Saul Villeda, PhD

Title(s)Assistant Professor, Anatomy
SchoolSchool of Medicine
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    Collapse Biography 
    Collapse Education and Training
    Stanford UniversityPh.D.2011Neuroscience
    University of California, Los AngelesB.S.2004Physiological Science
    Collapse Awards and Honors
    2015Glenn Award for Research on the Biological Mechanisms of Aging
    2012NIH Director's Early Independence Award (DP5)

    Collapse Overview 
    Collapse Overview
    The ability to reverse aging in the brain may enable us to sidestep the effects of aging that promote vulnerability to neurodegenerative diseases, providing a unique and unexplored therapeutic approach. We have recently shown that systemic manipulations such as heterochronic parabiosis or young blood administration can partially reverse age-related impairments in regenerative, synaptic and cognitive functions in the aged brain. Interestingly, heterochronic parabiosis studies revealed an age-dependent bi-directionality in the influence of the systemic environment indicating pro-youthful factors in young blood elicit rejuvenation while pro-aging factors in old blood drive pre-mature aging. Therefore, targeting pro-aging factors in old blood may provide an alternative approach to rejuvenate aging phenotypes. Our lab is interested in understanding what drives regenerative and cognitive impairments in the aging brain, and how the effects of aging can be reversed in the old brain. Ultimately, our goal is to elucidate cellular and molecular mechanisms that promote brain rejuvenation as a means by which to combat age-related neurodegeneration and cognitive dysfunction.

    Collapse Research 
    Collapse Research Activities and Funding
    Role of O-GlcNAcylation in Regulating Neurodegeneration in Aging and Alzheimer?s Disease
    NIH/NIA RF1AG062357Sep 30, 2018 - Jun 30, 2023
    Role: Principal Investigator
    Investigating the pro-aging role of B2M and MHC molecules on regenerative and cognitive function in the brain
    NIH/NIA R01AG055797Mar 1, 2017 - Feb 28, 2022
    Role: Principal Investigator
    Mechanisms of brain rejuvenation
    NIH/NIA R01AG053382Aug 15, 2016 - Apr 30, 2021
    Role: Principal Investigator
    Regulation of Neurogenesis and Cognition by Systemic Age-Related Immune Factors
    NIH DP5OD012178Sep 15, 2012 - Aug 31, 2017
    Role: Principal Investigator
    Regulation of Neural Stem Cells by Changes in the Aging Systemic Environment
    NIH/NIA F31AG034045Mar 13, 2009 - Mar 12, 2012
    Role: Principal Investigator

    Collapse ORNG Applications 
    Collapse Websites
    Collapse In The News

    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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    1. Schroer AB, Horowitz AM, Villeda SA. Platelets Give a Running Start to Adult Hippocampal Neurogenesis. Stem Cell Reports. 2019 Apr 09; 12(4):643-646. PMID: 30951653.
      View in: PubMed
    2. Bieri G, Lucin KM, O'Brien CE, Zhang H, Villeda SA, Wyss-Coray T. Proteolytic cleavage of Beclin 1 exacerbates neurodegeneration. Mol Neurodegener. 2018 12 29; 13(1):68. PMID: 30594228.
      View in: PubMed
    3. Gontier G, Iyer M, Shea JM, Bieri G, Wheatley EG, Ramalho-Santos M, Villeda SA. Tet2 Rescues Age-Related Regenerative Decline and Enhances Cognitive Function in the Adult Mouse Brain. Cell Rep. 2018 Feb 20; 22(8):1974-1981. PMID: 29466726.
      View in: PubMed
    4. Smith LK, White CW, Villeda SA. The systemic environment: at the interface of aging and adult neurogenesis. Cell Tissue Res. 2018 01; 371(1):105-113. PMID: 29124393.
      View in: PubMed
    5. Deczkowska A, Matcovitch-Natan O, Tsitsou-Kampeli A, Ben-Hamo S, Dvir-Szternfeld R, Spinrad A, Singer O, David E, Winter DR, Smith LK, Kertser A, Baruch K, Rosenzweig N, Terem A, Prinz M, Villeda S, Citri A, Amit I, Schwartz M. Mef2C restrains microglial inflammatory response and is lost in brain ageing in an IFN-I-dependent manner. Nat Commun. 2017 09 28; 8(1):717. PMID: 28959042.
      View in: PubMed
    6. Horowitz AM, Villeda SA. Therapeutic potential of systemic brain rejuvenation strategies for neurodegenerative disease. F1000Res. 2017; 6:1291. PMID: 28815019.
      View in: PubMed
    7. Fan X, Wheatley EG, Villeda SA. Mechanisms of Hippocampal Aging and the Potential for Rejuvenation. Annu Rev Neurosci. 2017 07 25; 40:251-272. PMID: 28441118.
      View in: PubMed
    8. Middeldorp J, Lehallier B, Villeda SA, Miedema SS, Evans E, Czirr E, Zhang H, Luo J, Stan T, Mosher KI, Masliah E, Wyss-Coray T. Preclinical Assessment of Young Blood Plasma for Alzheimer Disease. JAMA Neurol. 2016 Nov 01; 73(11):1325-1333. PMID: 27598869.
      View in: PubMed
    9. Zhang Y, Roth TL, Gray EE, Chen H, Rodda LB, Liang Y, Ventura P, Villeda S, Crocker PR, Cyster JG. Migratory and adhesive cues controlling innate-like lymphocyte surveillance of the pathogen-exposed surface of the lymph node. Elife. 2016 08 03; 5. PMID: 27487469.
      View in: PubMed
    10. Udeochu JC, Shea JM, Villeda SA. Microglia communication: Parallels between aging and Alzheimer's disease. Clin Exp Neuroimmunol. 2016 May; 7(2):114-125. PMID: 27840659.
      View in: PubMed
    11. Armanios M, de Cabo R, Mannick J, Partridge L, van Deursen J, Villeda S. Translational strategies in aging and age-related disease. Nat Med. 2015 Dec; 21(12):1395-9. PMID: 26646495.
      View in: PubMed
    12. Gontier G, Lin K, Villeda SA. Fat Chance for Neural Stem Cells in Alzheimer's Disease. Cell Stem Cell. 2015 Oct 01; 17(4):373-4. PMID: 26431177.
      View in: PubMed
    13. Smith LK, He Y, Park JS, Bieri G, Snethlage CE, Lin K, Gontier G, Wabl R, Plambeck KE, Udeochu J, Wheatley EG, Bouchard J, Eggel A, Narasimha R, Grant JL, Luo J, Wyss-Coray T, Villeda SA. ß2-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis. Nat Med. 2015 Aug; 21(8):932-7. PMID: 26147761; PMCID: PMC4529371.
    14. Bouchard J, Villeda SA. Aging and brain rejuvenation as systemic events. J Neurochem. 2015 Jan; 132(1):5-19. PMID: 25327899; PMCID: PMC4301186.
    15. He Y, Zhang H, Yung A, Villeda SA, Jaeger PA, Olayiwola O, Fainberg N, Wyss-Coray T. ALK5-dependent TGF-ß signaling is a major determinant of late-stage adult neurogenesis. Nat Neurosci. 2014 Jul; 17(7):943-52. PMID: 24859199; PMCID: PMC4096284.
    16. Villeda SA, Plambeck KE, Middeldorp J, Castellano JM, Mosher KI, Luo J, Smith LK, Bieri G, Lin K, Berdnik D, Wabl R, Udeochu J, Wheatley EG, Zou B, Simmons DA, Xie XS, Longo FM, Wyss-Coray T. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat Med. 2014 Jun; 20(6):659-63. PMID: 24793238; PMCID: PMC4224436.
    17. Luo J, Nguyen A, Villeda S, Zhang H, Ding Z, Lindsey D, Bieri G, Castellano JM, Beaupre GS, Wyss-Coray T. Long-term cognitive impairments and pathological alterations in a mouse model of repetitive mild traumatic brain injury. Front Neurol. 2014; 5:12. PMID: 24550885; PMCID: PMC3912443.
    18. Luo J, Elwood F, Britschgi M, Villeda S, Zhang H, Ding Z, Zhu L, Alabsi H, Getachew R, Narasimhan R, Wabl R, Fainberg N, James ML, Wong G, Relton J, Gambhir SS, Pollard JW, Wyss-Coray T. Colony-stimulating factor 1 receptor (CSF1R) signaling in injured neurons facilitates protection and survival. J Exp Med. 2013 Jan 14; 210(1):157-72. PMID: 23296467; PMCID: PMC3549715.
    19. Villeda SA, Wyss-Coray T. The circulatory systemic environment as a modulator of neurogenesis and brain aging. Autoimmun Rev. 2013 Apr; 12(6):674-7. PMID: 23201925.
      View in: PubMed
    20. Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G, Stan TM, Fainberg N, Ding Z, Eggel A, Lucin KM, Czirr E, Park JS, Couillard-Després S, Aigner L, Li G, Peskind ER, Kaye JA, Quinn JF, Galasko DR, Xie XS, Rando TA, Wyss-Coray T. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature. 2011 Aug 31; 477(7362):90-4. PMID: 21886162; PMCID: PMC3170097.
    21. Moriyama M, Fukuhara T, Britschgi M, He Y, Narasimhan R, Villeda S, Molina H, Huber BT, Holers M, Wyss-Coray T. Complement receptor 2 is expressed in neural progenitor cells and regulates adult hippocampal neurogenesis. J Neurosci. 2011 Mar 16; 31(11):3981-9. PMID: 21411641; PMCID: PMC3071463.
    22. 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. FoxO3 regulates neural stem cell homeostasis. Cell Stem Cell. 2009 Nov 06; 5(5):527-39. PMID: 19896443; PMCID: PMC2775802.
    23. Villeda S, Wyss-Coray T. Microglia--a wrench in the running wheel? Neuron. 2008 Aug 28; 59(4):527-9. PMID: 18760689.
      View in: PubMed
    24. Kubasak MD, Brooks R, Chen S, Villeda SA, Phelps PE. Developmental distribution of reelin-positive cells and their secreted product in the rodent spinal cord. J Comp Neurol. 2004 Jan 06; 468(2):165-78. PMID: 14648677.
      View in: PubMed