I head up the DNA Damage Response (DDR) biology area within AstraZeneca’s IMED Biotech Unit and am the science lead for the company’s broader DDR franchise.
I have devoted 20 years of my career to understanding the DNA damage response, with the aim of determining how this can be exploited to develop potential new treatments for cancer patients. Championing the growth of DDR within AstraZeneca, my current role involves informing the strategy to identify and develop inhibitors of DDR in oncology.
After going to Bristol University in 1983 to study Microbiology, I gained a PhD in Molecular Genetics before moving to Singapore as a postdoctoral fellow at the Institute of Molecular and Cell Biology, where I worked on the transcriptional regulation of human papillomavirus oncogenes and their association with cervical cancer.
In 1999, I returned to the UK to take up a position as one of the three science team leaders at KuDOS, a spin-out biotech company based on the work of Professor Steve Jackson at Cambridge University. Here, I researched the cellular network of pathways that minimise the daily impact of DNA damage in normal tissue but represent an Achille’s heel in cancers, where DDR dependencies can be targeted to generate new therapeutic treatments for cancer. It was at KuDOS in 2004 that I first started working on olaparib, a PARP inhibitor.
KuDOS was acquired by AstraZeneca at the end of 2005 and in 2010 I moved to AstraZeneca to head up the DDR biology area, one of the four key platforms in our oncology portfolio.
As well as being a named inventor on multiple patents, I have a strong publication record, many of which have come through close external collaborations, that include peer reviewed publications in Cell, Cancer Cell, Cancer Discovery, Molecular Cell, Nature Cell Biology, Journal of Clinical Oncology and the New England Journal of Medicine.
2011 Cozzarelli Prize
UK DTI Link Award
UK DTI SMART Award
MOLECULAR CELL DDR PAPER
Authored Molecular Cell Review paper, Targeting the DNA Damage Response in Cancer, highlighting different concepts behind targeting DDR and how this can provide significant opportunities for DDR-based therapies in the future
APPROVAL OF FIRST DDR MEDICINE
Oncology IMED Innovation and Achievement Award ‘Winner of the Winners’ 2015
Gordon Research Conference on Mammalian DNA Repair in Ventura, 2015 AACR Special Conference on DNA Repair in Montreal, 2016
Targeting the replication stress response in cancer
Targeting the replication stress response in cancer. Forment J & O’Connor M. Pharmacology & Therapeutics 2018: 188; 155-167
Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action
Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action O’Connor MJ. Science Translational Medicine 26 Oct 2016: Vol. 8, Issue 362, pp. 362ps17
Targeting the DNA Damage Response in Cancer
Targeting the DNA Damage Response in Cancer. O’Connor MJ. Mol Cell 2015: 60(4): 547-560
Inhibition of PARP in tumours from BRCA mutation carriers
Inhibition of Poly(ADP-Ribose) Polymerase in Tumors from BRCA Mutation Carriers. Fong PC1, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O'Connor MJ, Ashworth A, Carmichael J, Kaye SB, Schellens JH, de Bono JS. New Engl J Med 2009: 361(2):123-34.
Loss of 53BP1 causes PARP inhibitor resistance
Loss of 53BP1 causes PARP inhibitor resistance in BRCA1-mutated mouse mammary tumors. Jaspers JE1, Kersbergen A, Boon U, Sol W, van Deemter L, Zander SA, Drost R, Wientjens E, Ji J, Aly A, Doroshow JH, Cranston A, Martin NM, Lau A, O'Connor MJ, Ganesan S, Borst P, Jonkers J, Rottenberg S. Cancer Discovery 2013: 3(1): 68-81.
Mild hyperthermia sensitizes cancer cells to PARP inhibition
Mild hyperthermia inhibits homologous recombination, induces BRCA2 degradation, and sensitizes cancer cells to poly (ADP-ribose) polymerase-1 inhibition. Krawczyk PM, Eppink B, Essers J, Stap J, Rodermond H, Odijk H, Zelensky A, van Bree C, Stalpers LJ, Buist MR, Soullié T, Rens J, Verhagen HJ, O'Connor MJ, Franken NA, Ten Hagen TL, Kanaar R, Aten JA. Proc Natl Acad Sci U S A. 2011: 108(24):9851-6.
High sensitivity of BRCA1-deficient tumors to PARP inhibition
High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs. Rottenberg S1, Jaspers JE, Kersbergen A, van der Burg E, Nygren AO, Zander SA, Derksen PW, de Bruin M, Zevenhoven J, Lau A, Boulter R, Cranston A, O'Connor MJ, Martin NM, Borst P, Jonkers J.Proc Natl Acad Sci U S A. 2008: 105(44):17079-84.
hnRNP K: an HDM2 target
hnRNP K: an HDM2 target and transcriptional coactivator of p53 in response to DNA damage. Moumen A1, Masterson P, O'Connor MJ, Jackson SP. Cell 2005 16: 123(6):1065-78.
Suppression of HIV infection by ATM inhibitors
Suppression of HIV infection by a small molecule inhibitor of ATM kinase. Lau A1, Swinbank KM, Ahmed PS, Taylor DL, Jackson SP, Smith GC, O'Connor MJ. Nat Cell Biol. 2005 7(5):493-500
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