Targeting cancer metabolism to overcome therapy resistance in acute leukaemia

This project is suitable for Honours, Masters (by Research) and PhD students. Background Acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) remain among the most challenging blood cancers to treat. While targeted therapies and immunotherapies have improved outcomes, many patients relapse because therapy-resistant leukaemia cells survive within the protective bone marrow microenvironment. Our laboratory investigates how metabolic rewiring drives therapeutic resistance in acute leukaemia. We have demonstrated that AML and ALL are highly dependent on nicotinamide adenine dinucleotide (NAD) metabolism and have contributed to the preclinical and clinical development of the next-generation NAMPT inhibitor OT-82. Using clinically annotated patient-derived xenograft (PDX) models, we aim to identify metabolic vulnerabilities that can be exploited to develop more effective therapies for children and adults with high-risk acute leukaemia. Aim This project will investigate the metabolic mechanisms underlying response and resistance to NAD-targeted therapies using clinically relevant patient-derived models. Students will receive training in cutting-edge translational research techniques, including: establishment and treatment of patient-derived xenograft (PDX) models of AML and ALL evaluation of novel targeted therapy combinations, including OT-82 with venetoclax and other precision medicines single-cell metabolic profiling to define metabolic dependencies of therapy-resistant leukaemia cells flow cytometry, molecular biology and functional drug screening genomic, transcriptomic and metabolomic analyses to identify biomarkers predicting therapeutic response advanced ex vivo bone marrow models to investigate interactions between leukaemia cells and the tumour microenvironment. Depending on the level of the project (Honours or PhD), students may also have opportunities to participate in collaborative studies incorporating advanced imaging and multi-omic analyses to better understand treatment response in vivo. The project provides a unique opportunity to work within a highly translational research program with direct access to patient samples, clinically annotated PDX models, clinician scientists, and national and international collaborators. Findings from this work will contribute to the development of biomarker-driven therapies and future clinical trials for acute leukaemia. Minimum entry requirements can be found here: https://www.monash.edu/admissions/entry-requirements/minimum