Honors & Awards

  • J. E. Wallace Sterling Award for Scholastic Achievement, Stanford University (2010)
  • Firestone Medal for Excellence in Undergraduate Research, Stanford University (2010)

Education & Certifications

  • Bachelor of Science, Stanford University, MATH-MIN (2010)
  • Bachelor of Science, Stanford University, BIOL-BSH (2010)

Research & Scholarship

Current Research and Scholarly Interests

Aging reversal in stem cells, DNA methylation, skeletal muscle repair

Lab Affiliations


All Publications

  • mTORC1 controls the adaptive transition of quiescent stem cells from G0 to G(Alert). Nature Rodgers, J. T., King, K. Y., Brett, J. O., Cromie, M. J., Charville, G. W., Maguire, K. K., Brunson, C., Mastey, N., Liu, L., Tsai, C., Goodell, M. A., Rando, T. A. 2014; 510 (7505): 393-396


    A unique property of many adult stem cells is their ability to exist in a non-cycling, quiescent state. Although quiescence serves an essential role in preserving stem cell function until the stem cell is needed in tissue homeostasis or repair, defects in quiescence can lead to an impairment in tissue function. The extent to which stem cells can regulate quiescence is unknown. Here we show that the stem cell quiescent state is composed of two distinct functional phases, G0 and an 'alert' phase we term GAlert. Stem cells actively and reversibly transition between these phases in response to injury-induced systemic signals. Using genetic mouse models specific to muscle stem cells (or satellite cells), we show that mTORC1 activity is necessary and sufficient for the transition of satellite cells from G0 into GAlert and that signalling through the HGF receptor cMet is also necessary. We also identify G0-to-GAlert transitions in several populations of quiescent stem cells. Quiescent stem cells that transition into GAlert possess enhanced tissue regenerative function. We propose that the transition of quiescent stem cells into GAlert functions as an 'alerting' mechanism, an adaptive response that positions stem cells to respond rapidly under conditions of injury and stress, priming them for cell cycle entry.

    View details for DOI 10.1038/nature13255

    View details for PubMedID 24870234

  • Alive and well? Exploring disease by studying lifespan CURRENT OPINION IN GENETICS & DEVELOPMENT Brett, J. O., Rando, T. A. 2014; 26: 33-40
  • Expansion of oligodendrocyte progenitor cells following SIRT1 inactivation in the adult brain. Nature cell biology Rafalski, V. A., Ho, P. P., Brett, J. O., Ucar, D., Dugas, J. C., Pollina, E. A., Chow, L. M., Ibrahim, A., Baker, S. J., Barres, B. A., Steinman, L., Brunet, A. 2013; 15 (6): 614-624


    Oligodendrocytes-the myelin-forming cells of the central nervous system-can be regenerated during adulthood. In adults, new oligodendrocytes originate from oligodendrocyte progenitor cells (OPCs), but also from neural stem cells (NSCs). Although several factors supporting oligodendrocyte production have been characterized, the mechanisms underlying the generation of adult oligodendrocytes are largely unknown. Here we show that genetic inactivation of SIRT1, a protein deacetylase implicated in energy metabolism, increases the production of new OPCs in the adult mouse brain, in part by acting in NSCs. New OPCs produced following SIRT1 inactivation differentiate normally, generating fully myelinating oligodendrocytes. Remarkably, SIRT1 inactivation ameliorates remyelination and delays paralysis in mouse models of demyelinating injuries. SIRT1 inactivation leads to the upregulation of genes involved in cell metabolism and growth factor signalling, in particular PDGF receptor α (PDGFRα). Oligodendrocyte expansion following SIRT1 inactivation is mediated at least in part by AKT and p38 MAPK-signalling molecules downstream of PDGFRα. The identification of drug-targetable enzymes that regulate oligodendrocyte regeneration in adults could facilitate the development of therapies for demyelinating injuries and diseases, such as multiple sclerosis.

    View details for DOI 10.1038/ncb2735

    View details for PubMedID 23644469

  • The MicroRNA Cluster miR-106b similar to 25 Regulates Adult Neural Stem/Progenitor Cell Proliferation and Neuronal Differentiation AGING-US Brett, J. O., Renault, V. M., Rafalski, V. A., Webb, A. E., Brunet, A. 2011; 3 (2): 108-124


    In adult mammals, neural stem cells (NSCs) generate new neurons that are important for specific types of learning and memory. Controlling adult NSC number and function is fundamental for preserving the stem cell pool and ensuring proper levels of neurogenesis throughout life. Here we study the importance of the microRNA gene cluster miR-106b~25 (miR-106b, miR-93, and miR-25) in primary cultures of neural stem/progenitor cells (NSPCs) isolated from adult mice. We find that knocking down miR-25 decreases NSPC proliferation, whereas ectopically expressing miR-25 promotes NSPC proliferation. Expressing the entire miR-106b~25 cluster in NSPCs also increases their ability to generate new neurons. Interestingly, miR-25 has a number of potential target mRNAs involved in insulin/insulin-like growth factor-1 (IGF) signaling, a pathway implicated in aging. Furthermore, the regulatory region of miR-106b~25 is bound by FoxO3, a member of the FoxO family of transcription factors that maintains adult stem cells and extends lifespan downstream of insulin/IGF signaling. These results suggest that miR-106b~25 regulates NSPC function and is part of a network involving the insulin/IGF-FoxO pathway, which may have important implications for the homeostasis of the NSC pool during aging.

    View details for Web of Science ID 000288170400008

    View details for PubMedID 21386132

  • FoxO3 Regulates Neural Stem Cell Homeostasis CELL STEM CELL Renault, V. M., Rafalski, V. A., Morgan, A. A., Salih, D. A., Brett, J. O., Webb, A. E., Villeda, S. A., Thekkat, P. U., Guillerey, C., Denko, N. C., Palmer, T. D., Bufte, A. J., Brunet, A. 2009; 5 (5): 527-539


    In the nervous system, neural stem cells (NSCs) are necessary for the generation of new neurons and for cognitive function. Here we show that FoxO3, a member of a transcription factor family known to extend lifespan in invertebrates, regulates the NSC pool. We find that adult FoxO3(-/-) mice have fewer NSCs in vivo than wild-type counterparts. NSCs isolated from adult FoxO3(-/-) mice have decreased self-renewal and an impaired ability to generate different neural lineages. Identification of the FoxO3-dependent gene expression profile in NSCs suggests that FoxO3 regulates the NSC pool by inducing a program of genes that preserves quiescence, prevents premature differentiation, and controls oxygen metabolism. The ability of FoxO3 to prevent the premature depletion of NSCs might have important implications for counteracting brain aging in long-lived species.

    View details for DOI 10.1016/j.stem.2009.09.014

    View details for Web of Science ID 000272019500014

    View details for PubMedID 19896443

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