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About

The long-term goals of my laboratory are to understand how cancers arise and to develop better approaches for their diagnosis and treatment. Our focus is on the regulation of apoptosis by the Bcl-2 family.

In collaboration with other scientists at the institute, members of my laboratory are unravelling the mechanisms by which members of the Bcl-2 family determine whether a cell lives or dies. Precisely how Bcl-2 restrains essential cell death mediators Bax and Bak is unclear and how Bax and Bak become activated to drive apoptosis is also uncertain. Elucidating the key steps in cell death signalling is essential for understanding how cell death is regulated physiologically.

We are actively translating the knowledge we have gained so far into efforts to target Bcl-2 or its pro-survival relatives for treating patients with cancers (e.g. leukaemias, lymphomas) and identifying potential mechanisms why such small molecule inhibitors might fail.

Publications

Selected publications from Prof David Huang

Brown FC, Wang X, Birkinshaw R, Chua CC, Morley T, Kasapgil S, Pomilio G, Blombery P, Huang DCS, Czabotar P, Priore SF, Yang G, Carroll M, Wei AH, Perl AE. Acquired BCL2 variants associated with venetoclax resistance in acute myeloid leukemia. Blood Advances. 2025;9(1):10.1182/bloodadvances.2024014446

Peng H, Jabbari JS, Tian L, Wang C, You Y, Chua CC, Anstee NS, Amin N, Wei AH, Davidson N, Roberts AW, Huang D, Ritchie ME, Thijssen R. Single-cell Rapid Capture Hybridization sequencing to reliably detect isoform usage and coding mutations in targeted genes. Genome Research. 2025;:10.1101/gr.279322.124

Luo M-X, Tan T, Trussart M, Poch A, Nguyen TMH, Speed TP, Hicks DG, Bandala-Sanchez E, Peng H, Chappaz S, Slade C, Utzschneider DT, Koldej RM, Ritchie D, Strasser A, Thijssen R, Ritchie ME, Tam CS, Lindeman GJ, Huang DCS, Lew TE, Anderson MA, Roberts AW, Teh CE, Gray DHD. Venetoclax dose escalation rapidly activates a BAFF/BCL-2 survival axis in chronic lymphocytic leukemia. Blood. 2024;144(26):10.1182/blood.2024024341

Gao M, Georgiou A, Lin VS, Jahja M, White CA, Anderson MA, McCormack MP, Roberts AW, Huang DCS, Thijssen R. Potential impact of NOTCH1 activation on venetoclax sensitivity in chronic lymphocytic Leukaemia: In vitro insights and clinical implications. British Journal of Haematology. 2024;205(4):10.1111/bjh.19604

Yuan Z, van Delft MF, Li MX, Sumardy F, Smith BJ, Huang DCS, Lessene G, Khakam Y, Jin R, He S, Smith NA, Birkinshaw RW, Czabotar PE, Dewson G. Key residues in the VDAC2-BAK complex can be targeted to modulate apoptosis. PLOS Biology. 2024;22(5):10.1371/journal.pbio.3002617

Wang Z, Burigotto M, Ghetti S, Vaillant F, Tan T, Capaldo BD, Palmieri M, Hirokawa Y, Tai L, Simpson DS, Chang C, Huang AS, Lieschke E, Diepstraten ST, Kaloni D, Riffkin C, Huang DCS, Suen CSNLW, Garnham AL, Gibbs P, Visvader JE, Sieber OM, Herold MJ, Fava LL, Kelly GL, Strasser A. Loss-of-Function but Not Gain-of-Function Properties of Mutant TP53 Are Critical for the Proliferation, Survival, and Metastasis of a Broad Range of Cancer Cells. Cancer Discovery. 2024;14(2):10.1158/2159-8290.cd-23-0402

Galas-Filipowicz D, Chavda SJ, Gong J-N, Huang DCS, Khwaja A, Yong K. Co-operation of MCL-1 and BCL-XL anti-apoptotic proteins in stromal protection of MM cells from carfilzomib mediated cytotoxicity. Frontiers in Oncology. 2024;14:10.3389/fonc.2024.1394393

Yang D, Li Q, Lu P, Wu D, Li W, Meng X, Xing M, Shangguan W, Chen B, Yang J, Zhang Z, Wang Z, Huang DCS, Zhao Q. FOXA2 activates HIF2α expression to promote tumor progression and is regulated by the E3 ubiquitin ligase VHL in renal cell carcinoma. Journal of Biological Chemistry. 2024;300(1):10.1016/j.jbc.2023.105535

Lew TE, Van Delft M, Riffkin C, Angela G, White C, Yuan Y, Michelle J, 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. Blood. 2023;142(Supplement 1):10.1182/blood-2023-184392

Xu J, Dong X, Huang DCS, Xu P, Zhao Q, Chen B. Current Advances and Future Strategies for BCL-2 Inhibitors: Potent Weapons against Cancers. Cancers. 2023;15(20):10.3390/cancers15204957

Lab research projects

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