UQDI Seminar - Dr Anthony Cesare, Children’s Medical Research Institute, Sydney

Impediments that slow the rate of DNA replication are collectively referred to as “replication stress”. Replication stress is the main driver of genome instability in oncogenesis and is recognised as a hallmark of cancer. Much of the oncogenic effect of DNA replication stress comes through inappropriate chromosome segregation errors during mitosis. Within the clinic, pharmacological induction of DNA replication is an established frontline approach for chemotherapeutic cancer intervention. Lethal replication stress has previously been associated with “mitotic catastrophe”, a broad descriptor encompassing the complex and poorly understood mechanisms connecting genomic insult to mitotic disruption and cell death. Despite the clinical relevance of mitotic catastrophe and lethal DNA replication stress, no clear mechanisms of replication stress-induced cell death are established.

Dr. Anthony (Tony) Cesare is the Leader of the CMRI Genome Integrity Group. He obtained his BSc from Willamette University (Salem, Oregon, USA) and his PhD from the University of North Carolina at Chapel Hill (USA) before training as a USA National Science Foundation International Research Fellow with Roger Reddel at CMRI and a USA National Institutes of Health Ruth L. Kirschstein NRSA Fellow with Jan Karlseder at the Salk Institute (La Jolla, California, USA). He returned to Sydney in June 2013 to establish his own research group at CMRI with the assistance of a Cancer Institute NSW Future Research Leader Award.

Dr. Cesare’s research explores how molecular changes at the chromosome ends, or “telomeres”, during cellular ageing functions to prevent cancer and how these processes are affected during carcinogenesis. He discovered that during the ageing process molecular changes at telomeres result in a unique DNA damage response that causes protective growth arrest. This research also elucidated why pre-cancerous and cancerous cells are able to bypass this protective growth arrest, which can often result in genome instability and oncogenic transformation. His group’s current efforts are focused on understanding the unique signaling mechanisms activated by telomeres when they lose their protective functions in aged or cancerous cells and using this as a model to understand cellular mechanisms that have evolved to protect the genome. He is also developing novel methods to visualize dynamic telomere functions during normal cellular growth and in cancer cells.