Replication fork collapse through ATR inhibition as a cancer treatment
Dr. Brown studies the mechanisms that safeguard genome integrity during replication and investigates how defects in these processes impact tissue homoeostasis, cancer risk, and cancer treatment. His work has focused on three specific areas: 1) cell extrinsic mechanisms that limit the accumulation replication stress-induced DNA damage in tissues[1,2], 2) the promise of ATR-CHK1 pathway inhibitors as cancer treatments[1-4], and 3) the role of ATR in preventing replication fork collapse and genomic instability[5,6]. In regards to the third research area, Dr. Brown’s laboratory has studied on how layered networks of checkpoint and repair genes cooperate to suppress double strand breaks in S phase and has identified novel synthetic lethal interactions for potential use in cancer treatment. His laboratory’s most recent study in this area implicates the AURKA-PLK1 pathway and the SUMO-targeted Ubiquitin ligase RNF4 as driving forces in replication fork collapse when ATR function is compromised6. This work and Dr. Brown’s demonstration that ATR-CHK1 inhibition is synthetically lethal with oncogene expression[3,4] have remarkable potential for clinical application, particularly in terms of the breadth of cancers in which ATR and CHK1 inhibitors may be applied.
Date: 24 July 2015, 12:15 (Friday, 13th week, Trinity 2015)
Venue: Old Road Campus Research Building, Headington OX3 7DQ
Venue Details: Ludwig Seminar Room, Lower Ground Floor
Speaker: Dr Eric Brown (University of Pennsylvania)
Organising department: Department of Oncology
Organiser: Linda Nemerofksy-Birks (University of Oxford)
Organiser contact email address:
Hosts: Vincenzo D'Angiolella (University of Oxford), Madalena Tarsounas (University of Oxford )
Part of: Department of Oncology
Booking required?: Not required
Audience: Members of the University only
Editor: Amanda Chapman