Anne Brunet

Honors and Awards

• Junior Investigator Award, California Institute for Regenerative Medicine (CIRM) (2008-2013)
• Innovation in Aging Research Award, Pfizer/American Association for Aging Research (2005-2007)
• Klingenstein Fellow, The Esther A. & Joseph Klingenstein Fund (2005-2008)
• Alfred P. Sloan Fellow, Sloan Foundation (2006-2008)
• Glenn Award, The Glenn Foundation for Medical Research (2007)

Professional Education

• B.Sc., Ecole Normale Superieure, Paris Molecular Biology (1992)
• Ph.D., University of Nice, France Cell Biology (1997)
• Postdoctoral fellow, Harvard Medical School Neuroscience (2003)

Postdoctoral Advisees

• Hirokazu Fukui, Travis Maures, Dervis Salih, Dario Valenzano, Ashley Webb

Graduate & Fellowship Program Affiliations

• Cancer Biology
• Genetics
• Neurosciences

Web Site Links

• Brunet Lab Home Page

Research Interests

The overall goal of our lab is to understand the molecular mechanisms of longevity. Organismal longevity is regulated by a combination of genetic and environmental factors. Components of the signaling pathway that connect insulin to FOXO transcription factors (FOXOs) and SIRT deacetylases play a conserved role in the regulation of aging. However, how these pathways function to regulate lifespan is not well understood yet.

A first goal of the laboratory is to determine the molecular mechanisms of action of known longevity genes (FOXO and SIRT) in mammalian cells. We are particularly interested in deciphering the molecular logic by which these longevity genes translate environmental stimuli into changes in gene expression programs. We are using a combination of molecular, cellular, and high throughput genomic approaches to analyze the recruitment of these longevity genes to the chromatin in response to environmental stimuli, including nutrient stress, oxidative stress, and DNA damage.

A second focus of the laboratory is to determine the role of FOXOs in mammals, focusing on the nervous system. We are particularly interested in understanding the mechanisms of regulation of neural stem cells in the brain and in harnessing the regenerative potential of these cells. We are using a combination of mouse genetic approaches with the Cre/loxP recombination system and RNA interference approaches to perturb the expression of the FOXO and SIRT families in mice. We are studying the effect of these perturbations on the self-renewal and multipotency of neural stem cells in vitro and in vivo and on cognitive functions known to be affected with age, including learning and memory.

Finally, we are seeking to identify novel genes and processes that play an important role in aging. We are using genetics in the invertebrate worm C. elegans to identify the mechanisms of longevity induced by dietary restriction as well as to test the role of chromatin in the aging process. We are also developing a new model system for aging, the extremely short-lived African killifish N. furzeri to identify genes involved in longevity using a quantitative trait loci (QTL) analysis.

Publications

• Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans. Greer EL,  Brunet A.  Aging Cell.  2009; 8 (2): 113-27
• Cancer: When restriction is good. Brunet A,  Nature.  2009; 458 (7239): 713-4
• Mapping Loci Associated with Tail Color and Sex Determination in the Short-Lived Fish Nothobranchius furzeri. Valenzano DR,  Kirschner J, Kamber RA, Zhang E, Weber D, Cellerino A, Englert C, Platzer M, Reichwald K, Brunet A.  Genetics.  2009;
• FoxO3 regulates neural stem cell homeostasis. Renault VM,  Rafalski VA, Morgan AA, Salih DA, Brett JO, Webb AE, Villeda SA, Thekkat PU, Guillerey C, Denko NC, Palmer TD, Butte AJ, Brunet A.  Cell Stem Cell.  2009; 5 (5): 527-39
• An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans. Greer EL,  Dowlatshahi D, Banko MR, Villen J, Hoang K, Blanchard D, Gygi SP, Brunet A.  Curr Biol.  2007; 17 (19): 1646-56
• Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Brunet A,  Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, Greenberg ME.  Science.  2004; 303 (5666): 2011-5
• AMP-activated protein kinase and FoxO transcription factors in dietary restriction-induced longevity. Greer EL,  Banko MR, Brunet A.  Ann N Y Acad Sci.  2009; 1170 688-92
• Signaling networks in aging. Greer EL,  Brunet A.  J Cell Sci.  2008; 121 (Pt 4): 407-12
• FoxO transcription factors in the maintenance of cellular homeostasis during aging. Salih DA,  Brunet A.  Curr Opin Cell Biol.  2008; 20 (2): 126-36
• The FoxO code. Calnan DR,  Brunet A.  Oncogene.  2008; 27 (16): 2276-88
• FOXO transcription factors in ageing and cancer. Greer EL,  Brunet A.  Acta Physiol (Oxf).  2008; 192 (1): 19-28
• The energy sensor AMP-activated protein kinase directly regulates the mammalian FOXO3 transcription factor. Greer EL,  Oskoui PR, Banko MR, Maniar JM, Gygi MP, Gygi SP, Brunet A.  J Biol Chem.  2007; 282 (41): 30107-19
• FOXO transcription factors. Carter ME,  Brunet A.  Curr Biol.  2007; 17 (4): R113-4
• Ageing: from stem to stern. Brunet A,  Rando TA.  Nature.  2007; 449 (7160): 288-91
• Aging and cancer: killing two birds with one worm. Brunet A,  Nat Genet.  2007; 39 (11): 1306-7
• FOXO transcription factors at the interface between longevity and tumor suppression. Greer EL,  Brunet A.  Oncogene.  2005; 24 (50): 7410-25
• PEA-15 binding to ERK1/2 MAPKs is required for its modulation of integrin activation. Chou FL,  Hill JM, Hsieh JC, Pouyssegur J, Brunet A, Glading A, Uberall F, Ramos JW, Werner MH, Ginsberg MH.  J Biol Chem.  2003; 278 (52): 52587-97
• The many forks in FOXO's road. Tran H,  Brunet A, Griffith EC, Greenberg ME.  Sci STKE.  2003; 2003 (172): RE5
• 14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport. Brunet A,  Kanai F, Stehn J, Xu J, Sarbassova D, Frangioni JV, Dalal SN, DeCaprio JA, Greenberg ME, Yaffe MB.  J Cell Biol.  2002; 156 (5): 817-28
• DNA repair pathway stimulated by the forkhead transcription factor FOXO3a through the Gadd45 protein. Tran H,  Brunet A, Grenier JM, Datta SR, Fornace AJ, DiStefano PS, Chiang LW, Greenberg ME.  Science.  2002; 296 (5567): 530-4
• Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a). Brunet A,  Park J, Tran H, Hu LS, Hemmings BA, Greenberg ME.  Mol Cell Biol.  2001; 21 (3): 952-65
• Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway. Brunet A,  Datta SR, Greenberg ME.  Curr Opin Neurobiol.  2001; 11 (3): 297-305
• Transforming growth factor beta enhances epithelial cell survival via Akt-dependent regulation of FKHRL1. Shin I,  Bakin AV, Rodeck U, Brunet A, Arteaga CL.  Mol Biol Cell.  2001; 12 (11): 3328-39
• Substrate recognition domains within extracellular signal-regulated kinase mediate binding and catalytic activation of mitogen-activated protein kinase phosphatase-3. Nichols A,  Camps M, Gillieron C, Chabert C, Brunet A, Wilsbacher J, Cobb M, Pouyssegur J, Shaw JP, Arkinstall S.  J Biol Chem.  2000; 275 (32): 24613-21
• Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Brunet A,  Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME.  Cell.  1999; 96 (6): 857-68
• Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms. Bonni A,  Brunet A, West AE, Datta SR, Takasu MA, Greenberg ME.  Science.  1999; 286 (5443): 1358-62
• Cellular survival: a play in three Akts. Datta SR,  Brunet A, Greenberg ME.  Genes Dev.  1999; 13 (22): 2905-27
• Nuclear translocation of p42/p44 mitogen-activated protein kinase is required for growth factor-induced gene expression and cell cycle entry. Brunet A,  Roux D, Lenormand P, Dowd S, Keyse S, Pouysségur J.  EMBO J.  1999; 18 (3): 664-74
• Growth factor-induced p42/p44 MAPK nuclear translocation and retention requires both MAPK activation and neosynthesis of nuclear anchoring proteins. Lenormand P,  Brondello JM, Brunet A, Pouysségur J.  J Cell Biol.  1998; 142 (3): 625-33
• [Signal transduction from the membrane to the nucleus: variations on common themes] Brunet A,  Bull Cancer.  1998; 85 (6): 527-37
• Involvement of extracellular signal-regulated kinase module in HIV-mediated CD4 signals controlling activation of nuclear factor-kappa B and AP-1 transcription factors. Briant L,  Robert-Hebmann V, Sivan V, Brunet A, Pouysségur J, Devaux C.  J Immunol.  1998; 160 (4): 1875-85
• Inhibition of the mitogen-activated protein kinase pathway triggers B16 melanoma cell differentiation. Englaro W,  Bertolotto C, Buscà R, Brunet A, Pagès G, Ortonne JP, Ballotti R.  J Biol Chem.  1998; 273 (16): 9966-70
• Mammalian MAP kinase modules: how to transduce specific signals. Brunet A,  Pouysségur J.  Essays Biochem.  1997; 32 1-16
• The dual specificity mitogen-activated protein kinase phosphatase-1 and -2 are induced by the p42/p44MAPK cascade. Brondello JM,  Brunet A, Pouysségur J, McKenzie FR.  J Biol Chem.  1997; 272 (2): 1368-76
• Identification of MAP kinase domains by redirecting stress signals into growth factor responses. Brunet A,  Pouysségur J.  Science.  1996; 272 (5268): 1652-5
• Cyclin D1 expression is regulated positively by the p42/p44MAPK and negatively by the p38/HOGMAPK pathway. Lavoie JN,  L'Allemain G, Brunet A, Müller R, Pouysségur J.  J Biol Chem.  1996; 271 (34): 20608-16
• B-Raf protein isoforms interact with and phosphorylate Mek-1 on serine residues 218 and 222. Papin C,  Eychène A, Brunet A, Pagès G, Pouysségur J, Calothy G, Barnier JV.  Oncogene.  1995; 10 (8): 1647-51
• [MAP kinase module: role in the control of cell proliferation] Brunet A,  Brondello JM, L'Allemain G, Lenormand P, McKenzie F, Pagès G, Pouysségur J.  C R Seances Soc Biol Fil.  1995; 189 (1): 43-57
• The mouse p44 mitogen-activated protein kinase (extracellular signal-regulated kinase 1) gene. Genomic organization and structure of the 5'-flanking regulatory region. Pagès G,  Stanley ER, Le Gall M, Brunet A, Pouysségur J.  J Biol Chem.  1995; 270 (45): 26986-92
• Constitutively active mutants of MAP kinase kinase (MEK1) induce growth factor-relaxation and oncogenicity when expressed in fibroblasts. Brunet A,  Pagès G, Pouysségur J.  Oncogene.  1994; 9 (11): 3379-87
• Constitutive mutant and putative regulatory serine phosphorylation site of mammalian MAP kinase kinase (MEK1). Pagès G,  Brunet A, L'Allemain G, Pouysségur J.  EMBO J.  1994; 13 (13): 3003-10
• Growth factor-stimulated MAP kinase induces rapid retrophosphorylation and inhibition of MAP kinase kinase (MEK1). Brunet A,  Pagès G, Pouysségur J.  FEBS Lett.  1994; 346 (2-3): 299-303
• Growth factors induce nuclear translocation of MAP kinases (p42mapk and p44mapk) but not of their activator MAP kinase kinase (p45mapkk) in fibroblasts. Lenormand P,  Sardet C, Pagès G, L'Allemain G, Brunet A, Pouysségur J.  J Cell Biol.  1993; 122 (5): 1079-88