STAT Cancer Biology

Research Group Head

Intracellular 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.

Student projects are available in the following research themes:

Oncogenic roles of STAT3: STAT3 is a critical signalling protein that is essential for life. It is required for the biological response to a diverse array of cytokines and growth factors which activate STAT3 via post-translational modifications – primarily phosphorylation. Once activated, STAT3 translocates into the nucleus to initiate the transcription of hundreds of genes necessary for proliferation, immune function, apoptosis, metabolism and differentiation. The activity of STAT3 is tightly controlled. Too little STAT3 expression or activation results in debilitating immune disorders, and over-expression or activation of STAT3 is observed in over 50% of human tumours where it correlates with worse prognosis. However, it is now emerging that in specific tumour types STAT3 can act as a tumour suppressor and that it has non-nuclear functions in the mitochondria that are critical for tumour development, however both of these novel aspects of STAT3 biology remain poorly understood. This arm of the STAT Cancer Biology lab combines sophisticated 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.

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. The majority of patients present in the clinic with extensive stage disease with wide-spread metastasis. The only treatment option for these patients in platinum-based chemotherapy. Although SCLC is often sensitive to 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 sixth leading cause of cancer mortality in Australia, no effective new therapy for SCLC has been identified in the last three decades. Our lab uses mouse models, high-throughput drug screening and genetic screening to understand the drivers of metastasis and platinum resistance in SCLC.

The images above show computed tomography (CT) scans of the lungs of a mouse model of platinum resistant small cell lung cancer. Normal lung is shown in red and tumour in green. Once tumour was detected (tumour onset) mice were treated with platinum and etoposide (Pt/etop), however no tumour regression was observed. Mice were then treated with a novel second line therapy and CT scans show the dramatic reduction in tumour burden.

Research Group