Dr James Brown

Lecturer in Discipline of Surgery
School of Medicine, Lambe Institute for Translational Research

Research interests

  • Characterising the molecular role of Histone acetyltransferases in breast cancer
  • Developing novel histone acetyltransferase inhibitors for cancer treatment
  • Identifying and characterising breast cancer biomarkers

Research overview

Maintaining genome stability following DNA double strand breaks (DSB) involves a complex signaling cascade, regulated by key acetylation events. DSB are among the most damaging stress cells encounter, 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.

Our laboratory, at the Lambe Institute for Translational Research, encompasses both basic and translational research, using a breast cancer model. Worldwide, approximately 1/8 women will develop breast cancer in their lifetime, with a >20% mortality rate. The 4 clinically relevant subtypes are categorised using established biomarkers. Treatments and survival rates are subtype specific, and new, targeted treatment options are needed.

Our translational work is focused on pre-clinical and early clinical validation of Tip60 targeting small molecule inhibitors (KATi) we developed. Additionally, our work investigates new breast cancer biomarkers, for improved patient stratification and improved understand of in vivo, subtype specific, molecular changes.

Our basic 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, and our KATi are potential novel targeted therapeutics for breast cancer.

 

Selected publications

  • 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. Sci Rep. 20;4:5372 (2014). PMID: 24947938.
  • Brown JAL, Bourke E, Eriksson LA, Kerin MJ. Targeting cancer using KAT inhibitors to mimic lethal knockouts. Biochemical Society Transactions. Aug 15;44(4):979-86 (2016). PMID: 27528742.