Mark is Chief Scientist, Oncology within AstraZeneca's IMED Biotech Unit in Cambridge, UK, heading up the DNA Damage Response (DDR) biology area.
This involves leading the strategy to identify and develop inhibitors of DDR to generate new medicines for cancer patients. The current portfolio includes one approved product, two agents in clinical trials and an ATM inhibitor due to enter the clinic in 2015. Mark is also lead scientist for AstraZeneca’s recently approved PARP inhibitor and AZD1775, a WEE1 inhibitor in Phase II. A key component of the DDR strategy was the in-licensing of the WEE1 inhibitor AZD1775 from Merck in late 2013.
After going to Bristol University in 1983 to study Microbiology, Mark gained a PhD in Molecular Genetics in the Biochemistry department before moving to Singapore as a postdoctoral fellow at the Institute of Molecular and Cell Biology, where he worked on the transcriptional regulation of human papillomavirus oncogenes and their association with cervical cancer. In 1999, Mark 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, and at the time of his move to AstraZeneca in 2010 was Chief Scientist.
DNA repair represents an Achilles’ heel of cancer that AstraZeneca’s leading portfolio of DDR agents can exploit for the benefit of patients.
MOLECULAR CELL DDR PAPER
Authored Molecular Cell Review paper Targeting the DNA Damage Response in Cancer, highlighting different concepts behind targeting DNA Damage Response (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
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
2011 Cozzarelli Prize
UK DTI Link Award
UK DTI SMART Award
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