Professor Jeff Holst | UNSW Research

Keywords

Fields of Research (FoR)

Cancer cell biology, Cancer therapy (excl. chemotherapy and radiation therapy), Medical biochemistry - amino acids and metabolites, Medical biochemistry and metabolomics

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Cancer and Related Disorders

Biography

I am a fundamental and translational cancer researcher developing new ways to profile and target metabolic pathways in melanoma, glioblastoma, breast cancer and prostate cancer. My research has focussed primarily on the role of uptake and metabolism of amino acids by cancer cells and how these integrate and cooperate with glucose metabolism to drive cell growth. My lab has developed a range of novel methods for exploring these metabolic...view more

I am Director of Engagement in the School of Biomedical Sciences at UNSW, and Director of the Adult Cancer Program. In addition, I am part of the Strategic Advisory Committee of the UNSW Cancer Theme.

My Grants

NHMRC/MRFF ABC Brain Cancer Grant, A new targeted combination therapy with matched biomarker to treat intractable glioblastoma. Jan 2023-Dec 2024 (CIA)

Cancer Council NSW Project Grant, Targeting the metabolic adaptations that drive anti-androgen resistance in prostate cancer. Jan 2023-Dec 2025 (CIA)

NBCF Investigator Initiated Grant, Using a physiological Ex Vivo Clinical Trial Platform to EViCT breast cancer. Jan 2023-Dec 2025 (CIA)

Tour de Cure Senior Research Grant, Developing the ultimate cancer "indoor trainer" setup to personalise cancer therapies. Jan 2023-Dec 2024 (CIA)

Charlie Teo Foundation Pilot Grant, Developing a metabolic roadmap to discover novel therapeutic avenues to starve glioblastoma. Jan 2021-Jun 2023 (CIA)

Tour de Cure Senior Research Grant, A new therapy targeting “gluttonous” prostate cancer cells Jan 2020-Dec 2020 (CIA)

Cancer Council NSW Project Grant, Targeting glutamine addiction of triple-negative breast cancer (TNBC). Jan 2018-Dec 2020 (CIA)

Cancer Council NSW Project Grant, Nutrient stress-mediated adaptive responses as novel targets in BRAF mutant melanoma. July 2017-Dec 2020 (CIA)

NHMRC/MRFF Lifting Clinical Trials and Registries Capacity Grant, Immunotherapy Targeting of Cytomegalovirus antigens in Glioblastoma: INTERROGATE-GBM. June 2018-June 2023 (CIC)

NHMRC Project Grant APP1144108 Metabolically Reprogramming the Stroma to Starve Pancreatic Tumours. Jan 2018-Dec 2020 (CID)

Avner Pancreatic Cancer Foundation, Starvation of pancreatic tumours by metabolically reprogramming both tumour and stromal cells. January 2019-December 2020 (CIC)

My Qualifications

BSc (Hons), PhD

My Research Activities

The Translational Cancer Metabolism Laboratory is focussed 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.

Key Publications:

Wahi K, Freidman N, Wang Q, Devadason M, Quek LE, Pang A, Lloyd L, Larance M, Zanini F, Harvey K, O'Toole S, Guan YF, Holst J. Macropinocytosis mediates resistance to loss of glutamine transport in triple-negative breast cancer. EMBO Journal. Oct 17. Online ahead of print. 2024

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, 41(34):4066-78, 2022.

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. The Journal of Pathology, 254(2):135-146, 2021.

Zhang BK, Moran AM, Bailey CG, Rasko JEJ, Holst J*, Wang Q*. EGF-activated PI3K/Akt signaling coordinates leucine uptake by regulating LAT3 expression in prostate cancer. Cell Communication and Signaling, 17(1):83, 2019. *=Co-Senior Author

van Geldermalsen M, Quek LE, Turner N, Freidman N, Pang A, Guan YF, Krycer JR, Ryan R, Wang Q, Holst J. Benzylserine inhibits breast cancer cell growth by disrupting intracellular amino acid homeostasis and triggering amino acid response pathways. BMC Cancer, 18(1):689, 2018.

Marshall AD, van Geldermalsen M, Otte NJ, Lum T, Vellozzi M, Thoeng A, Pang A, Nagarajah R, Zhang B, Wang Q, Anderson L, Rasko JEJ, Holst J. ASCT2 Regulates Glutamine Uptake and Cell Growth in Endometrial Carcinoma. Oncogenesis, 6(7):e367, 2017.

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.

Wang Q, Hardie R-A, Hoy AJ, van Geldermalsen M, Gao D, Fazli L, Sadowski MC, Balaban S, Schreuder M, Nagarajah R, Wong JJ-L, Metierre C, Pinello N, Otte, NJ, Lehman ML, Gleave M, Nelson CC, Bailey CG, Ritchie W, Rasko JEJ, Holst J. Targeting ASCT2-Mediated Glutamine Uptake Blocks Prostate Cancer Growth and Tumour Development. The Journal of Pathology 236(3):278-89, 2015.

Wang Q, Beaumont KA, Otte NJ, Font J, Bailey CG, van Geldermalsen M, Sharp DM, Tiffen JC, Ryan RM, Jormakka M, Haass NK, Rasko JEJ, Holst J. Targeting glutamine transport to suppress melanoma cell growth. International Journal of Cancer 135(5):1060-71, 2014.

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 JEJand 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.

Wong JJ-L, Ritchie W, Ebner OA, Selbach M, Wong JWH, Huang Y, Gao D, Pinello N, Gonzalez M, Baidya K, Thoeng A, Khoo T-L, Bailey CG, Holst J* and Rasko JEJ*. Orchestrated intron retention regulates normal granulocyte differentiation. Cell. 154(3) 583-595, 2013.

Wang Q, Bailey CG, Ng C, Tiffen J, Thoeng A, Minhas V, Lehman ML, Hendy SC, Buchanan G, Nelson CC, Rasko JEJand 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