Garvan Institute of Medical Research
The focus of my research is to discover the ways in which cancer cells avoid death, survive, grow and resist therapy. By understanding these mechanisms I aim to discovery new therapeutic strategies capable of eradicating disease in patients diagnosed with breast cancer. I hope to refine these new therapies in combination with conventional chemotherapy and target them to cancer cells so that patients will no longer have to suffer the burden of the dose limiting toxic side effects so commonly associated with routine cancer treatment.Other research projects include understanding the cues that regulate mammary development as these mechanisms may be dysregulated during breast cancer progression. I have contributed to the understanding of the regulation of mammary alveolar differentiation and demonstrated that the transcription factor Elf5 is the master regulator of the alveolar (milk producing) cell lineages during pregnancy. Importantly we discovered that Elf5 segregates with the steroid receptor positive cells in the mammary gland. This work has continued in my parent laboratory where we are now translating these findings for human breast cancer and discovered that Elf5 similarly drives anti-estrogen resistance in breast cancer. By targeting these mechanisms we may be able to alleviate the often fatal therapeutic resistant breast cancer recurrences that occur in a small proportion of patients treated with Tamoxifen.We further have discovered a novel gene called Jersey that is essential for mammary cell viability. Mutation of Jersey results in mammary cellular apoptosis resulting in severely perturbed alveolar functional differentiation and a consequent inability to nurse pups. Mutation of the Jersey gene results in constitutive activation of the Jersey pathway, never before linked to mammary development. The Jersey mutation also results in faster cancer growth.
mammary transplantation, cell sorting, cloning, FACS, Immunohistochemistry, mouse models, breast Cancer 2D and 3D tissue culture, western Blotting, pre-clinical mouse models, genetic engineering, quantitative PCR, genomics, confocal Microscopy, routine histology and microscopy
mouse models, 2D and 3D breast cancer models, patient derived xenografts