Prof. Ravindra Majeti (Stanford University) and Assoc. Prof. Dan Thomas (South Australia Health Medical Research Institute)

Prof. Majeti and Assoc. Prof. Thomas recently discovered a strong link between the metabolism of leukemia cells and common leukemia-causing mutations through modulation of a central metabolic factor called alpha ketoglutarate. They have since developed innovative methods that can assess the fate of alpha ketoglutarate-dependent reactions on DNA, histones, lipid production, and energy metabolism. This research proposes to apply these methods to characterize acute myeloid leukaemia (AML) patient samples to inform a precision medicine therapy approach to treating the blood cancer. It also aims to investigate pharmacologic agents targeting the alpha ketoglutarate-dependent reactions. The objective of the research is to develop personalised medicine through metabolic targeting to deliver mutation-directed therapies to AML patients.

Prof. John Pimanda (University NSW)

The most effective medicine to treat myelodysplastic syndrome (MDS), azacitidine, works in only half of MDS and associated AML patients who commence treatment. Over the past decade, Prof. Pimanda and his team have identified treatment alternatives for patients who have been proven, or have potential to be, non-responsive to azacitidine. The research proposes to discover new medicine that improves azacitidine efficacy by using a novel chemical-genome screen using a MDS cell line to identify specific genes that can make MDS cells more sensitive to the medicine. This information will then be used to identify molecular pathways amenable to pharmacological manipulation to achieve the same effect. Efficacy of medicine combinations in enhancing azacitidine activity can then be assessed, using azacitidine non-responder MDS cells to undertake pre-clinical testing in preparation for a future clinical trial.

Total Project cost: $454,211 over three years
Funding received to date: $151,403
Seeking: $302,808 for Year 2 & Year 3 funding
Leverage: $4 for every $1 donated to Snowdome Foundation