Andrew Brack, Ph.D.
Associate Professor of Medicine, Harvard Medical School
In uninjured muscle, the rare satellite cells are in a functionally dormant, quiescent state. Upon an injury stimulus, these cells proliferate and their progeny will either differentiate to form new muscle fibers or undergo self renewal to replenish the stem cell pool.
We believe that the temporally coordinated cell fate decisions of the stem cell and its progeny are reliant on the communication between the local environment (the muscle stem cell niche) and the stem cell itself. We are using cre/lox gene recombination and genetic knock in technology to deconstruct the communication between the niche and the muscle stem cell to investigate the cell fate decision making process during regeneration. In the future we hope this will lead to strategies that improve stem cell based therapies targeting aging and muscle disease.
|FUNDING AND AWARDS|
|2011-||Muscular Dystrophy Association Research Award|
|2010-2012||Harvard Stem Cell Institute Seed Grant|
|2009-2012||Harvard Stem Cell Institute Junior Faculty Award|
|2009-2013||Ellison Medical Foundation Young Investigator Award|
For research opportunities please contact Dr. Andrew Brack.
1. Charge, S., Brack, A.S., Hughes, S. M. (2002) Aging-related satellite cell differentiation defect occurs prematurely after Ski-induced muscle hypertrophy. Am.J.Cell.Physiol. 283:C1228-C1241. PMID: 12225986
2. Ferguson, R.E., Sun, Y.B., Mercier, P., Brack, A.S., Sykes, B.D., Corrie, J.E., Trentham, D.R., Irving, M. (2003) In situ orientations of protein domains: troponin C in skeletal muscle fibers. Mol.Cell. 11:865-74. PMID: 12718873
3. Brack, A.S., Brandmeier, B.D., Ferguson, R.E., Criddle, S., Dale, R.E., Irving, M. (2004) Bifunctional rhodamine probe of myosin regulatory light chain orientation in relaxed single muscle fibres. Biophys.J. 2004 86: 2329-2341.
4. Brack, A.S., Bildsoe, H., Hughes, S.M. (2005) A satellite cell defect leads to a loss of myonuclei in murine age-related atrophy and is exacerbated in large muscle fibres. J.Cell Sci. 118: 4813-21.
5. Bruusgaard, J.C., Brack, A.S., Hughes, S.M., Gundersen, K. (2005) Muscle hypertrophy induced by the Ski protein: Cyto-architecture and ultrastructure. Acta.Physiol.Scand. 185: 141-9. PMID: 16168008
6. Brack, A.S., Conboy, M.J., Roy, S., Lee, M., Kuo, C., Rando, T.A. (2007) Elevated Wnt signaling during aging alters the fate of myogenic stem cells leading to increased fibrosis and impaired regeneration. Science. 317: 807-810.
7. Brack, A.S., Conboy, I.M., Conboy, M.J., Shen, J, and Rando, T.A. (2008) A temporal switch from Notch to Wnt is necessary for normal adult myogenesis. Cell Stem Cell. 2, 50-59. PMID: 18371421
8. Brack, A.S., Charge, S., Bayol, S., Hughes, S. M. (2008) MyoD and nerve-dependent maintenance of myoD expression in mature muscle fibres acts through the DRR/PRR element. BMC: Dev. Biol. (1):5 PMCID: PMC2259323
9. Brack, A.S., Murphy-Seiler, F., Hanifi, J., Deka, J., Eyckerman, S., Keller, C., Aguet, M., and Rando, T.A. (2009). BCL9 is an essential component of canonical Wnt signaling that mediates the differentiation of myogenic progenitors during muscle regeneration. Developmental biology 335(1): 93-105. PMID: 19699733
10. Shea, K.L, Xiang, W., LaPorta, V.S., Licht, J.D., Keller, C., Basson, M.A., Brack, A.S. (2010) Sprouty1 Regulates Reversible Quiescence of a Self-Renewing Adult Muscle Stem Cell Pool during Regeneration. Cell Stem Cell 6: 117-129. PMID: 20144785
11. Warren L, Manos PD, Ahfeldt T, Loh YH, Li H, Lau F, Ebina W, Mandal PK, Smith ZD, Meissner A, Daley GQ, Brack, A.S., 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. Epub 2010 Sep 30.
12. Chakkalakal, J., Jones, K., Basson, M., Brack, A.S., (2012). The aged niche disrupts muscle stem cell quiescence. Nature. 490: 355-360. PMCID: PMC3605795.
13. 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 A.S., Glass DJ. (2012). An HMGA2-IGF2BP2 axis regulates myoblast proliferation and myogenesis. Dev Cell. 11;23(6):1176-88.
14. Chakkalakal JV1, Christensen J, Xiang W, Tierney MT, Boscolo FS, Sacco A, Brack A.S. Early forming label-retaining muscle stem cells require p27kip1 for maintenance of the primitive state. Development. 2014; Apr141(8):1649-59. doi: 10.1242/dev.100842. PMID: 24715455.
Reviews, Chapters and Editorials.
1. Brack, A.S and Rando, T.A. (2007) Intrinsic changes and extrinsic influences of myogenic stem cell function during Aging. Stem Cell Rev. 3: 226-237.
2. Brack, A.S and Rando, T.A. (2008) Age-Dependent Changes in Skeletal Muscle Regeneration. Skeletal Muscle Repair and Regeneration. 359-374.
3. Brack, A.S. (2009) Adult muscle stem cells avoid death and Paxes. Cell Stem cell 5(2): 132-134.
4. Abou-Khalil, R and Brack, A.S. (2010) Muscle Stem Cells and Reversible Quiescence; The role of Sprouty. Cell Cycle. 9:13; 1-6.
5. Brack A.S., Rando TA. Tissue-specific stem cells: lessons from the skeletal muscle satellite cell. Cell Stem Cell. 2012 May 4;10(5):504-14.
6. Chakkalakal JV, Brack A.S., (2012). Extrinsic regulation of satellite cell function and muscle regeneration Capacity during Aging. J Stem Cell Res Ther S11:001.
7. Brack A.S. Ageing of the heart reversed by youthful systemic factors!. EMBO J.2013 Aug 14;32(16):2189-90. doi:10.1038/emboj.2013.162. Epub 2013 Jul 16. PMCID: PMC3746199. (PDF)
8. Brack A.S., Hochedlinger K. ISSCR 2013: Back to the Bean Town. Stem Cell Reports. 2013 December 17; 1(6): 479–485. Published online 2013 December 17. doi: 10.1016/j.stemcr.2013.12.004. PMCID: PMC3871383.
9. Jung Y, Brack AS. Cellular mechanisms of somatic stem cell aging. Curr Top Dev Biol. 2014;107:405-38. doi: 10.1016/B978-0-12-416022-4.00014-7. PMID: 24439814.