Tomas Goncalves

MSci, DPhil

Postdoctoral Researcher

Description of Research

Tomas Goncalves is a Postdoctoral researcher in the Department of Paediatrics working within the Weatherall Institute of Molecular Medicine. His research focuses on the role that telomeres play in the development of paediatric solid tumours.

Telomeres are the protective ends of chromosomes. After every cell division, telomeres shorten due to the end-replication problem. This continues until they reach a critically shortened state where they elicit DNA damage checkpoint activation, stopping further divisions. Therefore, for cancer cells to divide indefinitely, they must maintain the ends of their chromosomes through a telomere maintenance mechanism to prevent replicative senescence or apoptosis.

In about 90% of cancers, the enzyme telomerase, which replenishes telomeric DNA, is reactivated, permitting indefinite cell divisions. In the absence of telomerase activity, about 10-15% of tumours can gain a telomerase independent, alternative pathway to maintain their telomeres, termed the alternative lengthening of telomeres (ALT), which is dependent on homologous recombination. The ALT pathway is more common in certain cancers, mainly those of a mesenchymal origin, including some brain cancers and certain sarcomas, particularly osteosarcoma.

ALT activity appears to be unique to cancer cells. However, despite this novel feature of telomerase-independent telomere maintenance, effective drugs that selectively kill ALT-positive cancer cells have yet to be discovered. As many as yet untreatable childhood cancers extend their telomeres via ALT, a greater understanding of this pathway may provide much needed treatments for such cancers.