Cancer |
Our laboratory utilises a variety of in vitro, ex vivo and in vivo techniques to dissect out the role of key transporters and metabolic enzymes in cancer growth. We have determined a number of metabolic pathways that are differentially regulated in breast cancer, prostate cancer, melanoma and more recently glioblastoma. In particular, we are developing new physiological cancer models that more accurately reflect the metabolic microenvironment in vivo, and using these ex vivo models for therapeutic development, biomarker analysis and ultimately for personalised medicine approaches.
Current projects
The Translational Cancer Metabolism Laboratory is focused on understanding the role of amino acid uptake and metabolism in melanoma, breast and prostate cancer. The lab examines the basic biology regulating amino acid transporter expression and function, the downstream metabolic pathways, as well as developing new therapeutics to target the transporters and metabolic processes. We have also developed, together with Dr Omid Faridani at UNSW Sydney, the Ex Vivo Clinical Trial Platform (EViCT Platform) which enables physiological culture of patient tumour samples for drug testing.
Our current projects include:
- Medical Research Future Fund project where we are examining whether targeting androgen receptor signaling in glioblastoma, in combination with standard-of-care therapies, might be effective. We are using our novel physiological EViCT Platform explant culture system as well as animal models for this study in collaboration with A/Prof Christine Chaffer at the Garvan Institute.
- National Breast Cancer Foundation of Australia funded project where we are using the physiological EViCT Platform to examine targeting of triple-negative breast cancer metabolic vulnerabilities.
- Cancer Council NSW funded project together with Dr Margaret Centenera at SAHMRI in Adelaide where we are using the physiological EViCT Platform to examine metabolic targeting strategies in prostate cancer.
- Tour de Cure funded project where we are further developing the physiological EViCT Platform across a range of cancers including melanoma, with additional SPHERE funding for examining immunotherapy responses in melanoma patient samples using EViCT.
Highlighted publications
- Quek LE, van Geldermalsen M, Guan YF, Wahi K, Mayoh C, Balaban S, Pang A, Wang Q, Cowley MJ, Brown KK, Turner N, Hoy AJ, Holst J. Glutamine addiction promotes glucose oxidation in triple-negative breast cancer. Oncogene, Jul 18, 2022 http://dx.doi.org/10.1038/s41388-022-02408-5
- Wang Q, Guan YF, Hancock SE, Wahi K, van Geldermalsen M, Zhang BK, Pang A, Nagarajah R, Mak B, Freidman N, Horvath LG, Turner N, Holst J. Inhibition of guanosine monophosphate synthetase (GMPS) blocks glutamine metabolism and prostate cancer growth. Journal of Pathology. 254(2):135-146, 2021 http://dx.doi.org/10.1002/path.5665
- van Geldermalsen M, Wang Q, Nagarajah R, Marshall A, Thoeng A, Gao D, Ritchie W, Feng Y, Bailey CG, Deng N, Harvey K, Beith JM, Selinger C, O’Toole S, Rasko JEJ, Holst J. ASCT2/SLC1A5 controls glutamine uptake and tumour growth in triple-negative basal-like breast cancer. Oncogene, 35(24):3201-8, 2016 http://dx.doi.org/10.1038/onc.2015.381
- Wang Q, Tiffen J, Bailey CG, Lehman ML, Ritchie W, Fazli L, Metierre C, Feng Y, Li E, Gleave M, Buchanan G, Nelson CC, Rasko JEJ and Holst J. Targeting amino acid transport in metastatic castration-resistant prostate cancer: Effects on cell cycle, cell growth and tumor development. Journal of the National Cancer Institute 105(19):1463-73, 2013 http://dx.doi.org/10.1093/jnci/djt241
- Wang Q, Bailey CG, Ng C, Tiffen J, Thoeng A, Minhas V, Lehman ML, Hendy SC, Buchanan G, Nelson CC, Rasko JEJ and Holst J. Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport in prostate cancer progression. Cancer Research 71(24):7525-36, 2011 http://dx.doi.org/10.1158/0008-5472.CAN-11-1821
Our experts
Jeff Holst - Group Leader
Professor Jeff Holst leads the Translational Cancer Metabolism Laboratory at the University of NSW. Jeff completed his PhD at the University of NSW and undertook postdoctoral studies at St Jude Children’s Research Hospital. In 2006 he started a lab at the Centenary Institute focusing on the role of amino acid transport in cancer. In 2018, he moved to the University of NSW where he continues his work understanding the role of amino acid uptake and metabolism in melanoma, glioblastoma, breast and prostate cancer, with a particular focus on glutamine metabolism. His work examines the basic biology regulating amino acid transporter expression and function, the downstream metabolic pathways, as well as developing new therapeutic models and novel strategies to target these pathways.
Team members
- Dr Kanu Wahi
- Dr Kate Guan
- Ella Gray
- Michelle Devadason
- Jenny Wang
Honor students
- Bleron Zajmi
- Emily Huynh
Research Theme