Doctor of Philosophy)

研究领域

Molecular Biology and Disease Cell Signalling and Structure

The Lees-Miller lab studies how mammalian cells detect and repair DNA double strand breaks (DSBs). DSBs are caused by exogenous DNA damaging agents such as ionizing radiation (IR), reactive oxygen species (ROS) and topoisomerase poisons. They also occur as a consequence of natural cellular processes such as oxidative metabolism and V(D)J recombination. Cells that are unable to detect and/or repair DSBs are highly radiosensitive and exhibit genomic instability. One of the major projects in the Lees-Miller lab is to understand the mechanism of Non Homologous End Joining (NHEJ), which is the major pathway for the repair of IR-induced DSBs in human cells. Her recent work has focused on the role of the DNA-dependent protein kinase (DNA-PK) in NHEJ and other cellular processes. The lab is also studying how small molecule inhibitors of poly ADP ribose polymerase (PARP) can be used to selectively target human tumours with deficiencies in DNA damage response proteins such as ATM (ataxia telangiectasia mutated) and more recently has embarked on a new research project with Dr Corinne Doll in the Tom Baker Cancer centre to investigate the effects of mutations in the phosphatidyl inositol 3 kinase (PI3K) pathway on cellular response to IR and other DNA damaging agents.

近期论文

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Phosphorylation of SAF-A/hnRNP-U Serine 59 by Polo-Like Kinase 1 Is Required for Mitosis. Douglas P, Ye R, Morrice N, Britton S, Trinkle-Mulcahy L, Lees-Miller SP. Mol Cell Biol. 2015 Aug;35(15):2699-713. Low ATM protein expression in malignant tumor as well as cancer-associated stroma are independent prognostic factors in a retrospective study of early-stage hormone-negative breast cancer. Feng X, Li H, Dean M, Wilson HE, Kornaga E, Enwere EK, Tang P, Paterson A, Lees-Miller SP, Magliocco AM, Bebb G. Breast Cancer Res. 2015 May 3;17:65. The DNA-dependent protein kinase: A multifunctional protein kinase with roles in DNA double strand break repair and mitosis. Jette N, Lees-Miller SP. Prog Biophys Mol Biol. 2015 Mar;117(2-3):194-205. Polo-like kinase 1 (PLK1) and protein phosphatase 6 (PP6) regulate DNA-dependent protein kinase catalytic subunit (DNA-PKcs) phosphorylation in mitosis. Douglas P, Ye R, Trinkle-Mulcahy L, Neal JA, De Wever V, Morrice NA, Meek K, Lees-Miller SP. Biosci Rep. 2014 May 20 [Epub ahead of print].Rey M, Yang M, Burns KM, Yu Y, Lees-Miller SP, Schriemer DC. (2013) Nepenthesin from monkey cups for Hydrogen/Deuterium Exchange Mass Spectrometry, Molecular and Cellular Proteomics, 12(2):464-72. Low ATM protein expression and depletion of p53 correlates with olaparib sensitivity in gastric cancer cell lines. Kubota E, Williamson CT, Ye R, Elegbede A, Petersen L, Lees-Miller SP, Beb DG. Cell Cycle 2014 May 19:13(13). [Epub ahead of print]. PIK3CA mutational status and overall survival in patients with cervical cancer treated with radical chemoradiotherapy, McIntyre JB, Wu JS, Craighead PS, Phan T, Köbel M, Lees-Miller SP, Ghatage P, Magliocco AM, Doll CM. (2013)Gynecologic Oncology, 128(3):409-14. Functional intersection of ATM and DNA-dependent protein kinase catalytic subunit in coding end joining during V(D)J recombination. Lee B-S, Gapud EJ, Zhang S, Dorsett Y, Bredmeyer A, George R, Callen E, Daniel JA, Osipovich O, Oltz EM, Bassing CH, Nussenzweig A, Lees-Miller S, Hammel M, Chen BPC and Sleckman BP. (2013)Molec. Cell Biol., 33(18):3568-3579. Telomerase contributes to fludarabine resistance in primary human leukemic lymphocytes. Shawi M, Chu TW, Martinez-Marignac V, Yu Y, Gryaznov SM, Johnston JB, Lees-Miller SP, Assouline SE, Autexier C, Aloyz R. (2013) PLoS One. 2013 Jul 29;8(7):e70428. doi: 10.1371/journal.pone.0070428. PMID:23922990 New roles for XRCC4 and XLF in DNA end alignment facilitating DNA double strand break repair. Mahaney BL, Hammel M, Meek K, Lees-Miller SP. (2013) Biochemistry & Cell Biology, 91(1):31-41. doi: 10.1139/bcb-2012-0058 (invited review) Targeting Protein for Xenopus kinesin like protein 2 (TPX2) regulates gamma H2AX levels upon ionizing radiation. Neymeyer, G. Helfricht, A, Shim SY, Le HT, Lundin C, Belzil C, Chansard M, Yu Y, Lees-Miller SP, Gruss O, van Attikum H, Helleday T and Nguyen MD. (2012) J. Biol. Chem, 287(50):42206-22. The Significance of Tumoral ERCC1 Status in Patients with Locally Advanced Cervical Cancer Treated with Chemoradiotherapy: A Multicenter Clinicopathologic Analysis. Doll CM, Aquino-Parsons C, Pintilie M, Klimowicz AC, Petrillo SK, Milosevic M, Craighead PS, Clarke B, Lees-Miller SP, Fyles AW, and Magliocco AM. (2012) International Journal of Radiation Oncology, Biology, Physics, 85(3):721-7. Enhanced cytotoxicity of PARP inhibition in Mantle Cell Lymphoma harboring mutations in both ATM and p53. Williamson CT, Kubota E, Hamill JD, Klimowicz A, Ye R, Muzik H, Dean M,Tu LR, Gilley D, Magliocco AM, McKay BC, Bebb DG, and Lees-Miller SP. (2012) EMBO