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    Andrew Brack, PhD

    TitleAssociate Professor
    SchoolUCSF School of Medicine
    DepartmentOrthopaedic Surgery
    Address35 Medical Center Way
    San Francisco CA 94143
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      Originally from Liverpool, England, Andrew graduated with a PhD in Molecular Biology and Biophysics from King’s College London. He did two postdoctoral fellowships, the first with Simon Hughes at King’s College London and the second with Tom Rando at Stanford University. Andrew started his own lab at the Center for Regenerative Medicine, MGH, Harvard University in 2008. In 2015 he moved to UCSF to begin the next phase of his lab's journey.

      Brack Lab's is focused on understanding the cellullar communication between the muscle stem cell and its environment to identify strategies that improve skeletal muscle regeneration and ameliorate sarcopenia.

      Quiescence and self-renewal
      Maintenance and reacquisition of quiescence are defining features of adult stem cells. We are studying the intrinsic and extrinsic factors that control quiescence and how they impinge on self-renewal and differentiation potential during muscle homeostasis, injury response and aging. Using a muscle stem cell specific mutant we demonstrated that Sprouty1 (Spry1), an RTK signaling inhibitor, is required for the reestablishment of quiescence in proliferating stem cells. We are presently identifying intrinsic and niche-derived signals that promote and retain stem cell potential.

      Stem cell niche
      The stem cell niche as originally conceptualized refers to the microenvironment that maintains ‘stemness’. The niche is a protector of stem cell number and function restraining proliferation and differentiation of stem cells and maintaining a quiescent phenotype. The satellite cell niche may be composed of different cell types. We are presently identifying the cell types and the essential signaling elements that compose the niche to retain stemness after injury and are deregulated during aging.

      Satellite cell heterogeneity
      It is apparent that adult stem cell populations are heterogeneous. Using a marker of proliferative history, based on retention of a fluorescent marker, we recently demonstrated that the adult satellite cell pool is composed of subsets of cells that are slowly dividing during ontogeny. Label retaining cells possess the properties of stem cells; in contrast, satellite cell subsets that diluted label functioned as progenitors. During aging a subset of functional label retaining cells are preserved. Current projects are deciphering whether heterogeneity is due to extrinsic influences, such as discrete niches, or cell intrinsic regulation, such as epigenetic and metabolic status.

      Aging is associated with a progressive decline in many tissues throughout the body. Skeletal muscle is no exception. We are studying the mechanisms that lead to a loss of stem cell number and function during aging.

      Brack Lab's Full Address is:
      Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research
      Department of Orthopaedic Surgery
      University of California, San Francisco
      35 Medical Center Way Box 0669
      San Francisco, CA 94143

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      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. Harper SC, Brack A, MacDonnell S, Franti M, Olwin BB, Bailey BA, Rudnicki MA, Houser SR. Is Growth Differentiation Factor 11 a Realistic Therapeutic for Aging-Dependent Muscle Defects? Circ Res. 2016 Apr 1; 118(7):1143-50. PMID: 27034276.
        View in: PubMed
      2. Brack AS, Muñoz-Cánoves P. The ins and outs of muscle stem cell aging. Skelet Muscle. 2015; 6:1. PMID: 26783424.
        View in: PubMed
      3. Eliazer S, Brack AS. Lost in Translation: Preserving Satellite Cell Function with Global Translational Control. Cell Stem Cell. 2016 Jan 7; 18(1):5-7. PMID: 26748748.
        View in: PubMed
      4. Kollu S, Abou-Khalil R, Shen C, Brack AS. The Spindle Assembly Checkpoint Safeguards Genomic Integrity of Skeletal Muscle Satellite Cells. Stem Cell Reports. 2015 Jun 9; 4(6):1061-74. PMID: 25960061; PMCID: PMC4471836.
      5. Brack AS. Pax7 is back. Skelet Muscle. 2014; 4(1):24. PMID: 25546147; PMCID: PMC4276024.
      6. Abraham J, Nuñez-Álvarez Y, Hettmer S, Carrió E, Chen HI, Nishijo K, Huang ET, Prajapati SI, Walker RL, Davis S, Rebeles J, Wiebush H, McCleish AT, Hampton ST, Bjornson CR, Brack AS, Wagers AJ, Rando TA, Capecchi MR, Marini FC, Ehler BR, Zarzabal LA, Goros MW, Michalek JE, Meltzer PS, Langenau DM, LeGallo RD, Mansoor A, Chen Y, Suelves M, Rubin BP, Keller C. Lineage of origin in rhabdomyosarcoma informs pharmacological response. Genes Dev. 2014 Jul 15; 28(14):1578-91. PMID: 25030697; PMCID: PMC4102765.
      7. Chakkalakal JV, Christensen J, Xiang W, Tierney MT, Boscolo FS, Sacco A, Brack AS. Early forming label-retaining muscle stem cells require p27kip1 for maintenance of the primitive state. Development. 2014 Apr; 141(8):1649-59. PMID: 24715455; PMCID: PMC3978835.
      8. Jung Y, Brack AS. Cellular mechanisms of somatic stem cell aging. Curr Top Dev Biol. 2014; 107:405-38. PMID: 24439814; PMCID: PMC3982593.
      9. Brack AS, Hochedlinger K. ISSCR 2013: back to Bean Town. Stem Cell Reports. 2013; 1(6):479-85. PMID: 25847520; PMCID: PMC3871383.
      10. Brack AS. Ageing of the heart reversed by youthful systemic factors! EMBO J. 2013 Aug 14; 32(16):2189-90. PMID: 23860129; PMCID: PMC3746199.
      11. Li Z, Gilbert JA, Zhang Y, Zhang M, Qiu Q, Ramanujan K, Shavlakadze T, Eash JK, Scaramozza A, Goddeeris MM, Kirsch DG, Campbell KP, Brack AS, Glass DJ. An HMGA2-IGF2BP2 axis regulates myoblast proliferation and myogenesis. Dev Cell. 2012 Dec 11; 23(6):1176-88. PMID: 23177649; PMCID: PMC3645921.
      12. Chakkalakal JV, Jones KM, Basson MA, Brack AS. The aged niche disrupts muscle stem cell quiescence. Nature. 2012 Oct 18; 490(7420):355-60. PMID: 23023126; PMCID: PMC3605795.
      13. Brack AS, Rando TA. Tissue-specific stem cells: lessons from the skeletal muscle satellite cell. Cell Stem Cell. 2012 May 4; 10(5):504-14. PMID: 22560074; PMCID: PMC3348769.
      14. Warren L, Manos PD, Ahfeldt T, Loh YH, Li H, Lau F, Ebina W, Mandal PK, Smith ZD, Meissner A, Daley GQ, Brack AS, Collins JJ, Cowan C, Schlaeger TM, Rossi DJ. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell. 2010 Nov 5; 7(5):618-30. PMID: 20888316; PMCID: PMC3656821.
      15. Abou-Khalil R, Brack AS. Muscle stem cells and reversible quiescence: the role of sprouty. Cell Cycle. 2010 Jul 1; 9(13):2575-80. PMID: 20581433.
        View in: PubMed
      16. Shea KL, Xiang W, LaPorta VS, Licht JD, Keller C, Basson MA, Brack AS. Sprouty1 regulates reversible quiescence of a self-renewing adult muscle stem cell pool during regeneration. Cell Stem Cell. 2010 Feb 5; 6(2):117-29. PMID: 20144785; PMCID: PMC2846417.
      17. Brack AS, Murphy-Seiler F, Hanifi J, Deka J, Eyckerman S, Keller C, Aguet M, Rando TA. BCL9 is an essential component of canonical Wnt signaling that mediates the differentiation of myogenic progenitors during muscle regeneration. Dev Biol. 2009 Nov 1; 335(1):93-105. PMID: 19699733; PMCID: PMC3259687.
      18. Brack A. Adult muscle stem cells avoid death and Paxes. Cell Stem Cell. 2009 Aug 7; 5(2):132-4. PMID: 19664985.
        View in: PubMed
      19. Chargé SB, Brack AS, Bayol SA, Hughes SM. MyoD- and nerve-dependent maintenance of MyoD expression in mature muscle fibres acts through the DRR/PRR element. BMC Dev Biol. 2008; 8:5. PMID: 18215268; PMCID: PMC2259323.
      20. Brack AS, Conboy IM, Conboy MJ, Shen J, Rando TA. A temporal switch from notch to Wnt signaling in muscle stem cells is necessary for normal adult myogenesis. Cell Stem Cell. 2008 Jan 10; 2(1):50-9. PMID: 18371421.
        View in: PubMed
      21. Brack AS, Conboy MJ, Roy S, Lee M, Kuo CJ, Keller C, Rando TA. Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science. 2007 Aug 10; 317(5839):807-10. PMID: 17690295.
        View in: PubMed
      22. Brack AS, Rando TA. Intrinsic changes and extrinsic influences of myogenic stem cell function during aging. Stem Cell Rev. 2007; 3(3):226-37. PMID: 17917136.
        View in: PubMed
      23. Brack AS, Bildsoe H, Hughes SM. Evidence that satellite cell decrement contributes to preferential decline in nuclear number from large fibres during murine age-related muscle atrophy. J Cell Sci. 2005 Oct 15; 118(Pt 20):4813-21. PMID: 16219688.
        View in: PubMed
      24. Bruusgaard JC, Brack AS, Hughes SM, Gundersen K. Muscle hypertrophy induced by the Ski protein: cyto-architecture and ultrastructure. Acta Physiol Scand. 2005 Oct; 185(2):141-9. PMID: 16168008.
        View in: PubMed
      25. Brack AS, Brandmeier BD, Ferguson RE, Criddle S, Dale RE, Irving M. Bifunctional rhodamine probes of Myosin regulatory light chain orientation in relaxed skeletal muscle fibers. Biophys J. 2004 Apr; 86(4):2329-41. PMID: 15041671; PMCID: PMC1304082.
      26. Ferguson RE, Sun YB, Mercier P, Brack AS, Sykes BD, Corrie JE, Trentham DR, Irving M. In situ orientations of protein domains: troponin C in skeletal muscle fibers. Mol Cell. 2003 Apr; 11(4):865-74. PMID: 12718873.
        View in: PubMed
      27. Chargé SB, Brack AS, Hughes SM. Aging-related satellite cell differentiation defect occurs prematurely after Ski-induced muscle hypertrophy. Am J Physiol Cell Physiol. 2002 Oct; 283(4):C1228-41. PMID: 12225986.
        View in: PubMed
      28. Rittner HL, Kaiser M, Brack A, Szweda LI, Goronzy JJ, Weyand CM. Tissue-destructive macrophages in giant cell arteritis. Circ Res. 1999 May 14; 84(9):1050-8. PMID: 10325242.
        View in: PubMed
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