Project Lead
Dr Thomas Lew
BIO
Blood cancers kill >4,500 Australians per year. A novel drug, venetoclax, has significantly improved outcomes for patients with several types of blood cancer, but relapses frequently occur. This PhD will analyse cancer cells at the single cell level to identify and specifically target the resistant populations that cause relapse. We will also study how another novel compound may synergise with venetoclax through targeting cancer cell metabolism. If successful, these projects may take critical steps towards new treatments for patients with blood cancers, and potentially curative novel drug combinations.
- Lew TE, Van Delft M, Riffkin C, Georgiou A, White C, Yuan Y, Jahja M, Anderson MA, Thijssen R, Huang DCS, Dawson MA, Roberts AW. Depletion of the mitochondrial E3 ligase MARCH5 induces synthetic lethality to BCL2 inhibitor (venetoclax) therapy in cell lines representative of diverse blood cancers.
- Lew TE*, Bennett R, Lin VS, Whitechurch A, Handunnetti SM, Marlton P, Shen Y, Mulligan SP, Casan J, Blombery P, Tam CS, Roberts AW, Seymour JF, Thompson PA, Anderson MA. Venetoclax-rituximab is active in patients with BTKi-exposed CLL, but durable treatment-free remissions are uncommon.
- Li K, Yap YQ, Moujalled DM, Sumardy F, Khakham Y, Georgiou A, Jahja M, Lew TE, De Silva M, Lou M, Gong J, Roberts AW, Loews K, Huang DCS, Kile B, Wei AH, Dewson G, van Delft MF, Lessene G. Differential regulation of BAX and BAK apoptotic activity revealed by a novel small molecule. Science Advances [under review]
- Luo M, Tan T, Trussart M, Poch A, Nguyen TMH, Speed TP, Hicks DG, Bandala-Sanchez E, Peng H, Chappaz S, Slade C, Utzschneider DT, Koldej R, Strasser A, Thijssen R, Ritchie ME, Tam CS, Lindeman G, Huang DCS,Lew TE, Anderson MA, Roberts AW, The CE, Gray DHD. Venetoclax Dose Escalation Rapidly Activates a BAFF/BCL-2 Survival Axis in Chronic Lymphocytic Leukemia. Blood [accepted].
- Lew TE*, Bennett R*, Lin VS, Whitechurch A, Handunnetti SM, Marlton P, Shen Y, Mulligan SP, Casan J, Blombery P, Tam CS, Roberts AW, Seymour JF, Thompson PA, Anderson MA. Venetoclax-rituximab is active in patients with BTKi-exposed CLL, but durable treatment-free remissions are uncommon. Blood Advances 8(6):1439-1443. [IF 7.637]T.E.L and R.B. contributed equally to this study.
- Lew TE*, Cliff ERS*, Dickinson M, Tam CS, Seymour JF, Blombery P, Bajel A, Ritchie D, Khot A. Allogeneic stem cell transplantation achieves long-term remissions in mantle cell lymphoma, including in TP53-mutated disease. Leukemia and Lymphoma 2:1-9. [IF 2.996].T.E.L and E.R.S.C contributed equally to this study.
- Lew TE*, Minson A*, Dickinson M, Handunnetti SM, Blombery P, Khot A, Anderson MA, Ritchie D, Tam CS, Seymour JF. A review of treatment approaches for patients with TP53-mutated mantle cell lymphoma. Lancet Haematology 10(2):e142-154 [IF 30.153] T.E.L and A.M. contributed equally to this study.
- Lew TE*, Seymour JF*. Clinical experiences with venetoclax and other pro-apoptotic agents in lymphoid malignancies: lessons from monotherapy and chemotherapy combination. Journal of Hematology and Oncology, 15(1):75 [IF 17.388]. T.E.L. and J.F.S. contributed equally to this study
- American Society of Hematology (ASH) Abstract Achievement Award – for trainees with high-scoring annual meeting abstracts
- Tour de Cure PhD scholarship ($10,000)
- National Health and Medical Research Council (NHMRC) postgraduate PhD scholarship ($139,535.48 over 3 years)
- Investigator and primary data contributor on 66Ten Tier 1 funded project: Developing a first-in-class inhibitor of the E3 ubiquitin ligase MARCH5 for sensitizing cancers to BH3 mimetic therapy (~$180,000 over 1 year)- WEHI Ventures
- Chief investigator B Cancer Council NSW Research Grant: MARCH5 is a master regulator of BCL2 proteins and a potential anti-cancer drug target ($450,000 over 3 years)
- Co-lead on 66Ten Tier 1 funded project: HLHPrime – A novel gene therapy platform to cure severe monogenic T cell diseases and develop “remote controllable” genetically engineered T cells ($105,000 over 1 year; inaugural recipient) - WEHI ventures
- Young investigator travel scholarship- International Workshop on Chronic Lymphocytic Leukaemia (iwCLL)