Andrew Brack, PhD

Associate Professor
Department of Orthopaedic Surgery
+1 415 476-3979

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
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

Websites

Publications: 

Is Growth Differentiation Factor 11 a Realistic Therapeutic for Aging-Dependent Muscle Defects?

Circulation research

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

Brack AS, Muñoz-Cánoves P

GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration.

Cell metabolism

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

Pax7 is back.

Skeletal muscle

Brack AS

Lineage of origin in rhabdomyosarcoma informs pharmacological response.

Genes & development

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

Early forming label-retaining muscle stem cells require p27kip1 for maintenance of the primitive state.

Development (Cambridge, England)

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

Jung Y, Brack AS

ISSCR 2013: back to Bean Town.

Stem cell reports

Brack AS, Hochedlinger K

An HMGA2-IGF2BP2 axis regulates myoblast proliferation and myogenesis.

Developmental cell

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

Chakkalakal JV, Jones KM, Basson MA, Brack AS

Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA.

Cell stem cell

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.)

Abou-Khalil R, Brack AS

Sprouty1 regulates reversible quiescence of a self-renewing adult muscle stem cell pool during regeneration.

Cell stem cell

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

Brack AS, Murphy-Seiler F, Hanifi J, Deka J, Eyckerman S, Keller C, Aguet M, Rando TA

Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis.

Science (New York, N.Y.)

Brack AS, Conboy MJ, Roy S, Lee M, Kuo CJ, Keller C, Rando TA

Muscle hypertrophy induced by the Ski protein: cyto-architecture and ultrastructure.

Acta physiologica Scandinavica

Bruusgaard JC, Brack AS, Hughes SM, Gundersen K

Bifunctional rhodamine probes of Myosin regulatory light chain orientation in relaxed skeletal muscle fibers.

Biophysical journal

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

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

Chargé SB, Brack AS, Hughes SM

Tissue-destructive macrophages in giant cell arteritis.

Circulation research

Rittner HL, Kaiser M, Brack A, Szweda LI, Goronzy JJ, Weyand CM