James is a Lecturer in Cell Biology in the Department of Biological Science (Faculty of Science and Engineering). His Oncobiology & Targeted Treatments Group investigates acetylation dependent DNA damage responses, develops novel histone acetyltransferase inhibitors, and breast cancer biomarker identification.
Maintaining genome stability following DNA double strand breaks (DSB) involves a complex signalling cascade, regulated by key acetylation events. DSB are among the most damaging genotoxic stress, with sustained DNA damage leading to tumourigenesis. The family of Histone (or lysine) acetyltransferases (KAT) regulate acetylation, and within the KAT family Tip60 is an essential protein controlling the DSB response.
Worldwide, approximately 1/8 women will develop breast cancer in their lifetime, with a >20% mortality rate. Treatments and survival rates are subtype specific, and new, targeted treatment options are needed. Our translational work focuses on validating our small molecule inhibitors (KATi) targeting Tip60. Investigating and validating new breast cancer biomarkers, allows improved patient stratification and enriched understanding of tumour (and subtype specific), molecular changes.
His fundamental research, using KATi, is revealing the molecular mechanisms (underpinning breast cancer) regulated by acetyltransferases (Tip60 centric) in genome protection and epigenetic modifications. Understanding the molecular roles of Tip60 will reveal fundamental molecular events regulating DSB responses.
Gao C, Bourke E, Scobie M, Famme MA, Koolmeister T, Helleday T, Eriksson LA, Lowndes NF, Brown JA. Rational design and validation of a Tip60 histone acetyltransferase inhibitor. Scientific Reports. 2014. 20;4:5372. https://doi.org/10.1038/srep05372 PMID: 24947938.
McGuire A, Casey MC, Shalaby A, Holian E, Kalinina O, Curran C, Webber M, Callagy G, Bourke E, Kerin MJ. Brown JA. Quantifying Tip60 protein level stratifies breast cancer. Scientific Reports. 2019. 9:3819. https://DOI:10.1038/s41598-019-40221-5
Casey MC, Prakash A, Holian E, McGuire A, Kalinina O, Shalaby A, Curran C, Webber M, Callagy G, Bourke E, Kerin MJ, Brown JA. Ago2 protein levels predict breast cancer survival, subtype and stage. BMC Cancer. 19:712. https://doi.org/10.1186/s12885-019-5884-x.
Brown JAL, Bourke E, Eriksson LA, Kerin MJ. Targeting cancer using KAT inhibitors to mimic lethal knockouts. Biochemical Society Transactions. 2016. Aug 15;44(4):979-86. doi: 10.1042/BST20160081. PMID: 27528742.
McGuire A*, Brown JAL*, Lowery A, Malone C, McLaughlin R, Kerin MJ. Effects of age on the detection and management of breast cancer. Cancers (Basel). 2015. 7(2), 908-929; Special Issue "Cancers and Aging" https://doi:10.3390/cancers7020815. PMID: 26010605.