STAT Cancer Biology

STAT Cancer Biology Research Group

Research Group Head

dan-goughs-labIntracellular signal transduction pathways affect diverse cell functions such as proliferation, death, differentiation, metabolism, and immune responses. Alterations in these pathways drive many diseases including cancer. The STAT Cancer Biology group focus on defining how the disruption of signalling, through the critical STAT family of proteins, alters the onset and progression of tumours.

The STAT Biology Group uses biochemical, cell biological and genomic approaches to define fundamental biochemical pathways, which engage the STAT proteins and apply this knowledge to mouse models of cancer.

Students projects are available in the following research themes:

Mitochondrial STAT3:  STAT3 is a crucial transcription factor with pleotropic biological functions. In addition to its potent nuclear activity there is a small but significant pool of STAT3 that translocates into the mitochondria. Mitochondrial STAT3 regulates the activity of the electron transfer chain and the opening of the mitochondrial permeability transition pore. This results is altered mitochondrial membrane potential, production of reactive oxygen species, ATP and resistance to death. This mitochondrial activity is required for transformation by the Ras family of oncogenes which contribute to ~25% of all human tumours. Yet despite this critical observation we have limited mechanistic insight into STAT3 mitochondrial import and activity and we use mass-spectrometry, biochemistry and animal models of cancer to address these questions.

STAT3 in Childhood Tumours:  Medulloblastoma is the most common childhood malignant brain tumour, and represents 20% of all paediatric central nervous system neoplasms. Although advances in surgery, radiation and chemotherapy have improved overall survival, the lifelong sequelae of these treatments represent a major health care burden for patients, parents, and society. Recent progress in the molecular subtyping of medulloblastoma have revealed four distinct subsets of tumours (WNT, sonic hedgehog (SHH), Group 3 and Group 4) with dramatically different biology. Research in our laboratory investigates the requirement for STAT3 in each this disease and whether STAT3 dependent biological processes can be targeted using existing inhibitors potentially leading to new therapeutic approaches

Small Cell Lung Cancer:  Lung cancer is by far the commonest cause of cancer-related death. Small cell lung cancer (SCLC) is a highly malignant neuroendocrine tumour that makes up 15-20% of the 9,700 Australians dying every year from lung cancer. Although SCLC is often sensitive to platinum-based chemotherapy at presentation, a secondary drug-resistant recurrence occurs in almost all cases, leading to a dismal overall 5-year survival rate of less than 5%. Despite SCLC being the 6th leading cause of cancer mortality in Australia, no effective new therapy for SCLC has been identified in the last 3 decades. Identfiying the mechanisms that drive platinum resistance and new compounds to overcome this resistance is a critical knowledge gap and a focus of our research group.

Research Group