Professor David Huang
Details
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Division: Chemical Biology
Research Overview
The general long-term aim of the laboratories in the Molecular Genetics of Cancer Division is to understand how cancers arise and to develop better approaches for their diagnoses and treatment. In particular, Dr Huang and his team, in collaboration with several others in this Division as well as colleagues in the Structural Biology Division, is focused on understanding the regulation of apoptosis, the programmed death of cells, because its impairment often leads to cancer and renders the tumor cells resistant to standard chemotherapeutic drugs. Whether a cell lives or dies is critically determined by interactions between the three factions of the Bcl-2 protein family. Bcl-2 and the members most closely related to it promote cell survival by keeping the essential cell death mediators Bax and Bak in check, until overwhelmed by the killer BH3-only proteins, which are ligands of the pro-survival family members. Precisely how the pro-survival Bcl-2-like proteins keep Bax and Bak in check remains to be clarified, and how Bax and Bak act to cause cell death is also uncertain. Elucidating these steps in cell death signaling is essential for understanding how cell death is regulated physiologically. It is also highly pertinent to current efforts to develop compounds that directly target Bcl-2-like proteins as novel anti-cancer agents.
Selected Publications
- Huang DC, O'Reilly LA, Strasser A, Cory S. The anti-apoptosis function of Bcl-2 can be genetically separated from its inhibitory effect on cell cycle entry. EMBO J. 1997 Aug 1;16(15):4628-38 PMID: 9303307 [PubMed - indexed for MEDLINE]
- O'Connor L, Strasser A, O'Reilly LA, Hausmann G, Adams JM, Cory S, Huang DC. Bim: a novel member of the Bcl-2 family that promotes apoptosis. EMBO J. 1998 Jan 15;17(2):384-95 PMID: 9430630 [PubMed - indexed for MEDLINE]
- Huang DC, Hahne M, Schroeter M, Frei K, Fontana A, Villunger A, Newton K, Tschopp J, Strasser A. Activation of Fas by FasL induces apoptosis by a mechanism that cannot be blocked by Bcl-2 or Bcl-x(L). Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14871-6 PMID: 10611305 [PubMed - indexed for MEDLINE]
- Hausmann G, O'Reilly LA, van Driel R, Beaumont JG, Strasser A, Adams JM, Huang DC. Pro-apoptotic apoptosis protease-activating factor 1 (Apaf-1) has a cytoplasmic localization distinct from Bcl-2 or Bcl-x(L). J Cell Biol. 2000 May 1;149(3):623-34 PMID: 10791976 [PubMed - indexed for MEDLINE]
- Huang DC, Strasser A. BH3-Only proteins-essential initiators of apoptotic cell death. Cell. 2000 Dec 8;103(6):839-42 PMID: 11136969 [PubMed - indexed for MEDLINE]
- Marsden VS, O'Connor L, O'Reilly LA, Silke J, Metcalf D, Ekert PG, Huang DC, Cecconi F, Kuida K, Tomaselli KJ, Roy S, Nicholson DW, Vaux DL, Bouillet P, Adams JM, Strasser A. Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome. Nature. 2002 Oct 10;419(6907):634-7 PMID: 12374983 [PubMed - indexed for MEDLINE]
- Baell JB, Huang DC. Prospects for targeting the Bcl-2 family of proteins to develop novel cytotoxic drugs. Biochem Pharmacol. 2002 Sep;64(5-6):851-63 PMID: 12213579 [PubMed - indexed for MEDLINE]
- Hinds MG, Lackmann M, Skea GL, Harrison PJ, Huang DC, Day CL. The structure of Bcl-w reveals a role for the C-terminal residues in modulating biological activity. EMBO J. 2003 Apr 1;22(7):1497-507 PMID: 12660157 [PubMed - indexed for MEDLINE]
- Wilson-Annan J, O'Reilly LA, Crawford SA, Hausmann G, Beaumont JG, Parma LP, Chen L, Lackmann M, Lithgow T, Hinds MG, Day CL, Adams JM, Huang DC. Proapoptotic BH3-only proteins trigger membrane integration of prosurvival Bcl-w and neutralize its activity. J Cell Biol. 2003 Sep 1;162(5):877-87 PMID: 12952938 [PubMed - indexed for MEDLINE]
- Day CL, Chen L, Richardson SJ, Harrison PJ, Huang DC, Hinds MG. Solution structure of prosurvival Mcl-1 and characterization of its binding by proapoptotic BH3-only ligands. J Biol Chem. 2005 Feb 11;280(6):4738-44 PMID: 15550399 [PubMed - indexed for MEDLINE]
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Current Laboratory Members
Faculty Member: David Huang, MB BS MRCP PhD London
Senior Postdoctoral Fellow: Kylie Mason, FRACP MB BS PhD Melb FRCPA; Jointly with Cancer & Haematology Division
Postdoctoral Fellow: Brooke Cody
Postdoctoral Fellow: Kym Lowes, BSc(Hons) PhD UWA
Postdoctoral Fellow: Toru Okamoto, PhD Osaka
Postdoctoral Fellow: Megumi Takiguchi, BSc Victoria PhD Oxon
(Jointly with Molecular Medicine Division)
Postdoctoral Fellow: Monica Yabal, PhD Helsinki
Postgraduate Student: Seong Khaw, MB BS(Hons) Adelaide
(Jointly with Cancer & Haematology Division)
Undergraduate Student: Michael White, BBus BSc Swinburne
(Jointly with Molecular Medicine Division)
Undergraduate Student: Mohammed Yassin, BBiomedSc Melb
Research Assistant: Amandine Carmagnac, BSc France
Research Assistant: Angela Georgiou
Research Assistant: Helen Ierino, BAppSc RMIT