Andrew Brack, PhD

Title(s)Associate Professor, Orthopaedic Surgery
SchoolSchool of Medicine
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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

    Collapse Research 
    Collapse Research Activities and Funding
    Niche Regulation of Muscle Stem Cells
    NIH/NIAMS R01AR076252Aug 1, 2019 - May 31, 2024
    Role: Principal Investigator
    Single cell activation dynamics as a predictor and regulator of aged MuSC dysfunction.
    NIH/NIA R21AG063416Mar 15, 2019 - Jan 31, 2021
    Role: Principal Investigator
    Quiescence of Muscle Stem Cells During Growth and Repair
    NIH/NIAMS R01AR061002Apr 1, 2012 - Mar 31, 2017
    Role: Principal Investigator
    Muscle stem cell heterogeneity
    NIH/NIAMS R56AR060868Sep 21, 2011 - Aug 31, 2019
    Role: Principal Investigator
    Muscle Satellite Cell Pool During Aging
    NIH/NIAMS R01AR060868Sep 21, 2011 - Jul 31, 2016
    Role: Principal Investigator

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    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.
    List All   |   Timeline
    1. Kimmel J, Brack A, Marshall W. Deep convolutional and recurrent neural networks for cell motility discrimination and prediction. IEEE/ACM Trans Comput Biol Bioinform. 2019 Jun 27. PMID: 31251191.
      View in: PubMed
    2. Scaramozza A, Park D, Kollu S, Beerman I, Sun X, Rossi DJ, Lin CP, Scadden DT, Crist C, Brack AS. Lineage Tracing Reveals a Subset of Reserve Muscle Stem Cells Capable of Clonal Expansion under Stress. Cell Stem Cell. 2019 Jun 06; 24(6):944-957.e5. PMID: 31006621.
      View in: PubMed
    3. Chen Y, Ikeda K, Yoneshiro T, Scaramozza A, Tajima K, Wang Q, Kim K, Shinoda K, Sponton CH, Brown Z, Brack A, Kajimura S. Thermal stress induces glycolytic beige fat formation via a myogenic state. Nature. 2019 01; 565(7738):180-185. PMID: 30568302.
      View in: PubMed
    4. Kimmel JC, Chang AY, Brack AS, Marshall WF. Inferring cell state by quantitative motility analysis reveals a dynamic state system and broken detailed balance. PLoS Comput Biol. 2018 01; 14(1):e1005927. PMID: 29338005.
      View in: PubMed
    5. Hwang AB, Brack AS. Muscle Stem Cells and Aging. Curr Top Dev Biol. 2018; 126:299-322. PMID: 29305003.
      View in: PubMed
    6. Eliazer S, Brack AS. Stem cells: Cause and consequence in aged-muscle decline. Nature. 2016 12 15; 540(7633):349-350. PMID: 27919069.
      View in: PubMed
    7. 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 01; 118(7):1143-50; discussion 1150. PMID: 27034276; PMCID: PMC4829942 [Available on 04/01/17].
    8. Brack AS, Muñoz-Cánoves P. The ins and outs of muscle stem cell aging. Skelet Muscle. 2016; 6:1. PMID: 26783424; PMCID: PMC4716636.
    9. Eliazer S, Brack AS. Lost in Translation: Preserving Satellite Cell Function with Global Translational Control. Cell Stem Cell. 2016 Jan 07; 18(1):5-7. PMID: 26748748.
      View in: PubMed
    10. Egerman MA, Cadena SM, Gilbert JA, Meyer A, Nelson HN, Swalley SE, Mallozzi C, Jacobi C, Jennings LL, Clay I, Laurent G, Ma S, Brachat S, Lach-Trifilieff E, Shavlakadze T, Trendelenburg AU, Brack AS, Glass DJ. GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration. Cell Metab. 2015 Jul 07; 22(1):164-74. PMID: 26001423; PMCID: PMC4497834.
    11. 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 09; 4(6):1061-74. PMID: 25960061; PMCID: PMC4471836.
    12. Brack AS. Pax7 is back. Skelet Muscle. 2014; 4(1):24. PMID: 25546147; PMCID: PMC4276024.
    13. 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.
    14. 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.
    15. Jung Y, Brack AS. Cellular mechanisms of somatic stem cell aging. Curr Top Dev Biol. 2014; 107:405-38. PMID: 24439814; PMCID: PMC3982593.
    16. Brack AS, Hochedlinger K. ISSCR 2013: back to Bean Town. Stem Cell Reports. 2013; 1(6):479-85. PMID: 25847520; PMCID: PMC3871383.
    17. Brack AS. Ageing of the heart reversed by youthful systemic factors! EMBO J. 2013 Aug 14; 32(16):2189-90. PMID: 23860129; PMCID: PMC3746199.
    18. 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.
    19. 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.
      View in: PubMed
    20. Brack AS, Rando TA. Tissue-specific stem cells: lessons from the skeletal muscle satellite cell. Cell Stem Cell. 2012 May 04; 10(5):504-14. PMID: 22560074; PMCID: PMC3348769.
    21. 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 05; 7(5):618-30. PMID: 20888316; PMCID: PMC3656821.
    22. Abou-Khalil R, Brack AS. Muscle stem cells and reversible quiescence: the role of sprouty. Cell Cycle. 2010 Jul 01; 9(13):2575-80. PMID: 20581433.
      View in: PubMed
    23. 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 05; 6(2):117-29. PMID: 20144785; PMCID: PMC2846417.
    24. 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 01; 335(1):93-105. PMID: 19699733; PMCID: PMC3259687.
    25. Brack A. Adult muscle stem cells avoid death and Paxes. Cell Stem Cell. 2009 Aug 07; 5(2):132-4. PMID: 19664985.
      View in: PubMed
    26. 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 Jan 23; 8:5. PMID: 18215268; PMCID: PMC2259323.
    27. 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
    28. 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
    29. 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
    30. 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
    31. 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
    32. 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.
    33. 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
    34. 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
    35. 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