Anne Brunet
Title
Assistant Professor
Department
Genetics
Research Interests
Molecular basis of longevity and age-dependent diseases.
Role of the nervous system in the control of lifespan.
Email
mailto:Anne.brunet@stanford.edu
Phone
725-8042
Fax
725-1534
Address
Always M336
Mail Code: 5120
Faculty Research Description
Aging was traditionally thought to be due to 'wear and tear' and was not believed to be a regulated process. However, this view has recently changed. A set of studies now indicates that longevity can be regulated by modifications in single genes or simple changes in the environment. To date, the signaling pathway connecting insulin, Akt, and FOXO transcription factors provides the most compelling example for a genetic pathway that controls lifespan. The overall objective of our research is to understand the role of FOXO transcription factors in mammalian longevity, with a particular focus on the importance of the nervous system in the control of lifespan.
A main project of the laboratory is to identify the molecular mechanisms by which FOXO transcription factors regulate a program of gene expression that promotes cellular resistance to oxidative stress, a process that is highly coupled with extended longevity. In particular, we use a combination of RNA interference and genomic approaches investigate the role of FOXO transcription factors and their protein partner, the longevity deacetylase Sir2, in the neuronal response to oxidative stress.
We also use proteomic approaches to identify more protein partners to which FOXO factors are recruited in response to various environmental stimuli that are known to affect longevity, including oxidative stress and caloric restriction. We believe that these approaches will reveal new components of the machinery that is important for organismal aging,
A primary goal of the laboratory is to use mouse models of FOXO transcription factors to study the importance of these factors at the organismal level. We use the CRE-lox technology combined with viral approaches to determine the importance of FOXO factors in the nervous system. We are also developing genetic approaches to test the importance of specific regions of the nervous system in organismal longevity.
With these studies, we hope to gain insight into the molecular mechanisms by which organismal lifespan is regulated, knowledge that will be critical for understanding and preventing age-dependent diseases, including neurodegenerative disorders.
http://www.stanford.edu/group/brunet
Brunet, A., Sweeney, L.B., Sturgill, F.J., Chua, K.F., Greer, P.L., Lin, Y., Tran, H., Ross, S.E., Mostoslavsky, R., Cohen, H., Hu, L.S., Cheng, H-L., Jedrychowsky, M., Gygi, S.P., Sinclair, D.A., Alt, F.W., Greenberg M.E. (2004) Stress-Dependent Regulation of FOXO transcription factors by the SIRT1 Deacetylase. Science 303: 2011-5.
Tran, H.*, Brunet A.*, Grenier, J.M., Datta, S.R., Fornace Jr., A.J., DiStefano, P.S., Chiang, L.W., Greenberg M.E. (2002) DNA repair pathway stimulated by the Forkhead transcription factor FOXO3a (FKHRL1) through the GADD45 protein. Science 296: 530-4.
Brunet A., Kanai, F., Stehn, J.Xu, J.Sarbassova, D.Frangioni, J.V.Dala, S.N.DeCaprio, J.A.Greenberg, M.E. Yaffe, M.B. (2002) 14-3-3 Transits to the Nucleus and Actively Participates in Dynamic Nucleo-Cytoplasmic Transport. J. Cell Biol. 156: 817-828.
Brunet A., Datta S.R. and Greenberg M.E. (2001) Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway. Curr.Opin. Neurobiology. 11: 297-305.
Brunet A., Bonni A., Zigmond M.J., Lin M.Z., Juo P., Hu L.S., Anderson M,J,, Arden K.C., Blenis J., Greenberg M.E. (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96: 857-868.
Bonni A., Brunet A., West A.E., Datta S.R., Takasu M.A., Greenberg M.E. (1999) Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and transcription-independent mechanisms. Science 286: 1358-1362.
Areas of Study
Cellular Neurobiology
Molecular Neurobiology
SBRC
PhD