David Leaver

Dr David Leaver

Biochemist

Dentistry and Medical Sciences

Biography

David’s research focuses on the development of novel therapeutics that target specific proteins with the goal of improving the quality of life for people that suffer from life threatening diseases. David enjoys tackling difficult aspects of early-stage drug discovery with vibrant and rigorous research projects. David obtained his BSc (First Class Honours) and PhD from La Trobe University and he received the David Kelly Medal for being the best Honours student within the School of Molecular Sciences. David completed a postdoctoral research position in medicinal chemistry under the supervision of Professor Jonathan Baell at the Monash Institute of Pharmaceutical Sciences (MIPS) and he completed a second postdoctoral research position in chemical biology under the supervision of Professor W. David Nes at Texas Tech University that focused on ergosterol biosynthesis inhibitors. David’s translational success is illustrated by his key role in proving that KAT6A was indeed a druggable target as he co-designed and synthesized WM-8014. CTxONE (now OncologyOne) licensed KAT6A technology to Pfizer in 2018 and this deal is worth up to US$475M. PF-07248144 (KAT6A inhibitor) entered Phase 1 clinical trials in 2020 for the potential treatment of patients with cancer. David’s research interests include the development of novel biosynthesis inhibitors that could be used to treat cancer or parasitic protozoan diseases (Human African Trypanosomiasis & Chagas Disease), the development of synthetic carbohydrate biomimetics as urinary tract infection prophylactics and the synthesis of enzyme inhibitors that can be used to kill viruses and parasitic nematodes.

Collaborative research projects David has participated in have been published in a number of journals including Nature, Cell Metabolism and the Journal of Medicinal Chemistry (cover article).

Research
  • Chemical biology and epigenetics
  • Early-stage drug discovery
  • Enzyme inhibitors
  • Carbohydrate biomimetics
Publications
Full publications list on CRO

Recent publications

  • Nes, W. D., Chaudhuri, M., & Leaver, D. (2024). Druggable Sterol Metabolizing Enzymes in Infectious Diseases: Cell Targets to Therapeutic Leads. Biomolecules, 14, Article 249. https://doi.org/10.3390/biom14030249
  • Madan, B., Virshup, D. M., Nes, W. D., & Leaver, D. J. (2022). Unearthing the Janus-face cholesterogenesis pathways in cancer. Biochemical Pharmacology, 196(February), 1-13. [114611]. https://doi.org/10.1016/j.bcp.2021.114611
  • Zhou, W., Fisher, P. M., Vanderloop, B. H., Shen, Y., Shi, H., Maldonado, A. J., Leaver, D. J., & David Nes, W. (2020). A nematode sterol C4α-methyltransferase catalyzes a new methylation reaction responsible for sterol diversity. Journal of Lipid Research, 61(2), 192-204. https://doi.org/10.1194/jlr.RA119000317
  • MacPherson, L., Anokye, J., Yeung, M. M., Lam, E. Y. N., Chan, Y. C., Weng, C. F., Yeh, P., Knezevic, K., Butler, M. S., Hoegl, A., Chan, K. L., Burr, M. L., Gearing, L. J., Willson, T., Liu, J., Choi, J., Yang, Y., Bilardi, R. A., Falk, H., Nguyen, N., … Dawson, M. A. (2020). HBO1 is required for the maintenance of leukaemia stem cells. Nature, 577, 266-270. https://doi.org/10.1038/s41586-019-1835-6
  • Priebbenow, D. L., Leaver, D. J., Nguyen, N., Cleary, B., Lagiakos, H. R., Sanchez, J., Xue, L., Huang, F., Sun, Y., Mujumdar, P., Mudududdla, R., Varghese, S., Teguh, S., Charman, S. A., White, K. L., Shackleford, D. M., Katneni, K., Cuellar, M., Strasser, J. M., ... Baell, J. B. (2020). Discovery of acylsulfonohydrazide-derived inhibitors of the lysine acetyltransferase, kat6a, as potent senescence-inducing anti-cancer agents. Journal of Medicinal Chemistry, 63(9), 4655-4684. https://doi.org/10.1021/acs.jmedchem.9b02071