We are interested in understanding the regulation of RNA and how this is important in normal development and cancer. It is now appreciated that RNA is actively regulated at many levels and this is important for the function both normal cells and in cancer.
We are interested in how RNA editing by ADAR proteins changes the RNA landscape and contributes to normal physiology and cancer. We are also interested in why RNA splicing mutations are so important in the formation of blood cancers, in particular myelodysplastic syndrome. We use the models we generate to identify and develop new therapies for cancer. In a separate theme, we have established faithful small animal models of osteosarcoma, a bone cancer that occurs predominantly in teenagers, and are using this model to determine processes involved in the initiation, progression and metastasis of this cancer.
If you are interested in our work and are seeking Honours or PhD opportunities please contact Carl Walkley on [email protected] to enquire about available projects.
ADAR proteins catalyse the conversion of adenosine bases in RNA to inosine (termed A-to-I editing). We have used mouse genetics to define the role of Adar1 in vivo, demonstrating that the editing of RNA by ADAR1 is essential to prevent activation of the innate immune sensing system by endogenous RNA. We are continuing to study the role of A-to-I editing in both normal physiology and disease.
Myelodysplastic syndrome (MDS) and myelodysplastic/myeloproliferative syndromes (MDS/MPN) are a group of haematological cancers which are predominantly diseases of aging. The only curative treatment, bone marrow transplantation, is unavailable to most patients due to unacceptably high treatment-related mortality in the elderly. Whilst a catalogue of mutations in these cancers is established, how these mutations contribute to disease initiation, maintenance and ultimate evolution is much less clear. We have developed a humanized model of a common mutation found the RNA splicing machinery and are using this to understand how this mutations causes MDS and MDS/MPN.
Osteosarcoma is the most common tumour of bone. We have developed and characterized a unique model of this tumour based on our understanding of the human disease. This model closely mirrors the human disease in terms of histology, transcriptional profile, cytogenetics and metastatic dissemination. We are using this faithful model of human osteosarcoma to further understand the genetics of this disease as well as a pre-clinical model to explore new therapeutic approaches to treat both primary and metastatic disease.