Wei Group - Leukaemia Translational Research


2018 group L-R Back row: Mr Nik Cummings, Dr Adam Ivey, Ms Julie McManus, Dr Jess Salmon L-R Front row: Ms Rachel Xu, Dr Fiona Brown, Dr Donia Moujalled, Ms Veronique Litalien, A/Prof Andrew Wei Absent: Ms Sarah MacRaild, Ms Giovanna Pomilio, Dr Tse-Chieh Teh.

Research Interests

A/Prof Andrew Wei leads a translational research group focused on improving clinical outcomes for patients with acute myeloid leukaemia (AML). AML is an aggressive blood cancer that arises from the transformation of leukaemic stem cells. In most cases this is a multigenic process with over 200 recurrently mutated genes already identified. The evolution of AML is also multiclonal and likely responsible for the rapid development of drug resistance from evolving ancestral or leukaemic sub-clones. The leukaemia Translational Research Group seeks to identify critical targets associated with drug resistance, develop primary human models of AML to study new therapies and to identify novel combinations aimed at improving response depth and duration in patients with this disease. Our approach integrates pre-clinical with clinical research studies and collaborations with leading pharmaceutical groups in order to maximize research relevance and to narrow the gap from bench to bedside and back to the bench.
Prospective new PhD or honours students are invited to enquire about laboratory positions: Andrew.wei@monash.edu

Projects

  1. Targeting pro-survival BCL2 family members in AML
  2. Tracking the clonal evolution of leukaemia in acquired drug resistance
  3. Establishing patient-derived xenografts of AML using humanized mouse models
  4. Using gene editing technology to identify mechanisms of drug resistance
  5. Developing a high-throughput screen in primary AML cells to identify novel synthetic lethal drug combinations

Clinical Trials

  • 2016 Mapping the fate of IDH mutant AML in Australia
  • 2016 Chemotherapy and Venetoclax (ABT-199) in Elderly AML Trial (CAVEAT)
  • 2013 A phase Ib/II clinical evaluation of Ponatinib in combination with 5-azacytidine in patients with FLT3-ITD AML failing chemotherapy
  • 2012 A randomised study combining standard chemotherapy with the FLT3 inhibitor sorafenib or placebo in FLT3-ITD positive AML
  • 2011 A strategy of high-dose lenalidomide in combination with epigenetic therapies for relapsed and refractory MDS/AML
  • 2010 A phase Ib/II study of Lenalidomide maintenance in AML
  • 2009 Phase Ib/II Clinical Evaluation Of The Safety Of Combining the mTOR inhibitor Everolimus With 5-azacytidine In Elderly Patients With AML
  • 2009 A Phase Ib/II Clinical Evaluation Of The Safety Of Combining the Lenalidomide with 5-azacytidine as maintenance therapy in AML
  • 2008 A Phase 1 Dose Finding Study Of RAD001 In Elderly Patients With Acute Myeloid leukaemia (AML) Unfit For Intensive Induction Chemotherapy

Current Project Funding

  • 2014-2016  VCA TRANSLATIONAL RESARCH GRANT
    • BH3-mimetics in rational combination therapies to overcome treatment-resistant cancers
  • 2014-2016 NHMRC APP1066711
    • Targeting the apoptosis machinery in cancer
  • 2013-2017 NHMRC APP1048312
    • A randomised study to optimise clinical outcomes in patients with FLT3 mutant AML
  • 2012-2014 NHMRC APP1033248
    • Dual inhibition of independent cell survival pathways as a new approach for targeting leukaemic stem cells

Selected Recent Publications

  • Rijal, S., Fleming, S., Cummings, N., Rynkiewicz, N. K., Ooms, L. M., Nguyen, N.-Y. N., Teh, T.-C., Avery, S., McManus, J. F., Papenfuss, A. T., McLean, C., Guthridge, M., Mitchell, C., Wei, A. (2015). Inositol polyphosphate 4-phosphatase II (INPP4B) is associated with chemoresistance and poor outcome in AML. Blood 125, 2815-2824.
  • Thomas, D; Powell, J; Vergez, F; Segal, D; Nguyen, N; Baker, A; Teh, T; Barry, E; Sarry, J; Lee, E; Nero, T; Jabbour, A; Pomillio, G; Green, B; Manenti, S; Glaser, S; Parker, M; Lopez, A; Ekert, P; Lock, R; Huang, D; Nilsson, S; Récher, C; Wei, A; Guthridge, M (2013) Targeting acute myeloid leukaemia by dual inhibition of PI3K signalling and Cdk9-mediated Mcl-1 transcription. Blood, 122, 738-748.