The Cancer Research Unit conducts trailblazing work on telomeres, which are important for senescence (aging) and all cancers.
Our main emphasis is on understanding how cancer cells continue to proliferate using the Alternative Lengthening of Telomeres (ALT) mechanism.
Better understanding of this mechanism will enable us to develop better treatments against ALT cancers, which are some of the most aggressive types, including glioblastoma brain tumours and osteosarcomas.
Focused, translational-oriented research is needed to advance these discoveries to the next stages, where they can be useful to patients, and that’s where we are right now. However, we also need basic, curiosity-driven research to continue if we are to make the truly great discoveries. CMRI’s culture has long been supportive of both types of research.”
Most of the work in the Cancer Research Unit (CRU) currently focuses on understanding telomeres and how these structures at the ends of chromosomes are maintained in cancer cells. Telomeres shorten each time a cell divides, and this acts as a countdown eventually telling cells to stop proliferating. Cancer cells are able to counteract the shortening process and continue to proliferate out of control. In order to keep growing, the cancer cells must activate the enzyme telomerase or the Alternative Lengthening of Telomeres (ALT) mechanism, either of which can counteract telomere shortening. The ALT mechanism was originally discovered by the CRU, and the team continues to focus on understanding how this mechanism works, and most importantly, how to inhibit it in order to treat cancer.
Director of CMRI, Co-Director of ProCan, and Head of the Cancer Research Unit
Project Manager, Cancer Research Unit
We are investigating many aspects of telomere chromatin structure and telomere biology, including telomere length trimming and telomeric DNA sequences. Our aim is to understand how ALT telomeres are structured and how they differ from telomeres in normal and telomerase-positive cells. This will help us to understand the ALT mechanism in more detail and provide information on possible targets for interfering with ALT activity in cancer cells.
The C-circle assay for detecting ALT activity, which was developed by Jeremy Henson in our laboratory, has enabled us to search for the genes that repress ALT in normal cells. We are also using this and other techniques to find the genes needed for ALT activity. These studies will enable us to find targets for the development of ALT-inhibiting therapeutic drugs to treat cancer.
We have developed a way to detect ALT activity in mouse tissues by demonstrating that a DNA sequence introduced into the telomere can be copied from telomere to telomere. We are developing this technology to further study how low levels of ALT activity can become sufficiently elevated to prevent telomere shortening and allow unlimited proliferation of cancer cells.
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See the Full NCBI Bibliography.
Cancer Research Unit formed at CMRI. Goal: to understand cancer cell immortalisation in sufficient detail to find new cancer therapies.
Discovered Alternative Lengthening of Telomeres (ALT) mechanism of telomere maintenance in cancer, opening up a new field of research.
Found diagnostic marker for ALT, called APBs. Also showed that unknown factors in normal cells can repress ALT cancers.
Demonstrated that ALT involves DNA recombination. First in the world to show this underlying mechanism.
First in world to identify the composition of active telomerase enzyme complex in human cells.
Developed C-circle assay for measuring ALT activity in cancer. Discovered telomere trimming mechanism that could one day be exploited to target and kill cancer cells.
C-circle assay licensed for research use as a test for ALT cancers. Also determined the number of ‘frayed’ telomere ends needed to signal senescence or cell aging.
Involved in international Starr Consortium study identifying key genetic change (loss of ATRX) in ALT.
Demonstrated that ALT has a normal counterpart in mouse cells, which also provides a new model system for studying the ALT mechanism.
Extend the utility of the C-circle assay for diagnostic use and to screen for ALT inhibitors. Study key ALT proteins to reveal potential therapeutic drug targets.