Joe V. Chakkalakal, PhD

Associate Professor in the Department of Orthopaedic Surgery and Cell Biology
Duke Orthopaedics, Cellular, Developmental, and Genome Laboratories

The Chakkalakal Lab

The Chakkalakal laboratory utilizes murine models, injury paradigms, cell culture systems, imaging techniques, physiological assessment, and gene expression analysis to determine how specific cell populations and molecules of interest affect neuromuscular development, maintenance, and regeneration.

Selected Publications

Muscle-specific functional deficits and lifelong fibrosis in response to pediatric radiotherapy and tumor elimination. Kallenbach JG, Bachman JF, Paris ND, Blanc RS, O'Connor T, Furati E, Hernady E, Johnston CJ, Williams JP, Chakkalakal JV. J Cachexia Sarcopenia Muscle. 2022 Jan 8. doi: 10.1002/jcsm.12902.

Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging. Larouche JA, Mohiuddin M, Choi JJ, Ulintz PJ, Fraczek P, Sabin K, Pitchiaya S, Kurpiers SJ, Castor-Macias J, Liu W, Hastings RL, Brown LA, Markworth JF, De Silva K, Levi B, Merajver SD, Valdez G, Chakkalakal JV, Jang YC, Brooks SV, Aguilar CA. Elife. 2021 Jul 29;10:e66749. doi: 10.7554/eLife.66749.

Increased myocellular lipid and IGFBP-3 expression in a pre-clinical model of pancreatic cancer-related skeletal muscle wasting. Cole CL, Bachman JF, Ye J, Murphy J, Gerber SA, Beck CA, Boyce BF, Muthukrishnan G, Chakkalakal JV, Schwarz EM, Linehan D. J Cachexia Sarcopenia Muscle. 2021 Jun;12(3):731-745. doi: 10.1002/jcsm.12699.

Insights into muscle stem cell dynamics during postnatal development. Bachman JF, Chakkalakal JV. FEBS J. 2021 Apr 2. doi: 10.1111/febs.15856. Radiation-Induced Damage to Prepubertal Pax7+ Skeletal Muscle Stem Cells Drives Lifelong Deficits in Myofiber Size and Nuclear Number. Bachman JF, Blanc RS, Paris ND, Kallenbach JG, Johnston CJ, Hernady E, Williams JP, Chakkalakal JV. iScience. 2020 Nov 2;23(11):101760. doi: 10.1016/j.isci.2020.101760.

Chemoradiation impairs myofiber hypertrophic growth in a pediatric tumor model. Paris ND, Kallenbach JG, Bachman JF, Blanc RS, Johnston CJ, Hernady E, Williams JP, Chakkalakal JV. Sci Rep. 2020 Nov 11;10(1):19501. doi: 10.1038/s41598-020-75913-w.

Inhibition of inflammatory CCR2 signaling promotes aged muscle regeneration and strength recovery after injury. Blanc RS, Kallenbach JG, Bachman JF, Mitchell A, Paris ND, Chakkalakal JV. Nat Commun. 2020 Aug 20;11(1):4167. doi: 10.1038/s41467-020-17620-8.

TNF Receptor-Associated Factor 6 Mediates TNFα-Induced Skeletal Muscle Atrophy in Mice During Aging. Li J, Yi X, Yao Z, Chakkalakal JV, Xing L, Boyce BF. J Bone Miner Res. 2020 Aug;35(8):1535-1548. doi: 10.1002/jbmr.4021.

Prostate tumor-derived GDF11 accelerates androgen deprivation therapy-induced sarcopenia. Pan C, Jaiswal Agrawal N, Zulia Y, Singh S, Sha K, Mohler JL, Eng KH, Chakkalakal JV, Krolewski JJ, Nastiuk KL. JCI Insight. 2020 Mar 26;5(6): e127018. doi: 10.1172/jci.insight.127018.

4-Aminopyridine attenuates muscle atrophy after sciatic nerve crush injury in mice. Yue L, Talukder MAH, Gurjar A, Lee JI, Noble M, Dirksen RT, Chakkalakal J, Elfar JC. Muscle Nerve. 2019 Aug;60(2):192-201. doi: 10.1002/mus.26516.

Selective Sexual Dimorphisms in Musculoskeletal and Cardiopulmonary Pathologic Manifestations and Mortality Incidence in the Tumor Necrosis Factor-Transgenic Mouse Model of Rheumatoid Arthritis. Bell RD, Wu EK, Rudmann CA, Forney M, Kaiser CRW, Wood RW, Chakkalakal JV, Paris ND, Klose A, Xiao GQ, Rangel-Moreno J, Garcia-Hernandez ML, Ritchlin CT, Schwarz EM, Rahimi H. Arthritis Rheumatol. 2019 Sep;71(9):1512-1523. doi: 10.1002/art.40903.

Prepubertal skeletal muscle growth requires Pax7-expressing satellite cell-derived myonuclear contribution. Bachman JF, Klose A, Liu W, Paris ND, Blanc RS, Schmalz M, Knapp E, Chakkalakal JV. Development. 2018 Oct 25;145(20): dev167197. doi: 10.1242/dev.167197.

Castration induces satellite cell activation that contributes to skeletal muscle maintenance. Klose A, Liu W, Paris ND, Forman S, Krolewski JJ, Nastiuk KL, Chakkalakal JV. JCSM Rapid Commun. 2018;1(1): e00040.

The Composition, Development, and Regeneration of Neuromuscular Junctions. Liu W, Chakkalakal JV. Curr Top Dev Biol. 2018; 126:99-124. doi: 10.1016/bs.ctdb.2017.08.005.

Research priorities in cancer cachexia: The University of Rochester Cancer Center NCI Community Oncology Research Program Research Base Symposium on Cancer Cachexia and Sarcopenia. Dunne RF, Mustian KM, Garcia JM, Dale W, Hayward R, Roussel B, Buschmann MM, Caan BJ, Cole CL, Fleming FJ, Chakkalakal JV, Linehan DC, Hezel AF, Mohile SG. Curr Opin Support Palliat Care. 2017 Dec;11(4):278-286. doi: 10.1097/SPC.0000000000000301.

Loss of adult skeletal muscle stem cells drives age-related neuromuscular junction degeneration. Liu W, Klose A, Forman S, Paris ND, Wei-LaPierre L, Cortés-Lopéz M, Tan A, Flaherty M, Miura P, Dirksen RT, Chakkalakal JV. Elife. 2017 Jun 6;6: e26464. doi: 10.7554/eLife.26464.

Smad4 restricts differentiation to promote expansion of satellite cell derived progenitors during skeletal muscle regeneration. Paris ND, Soroka A, Klose A, Liu W, Chakkalakal JV. Elife. 2016 Nov 18;5: e19484. doi: 10.7554/eLife.19484.

TGFβ Superfamily Members Mediate Androgen Deprivation Therapy-Induced Obese Frailty in Male Mice. Pan C, Singh S, Sahasrabudhe DM, Chakkalakal JV, Krolewski JJ, Nastiuk KL. Endocrinology. 2016 Nov;157(11):4461-4472. doi: 10.1210/en.2016-1580. Epub 2016 Sep 9.

Addressing the Symptoms or Fixing the Problem? Developing Countermeasures against Normal Tissue Radiation Injury. Williams JP, Calvi L, Chakkalakal JV, Finkelstein JN, O'Banion MK, Puzas E. Radiat Res. 2016 Jul;186(1):1-16. doi: 10.1667/RR14473.1. Epub 2016 Jun 22.

Inducible depletion of adult skeletal muscle stem cells impairs the regeneration of neuromuscular junctions. Liu W, Wei-LaPierre L, Klose A, Dirksen RT, Chakkalakal JV. Elife. 2015 Aug 27;4: e09221. doi: 10.7554/eLife.09221.

Early forming label-retaining muscle stem cells require p27kip1 for maintenance of the primitive state. Chakkalakal JV, Christensen J, Xiang W, Tierney MT, Boscolo FS, Sacco A, Brack AS. Development. 2014 Apr;141(8):1649-59. doi: 10.1242/dev.100842.

The aged niche disrupts muscle stem cell quiescence. Chakkalakal JV, Jones KM, Basson MA, Brack AS. Nature. 2012 Oct 18;490(7420):355-60. doi: 10.1038/nature11438.

Extrinsic Regulation of Satellite Cell Function and Muscle Regeneration Capacity during Aging. Chakkalakal J, Brack A. J Stem Cell Res Ther. 2012 Sep 26; Suppl 11:001. doi: 10.4172/2157-7633.S11-001.

Selected Grants

  • Cellular basis for radiation-induced acceleration of sarcopenia in juvenile cancer survivors (Principal Investigator), awarded by National Institutes of Health, 2017-2022
  • Targeting p21 to stimulate irradiated muscle stem cell function and muscle regeneration (F31) (Mentor), awarded by National Institutes of Health, 2019-2021
  • Interrelationships between age-related skeletal muscle stem cell and NMJ decline (Principal Investigator), awarded by National Institutes of Health, 2015-2020
  • A requirement for skeletal muscle stem cells in the regeneration of aged and injured neuromuscular junctions (Training Grant) (Mentor), awarded by New York State Stem Cell Science program, 2015-2016
  • Cellular basis for androgen deprivation therapy-induced acceleration of sarcopenia (Principal Investigator), awarded by Congressionally Directed Medical Research Program, 2014-2017