PhD Projects: Finding cures for breast and prostate cancer using computational biology and bioinformatics
Job No:
G12
Location:
Darlinghurst, Sydney
Supervisor: Associate Professor Alex Swarbrick
The Swarbrick lab is a multidisciplinary group with the mission to develop new treatment strategies for breast and prostate cancer, melanoma and the childhood cancer neuroblastoma. We study human disease and mouse models using advanced cell biology, immunology, molecular biology and computational methods.
We are leaders in the application of single cell genomics to oncology 1-3. Single cell genomics is revolutionizing our understanding of cell biology, immunology and genomics and promises to fuel a new generation of biological insights and treatments for cancer. We have developed and optimised methods to permit multi-parameter single cell analysis, measuring whole transcriptomes, hundreds of protein markers and targeted genome sequences from thousands of cells per sample.
We have opportunities for postgraduate students interested in applying/developing computational methods to explore the exciting challenges and opportunities presented by our very large single cell genomics datasets. Students will be co-supervised by a postdoctoral computational biologist in the lab, and opportunities exist for co-supervision by our close collaborator A/Prof Joseph Powell, one of Australia’s leading bioinformaticians.
The following broad project areas are active in the lab:
- Breast and Prostate cancer cell atlases. Our limited understanding of the tumour microenvironment (TME) has held back the development and implementation of new drugs that target stromal and immune cells. In this revolutionary project, we will use single cell genomics to characterise the TME and neoplastic heterogeneity in hundreds of early and metastatic breast and prostate cancers with rich clinico-pathological annotation that we have prospectively banked for this purpose. From these insights, we will discover cellular, genetic and transcriptional features shaping tumour biology and identify therapeutic vulnerabilities and novel treatment strategies.
- Smoothened inhibitors for the treatment of breast and prostate cancer. We have previously shown that a significant proportion of breast and prostate cancers secrete high levels of the embryonic morphogen ‘hedgehog’5,6. Hedgehog ligand activates adjacent stromal cells via Patched-Smoothened signaling, driving stromal fibroblasts to secrete pro-tumour molecules. Blocking this signaling axis with smoothened inhibitors destroys the ‘niche’ that protects cancer cells from treatment in mouse models and in humans4. We now aim to define the precise mechanism by which this elegant paracrine signaling system works in breast and prostate cancer, using single cell genomics in model systems and humans.
- Identify novel immunotherapy strategies in breast cancer. Immunotherapy has revolutionized the treatment of some cancers, such as melanoma, where up to 50% of patients with metastatic disease have significant long-term responses to treatment. Unfortunately, many cancers such as breast and prostate cancer exhibit innate resistance to currently approved immunotherapies, probably because we know very little about the immune milieu of these cancers. We are studying human specimens and immunocompetent mouse models to define the immune environment of these cancers and identify mechanisms of immune escape, with the aim of developing rational immunotherapy strategies.
About the lab
Alex Swarbrick is co-Leader of the Breast Translational Oncology Program in the Kinghorn Cancer Centre, Associate Professor of Medicine at UNSW and NHMRC Senior Research Fellow.
https://www.garvan.org.au/people/aleswa
The lab typically contains 1-2 clinical fellows, 3-4 postdoctoral fellows, 3-4 research assistants and 3-4 PhD & masters students.
https://www.garvan.org.au/research/cancer/tumour-progression
We are a friendly & fun lab with the determination to make a lasting impact on cancer biology and medicine. The lab is stable & well funded and a great place for ambitious science, computing and medicine graduates to pursue postgraduate and postdoctoral training.
Learn more about the lab:
https://twitter.com/dralexswarbrick
https://www.facebook.com/SwarbrickLab/
Selected papers
1 Roden, D. L. et al. Single cell transcriptomics reveals molecular subtype and functional heterogeneity in models of breast cancer. bioRxiv, doi:https://doi.org/10.1101/282079 (Preprint).
2 Junankar, S. et al. ID4 controls mammary stem cells and marks breast cancers with a stem cell-like phenotype Nature Communications 6, 6548 (2015).
3 Singh, M. et al. High-throughput targeted long-read single cell sequencing reveals the clonal and transcriptional landscape of lymphocytes. BioRxiV, doi:Https://doi.org/10.1101/424945 (Preprint).
4 Cazet, A. S. et al. Targeting stromal remodeling and cancer stem cell plasticity overcomes chemoresistance in triple negative breast cancer. Nat Commun 9, 2897, doi:10.1038/s41467-018-05220-6 (2018).
5 Hui, M. et al. The Hedgehog signalling pathway in breast development, carcinogenesis and cancer therapy. Breast Cancer Res 15, 203, doi:10.1186/bcr3401 (2013).
6 O'Toole, S. A. et al. Hedgehog overexpression is associated with stromal interactions and predicts for poor outcome in breast cancer. Cancer Research 71, 4002-4014, doi:10.1158/0008-5472.CAN-10-3738 (2011).