Dr Philippe Bouillet

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Division: Molecular Genetics of Cancer

Research Overview

There is good evidence that interfering with the Bcl-2-regulated pathway to cell death is a promising therapeutic approach. The race is now on to find small molecules, dubbed as “BH3-mimetics”, capable of either killing cancer cells directly or in combination with common chemotherapeutic drugs by acting on the Bcl-2-regulated pathway. Results emanating from our Division have shed light on the selective binding properties of the BH3-only proteins to pro-survival members of the Bcl-2 family, and shown the need for a better understanding of the properties and mechanisms of regulation of the BH3-only proteins.

Our present work is aimed at evaluating the importance in vivo of mechanisms of regulation that have so far been discovered and characterised only in vitro. Bim is the primary focus of our studies, because it plays a prominent role in the haematopoietic system, and is readily amenable to gene targeting. We have generated several mouse strains in which the Bim gene contains subtle mutations that address different mechanisms of regulation.

Research Interests

Selected Publications

Mérino D, Giam M, Hughes PD, Siggs OM, Heger K, O'Reilly LA, Adams JM, Strasser A, Lee EF, Fairlie WD, Bouillet P. The role of BH3-only protein Bim extends beyond inhibiting Bcl-2-like prosurvival proteins. J Cell Biol. 2009 Aug 10;186(3):355-362. PMID: 19651893
Hughes PD, Belz GT, Fortner KA, Budd RC, Strasser A, Bouillet P. Apoptosis regulators fas and bim cooperate in shutdown of chronic immune responses and prevention of autoimmunity. Immunity. 28(2):197-205, 2008. PMID: 18275830
Hughes P, Robati M, Lu W, Zhou J, Strasser A, Bouillet P. Loss of PKD1 and loss of Bcl-2 elicit polycystic kidney disease through distinct mechanisms. Cell Death Differ. 2006 Jul;13(7):1123-7 PMID: 16282979
Bouillet P, Robati M, Bath M, Strasser A. Polycystic kidney disease prevented by transgenic RNA interference. Cell Death Differ. 2005 Jul;12(7):831-3 PMID: 15818405
Tan TT, Degenhardt K, Nelson DA, Beaudoin B, Nieves-Neira W, Bouillet P, Villunger A, Adams JM, White E. Key roles of BIM-driven apoptosis in epithelial tumors and rational chemotherapy.
Cancer Cell. 2005 Mar;7(3):227-38 PMID: 15766661
Pellegrini M, Bouillet P, Robati M, Belz GT, Davey GM, Strasser A. Loss of Pro-Apoptotic BH3-Only Protein Bim Increases T Cell Production and Function in IL-7 Receptor-Deficient Mice. J Exp Med. 2004 Nov 1;200(9):1189-95. PMID:15504823
Egle A, Harris AW, Bouillet P, Cory S. Bim is a suppressor of Myc-induced mouse B cell leukemia. Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6164-9 PMID: 15079075
Bouillet P, Purton JF, Godfrey DI, Zhang LC, Coultas L, Puthalakath H, Pellegrini M, Cory S, Adams JM, Strasser A. BH3-only relative Bim is required for apoptosis of autoreactive thymocytes. Nature. 2002 Feb 21;415(6874):922-926. PMID: 11859372
Bouillet P, Cory S, Zhang LC, Strasser A, Adams JM. Degenerative disorders caused by Bcl-2 deficiency prevented by loss of its BH3-only antagonist. Dev. Cell. 2001 Nov;1(5):645-653. PMID: 11709185
Bouillet P, Metcalf D, Huang DCS, Tarlinton DM, Kay TWH, Koentgen F, Adams JM, Strasser A. Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis and to preclude autoimmunity. Science. 1999 Nov 26;286(5445):1735-1738.PMID: 10576740.

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Current Laboratory Members

Faculty Member: Phillipe Bouillet, PhD Louis Pasteur

Postdoctoral Fellow: Silvia Alvarez-Diaz PhD Madrid

Postdoctoral Fellow: Cyril Clybouw, BSc Paris VI MSc Paris XI PhD Paris XI

PhD student: Maybelline Giam, BSc Melb, (BSc Hons)

PhD student: Liz Valente BBiomedSc (Hons) LaTrobe

Honours student: Ryan Stuchbery, BSc Melb

Research Assistant: Bruno Helbert, MSc Paris-Sorbon

Research Assistant: Mikara Robati, BSc Waikato ne

Research Assistant: Carley Young, BSc Melb

The Walter and Eliza Hall Institute of Medical Research