Centre fpr Cancer Research Student Projects

Cancer & Developmental Biology Research Projects

Roles for the tumour suppressor gene Hic1 in development, differentiation and cancer
Project leader:  Prof Neil Watkins
Phone: 9594 7182

Hypermethylated in Cancer-1 (Hic1) is a unique tumour suppressor gene in that it is inactivated through deletion or epigenetic gene silencing, but not by mutation. It functions as a tumour suppressor by repressing expression of genes that are normally expressed in embryonic development, but not in adult tissues. Using mouse models, this project examines how Hic1 regulates gene expression during development, repair and tumour suppression. In addition, our Hic1 knockout is the only available mouse model to study epigenetic gene silencing in cancer. The potential projects would be the study of Hic1 in mouse development, targeted knockout of Hic1 in embryos and adult mice, and the study of how epigenetic silencing of Hic1 is triggered during tumour formation.


Interactions between Hedgehog and Ras signaling in lung adenocarcinoma
Project leader:  Prof Neil Watkins
Phone: 9594 7182

The Hedgehog (Hh) pathway is a highly conserved system for regulating cell fate and self- renewal in metazoans. Studies from my laboratory have also shown that this pathway plays an important role in cancer by sustaining the growth of tumour stem cells. To understand how the pathway initiates cancer, we have developed a series of mouse models in which we can conditionally activate expression of the Hh pathway in the lung of adult mice. In addition, we can also activate expression of the KRas oncogene in the same cells. Since activation of KRas initiates lung cancers in mice, we can use this model to understand how activation of Hh signaling in the lung cooperates with KRas to initiates tumour formation in lung cancer.


An in vivo model of acquired chemoresistance in small cell lung cancer (SCLC)
Project leader:  Prof Neil Watkins
Phone: 9594 7182

Small cell lung cancer (SCLC) is a common, highly metastatic cancer with an extremely poor prognosis. When first diagnosed, SCLC is usually extremely sensitive to platinum-based cytotoxic chemotherapy, with the majority of patients achieving a partial or complete clinical response Remarkably, little is known about the mechanisms of acquired chemoresistance in SCLC, or for that matter in most adult solid tumors. In part, this is due to the reliance on conventional cell line models of SCLC that may not reflect the responses of these tumors to chemotherapeutic agents in vivo.

This project uses a novel in vivo model of SCLC to investigate the mechanisms of acquired drug resistance in SCLC. In this model, we have generated a series of chemosensitive primary SCLC xenograft lines derived from chemo-naive patients and passaged exclusively in immunodeficient mice.

We will ask whether the process of acquiring chemo-resistance in SCLC is associated with a common set of genomic, epigenetic or transcriptional adaptations in vivo by tracking these changes during the acquisition of chemoresistance by serially sampling the same tumour.