Andrew Brack, PhD
Professor
Orthopaedic Surgery
School of Medicine

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 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

• Lineage Tracing Reveals a Subset of Reserve Muscle Stem Cells Capable of Clonal Expansion under Stress.
  Cell stem cell 2019 Scaramozza A, Park D, Kollu S, Beerman I, Sun X, Rossi DJ, Lin CP, Scadden DT, Crist C, Brack AS
• Thermal stress induces glycolytic beige fat formation via a myogenic state.
  Nature 2018 Chen Y, Ikeda K, Yoneshiro T, Scaramozza A, Tajima K, Wang Q, Kim K, Shinoda K, Sponton CH, Brown Z, Brack A, Kajimura S
• Inferring cell state by quantitative motility analysis reveals a dynamic state system and broken detailed balance.
  PLoS computational biology 2018 Kimmel JC, Chang AY, Brack AS, Marshall WF
• Muscle Stem Cells and Aging.
  Current topics in developmental biology 2017 Hwang AB, Brack AS
• Stem cells: Cause and consequence in aged-muscle decline.
  Nature 2016 Eliazer S, Brack AS
• Is Growth Differentiation Factor 11 a Realistic Therapeutic for Aging-Dependent Muscle Defects?
  Circulation research 2016 Harper SC, Brack A, MacDonnell S, Franti M, Olwin BB, Bailey BA, Rudnicki MA, Houser SR
• The ins and outs of muscle stem cell aging.
  Skeletal muscle 2016 Brack AS, Muñoz-Cánoves P
• Lost in Translation: Preserving Satellite Cell Function with Global Translational Control.
  Cell stem cell 2016 Eliazer S, Brack AS
• GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration.
  Cell metabolism 2015 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, …
• The Spindle Assembly Checkpoint Safeguards Genomic Integrity of Skeletal Muscle Satellite Cells.
  Stem cell reports 2015 Kollu S, Abou-Khalil R, Shen C, Brack AS
• Pax7 is back.
  Skeletal muscle 2014 Brack AS
• Lineage of origin in rhabdomyosarcoma informs pharmacological response.
  Genes & development 2014 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 …
• Early forming label-retaining muscle stem cells require p27kip1 for maintenance of the primitive state.
  Development (Cambridge, England) 2014 Chakkalakal JV, Christensen J, Xiang W, Tierney MT, Boscolo FS, Sacco A, Brack AS
• Cellular mechanisms of somatic stem cell aging.
  Current topics in developmental biology 2014 Jung Y, Brack AS
• ISSCR 2013: back to Bean Town.
  Stem cell reports 2013 Brack AS, Hochedlinger K
• Ageing of the heart reversed by youthful systemic factors!
  The EMBO journal 2013 Brack AS
• An HMGA2-IGF2BP2 Axis Regulates Myoblast Proliferation and Myogenesis.
  Developmental Cell 2013 Zhizhong Li, Jason A. Gilbert, Yunyu Zhang, Minsi Zhang, Qiong Qiu, Krishnan Ramanujan, Tea Shavlakadze, John K. Eash, Annarita Scaramozza, Matthew M. Goddeeris, David G. Kirsch, Kevin P. Campbell, …
• An HMGA2-IGF2BP2 axis regulates myoblast proliferation and myogenesis.
  Developmental cell 2012 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
• The aged niche disrupts muscle stem cell quiescence.
  Nature 2012 Chakkalakal JV, Jones KM, Basson MA, Brack AS
• Tissue-specific stem cells: lessons from the skeletal muscle satellite cell.
  Cell stem cell 2012 Brack AS, Rando TA
• Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA.
  Cell stem cell 2010 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
• Muscle stem cells and reversible quiescence: the role of sprouty.
  Cell cycle (Georgetown, Tex.) 2010 Abou-Khalil R, Brack AS
• Sprouty1 regulates reversible quiescence of a self-renewing adult muscle stem cell pool during regeneration.
  Cell stem cell 2010 Shea KL, Xiang W, LaPorta VS, Licht JD, Keller C, Basson MA, Brack AS
• BCL9 is an essential component of canonical Wnt signaling that mediates the differentiation of myogenic progenitors during muscle regeneration.
  Developmental biology 2009 Brack AS, Murphy-Seiler F, Hanifi J, Deka J, Eyckerman S, Keller C, Aguet M, Rando TA
• Adult muscle stem cells avoid death and Paxes.
  Cell stem cell 2009 Brack A
• MyoD- and nerve-dependent maintenance of MyoD expression in mature muscle fibres acts through the DRR/PRR element.
  BMC developmental biology 2008 Chargé SB, Brack AS, Bayol SA, Hughes SM
• A temporal switch from notch to Wnt signaling in muscle stem cells is necessary for normal adult myogenesis.
  Cell stem cell 2008 Brack AS, Conboy IM, Conboy MJ, Shen J, Rando TA
• Age-Dependent Changes in Skeletal MuscleRegeneration.
  Skeletal Muscle Repair and Regeneration 2008 Andrew S. Brack, Thomas A. Rando
• Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis.
  Science (New York, N.Y.) 2007 Brack AS, Conboy MJ, Roy S, Lee M, Kuo CJ, Keller C, Rando TA
• Intrinsic changes and extrinsic influences of myogenic stem cell function during aging.
  Stem cell reviews 2007 Brack AS, Rando TA
• Evidence that satellite cell decrement contributes to preferential decline in nuclear number from large fibres during murine age-related muscle atrophy.
  Journal of cell science 2005 Brack AS, Bildsoe H, Hughes SM
• Muscle hypertrophy induced by the Ski protein: cyto-architecture and ultrastructure.
  Acta physiologica Scandinavica 2005 Bruusgaard JC, Brack AS, Hughes SM, Gundersen K
• Bifunctional rhodamine probes of Myosin regulatory light chain orientation in relaxed skeletal muscle fibers.
  Biophysical journal 2004 Brack AS, Brandmeier BD, Ferguson RE, Criddle S, Dale RE, Irving M
• In situ orientations of protein domains: troponin C in skeletal muscle fibers.
  Molecular cell 2003 Ferguson RE, Sun YB, Mercier P, Brack AS, Sykes BD, Corrie JE, Trentham DR, Irving M
• Aging-related satellite cell differentiation defect occurs prematurely after Ski-induced muscle hypertrophy.
  American journal of physiology. Cell physiology 2002 Chargé SB, Brack AS, Hughes SM
• Tissue-destructive macrophages in giant cell arteritis.
  Circulation research 1999 Rittner HL, Kaiser M, Brack A, Szweda LI, Goronzy JJ, Weyand CM