Associate Professor in the Department of Orthopaedic Surgery and Cell Biology
Duke Orthopaedics, Cellular, Developmental, and Genome Laboratories
joe.chakkalakal@duke.edu
Labsite: The Chakkalakal Lab
The Chakkalakal laboratory studies the cellular and molecular mechanisms that contribute to the growth, regeneration, lifelong maintenance, and sarcopenia-related deterioration of the neuromuscular system. We employ murine models, injury and transplant paradigms, cell isolation techniques, cell culture systems, gene expression analysis, high-resolution imaging methods, and assessment of neuromuscular function to determine how specific stem and progenitor cell populations, molecules of interest, and inflammatory-related signals regulate neuromuscular development, regeneration, and aging.
Our studies have thus far established; interrelationships between age-related stem cell and neuromuscular decline, the involvement of stem cells in neuromuscular regeneration, cell-specific roles for inflammation during neuromuscular regeneration, the cellular basis for juvenile neuromuscular growth, and contributors to lifelong neuromuscular decline in response to stressors such as DNA damaging paediatric cancer therapies. We hope insights gained from our studies can be exploited to identify therapeutic strategies that promote neuromuscular regenerative capacity and lifelong maintenance in a variety of contexts.
Academic Articles
- Leinroth, Abigail P., Anthony J. Mirando, Douglas Rouse, Yoshihiko Kobayahsi, Purushothama Rao Tata, Helen E. Rueckert, Yihan Liao, Jason T. Long, Joe V. Chakkalakal, and Matthew J. Hilton. “Identification of distinct non-myogenic skeletal-muscle-resident mesenchymal cell populations.” Cell Rep 39, no. 6 (May 10, 2022): 110785. https://doi.org/10.1016/j.celrep.2022.110785.
- Bachman, John F., and Joe V. Chakkalakal. “Insights into muscle stem cell dynamics during postnatal development.” Febs J 289, no. 10 (May 2022): 2710–22. https://doi.org/10.1111/febs.15856.
- O’Connor, Thomas N., Jacob G. Kallenbach, Haley M. Orciuoli, Nicole D. Paris, John F. Bachman, Carl J. Johnston, Eric Hernady, Jacqueline P. Williams, Robert T. Dirksen, and Joe V. Chakkalakal. “Endurance exercise attenuates juvenile irradiation-induced skeletal muscle functional decline and mitochondrial stress.” Skelet Muscle 12, no. 1 (April 12, 2022): 8. https://doi.org/10.1186/s13395-022-00291-y.
- Kallenbach, Jacob G., John F. Bachman, Nicole D. Paris, Roméo S. Blanc, Thomas O’Connor, Esraa Furati, Jacqueline P. Williams, and Joe V. Chakkalakal. “Muscle-specific functional deficits and lifelong fibrosis in response to paediatric radiotherapy and tumour elimination.” J Cachexia Sarcopenia Muscle 13, no. 1 (February 2022): 296–310. https://doi.org/10.1002/jcsm.12902.
- Larouche, Jacqueline A., Mahir Mohiuddin, Jeongmoon J. Choi, Peter J. Ulintz, Paula Fraczek, Kaitlyn Sabin, Sethuramasundaram Pitchiaya, et al. “Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging.” Elife 10 (July 29, 2021). https://doi.org/10.7554/eLife.66749.
- Cole, Calvin L., John F. Bachman, Jian Ye, Joseph Murphy, Scott A. Gerber, Christopher A. Beck, Brendan F. Boyce, et al. “Increased myocellular lipid and IGFBP-3 expression in a pre-clinical model of pancreatic cancer-related skeletal muscle wasting.” J Cachexia Sarcopenia Muscle 12, no. 3 (June 2021): 731–45. https://doi.org/10.1002/jcsm.12699.
- Bachman, John F., Roméo S. Blanc, Nicole D. Paris, Jacob G. Kallenbach, Carl J. Johnston, Eric Hernady, Jacqueline P. Williams, and Joe V. Chakkalakal. “Radiation-Induced Damage to Prepubertal Pax7+ Skeletal Muscle Stem Cells Drives Lifelong Deficits in Myofiber Size and Nuclear Number.” Iscience 23, no. 11 (November 20, 2020): 101760. https://doi.org/10.1016/j.isci.2020.101760.
- Paris, Nicole D., Jacob G. Kallenbach, John F. Bachman, Roméo S. Blanc, Carl J. Johnston, Eric Hernady, Jacqueline P. Williams, and Joe V. Chakkalakal. “Chemoradiation impairs myofiber hypertrophic growth in a pediatric tumor model.” Sci Rep 10, no. 1 (November 11, 2020): 19501. https://doi.org/10.1038/s41598-020-75913-w.
- Blanc, Roméo S., Jacob G. Kallenbach, John F. Bachman, Amanda Mitchell, Nicole D. Paris, and Joe V. Chakkalakal. “Inhibition of inflammatory CCR2 signaling promotes aged muscle regeneration and strength recovery after injury.” Nat Commun 11, no. 1 (August 20, 2020): 4167. https://doi.org/10.1038/s41467-020-17620-8.
- Li, Jinbo, Xiangjiao Yi, Zhenqiang Yao, Joe V. Chakkalakal, Lianping Xing, and Brendan F. Boyce. “TNF Receptor-Associated Factor 6 Mediates TNFα-Induced Skeletal Muscle Atrophy in Mice During Aging.” J Bone Miner Res 35, no. 8 (August 2020): 1535–48. https://doi.org/10.1002/jbmr.4021.
- Pan, Chunliu, Neha Jaiswal Agrawal, Yanni Zulia, Shalini Singh, Kai Sha, James L. Mohler, Kevin H. Eng, Joe V. Chakkalakal, John J. Krolewski, and Kent L. Nastiuk. “Prostate tumor-derived GDF11 accelerates androgen deprivation therapy-induced sarcopenia.” Jci Insight 5, no. 6 (March 26, 2020). https://doi.org/10.1172/jci.insight.127018.
- Bell, Richard D., Emily K. Wu, Christopher A. Rudmann, Megan Forney, Claire R. W. Kaiser, Ronald W. Wood, Joe V. Chakkalakal, et al. “Selective Sexual Dimorphisms in Musculoskeletal and Cardiopulmonary Pathologic Manifestations and Mortality Incidence in the Tumor Necrosis Factor-Transgenic Mouse Model of Rheumatoid Arthritis.” Arthritis Rheumatol 71, no. 9 (September 2019): 1512–23. https://doi.org/10.1002/art.40903.
- Yue, Li, MA Hassan Talukder, Anagha Gurjar, Jung Il Lee, Mark Noble, Robert T. Dirksen, Joe Chakkalakal, and John C. Elfar. “4-Aminopyridine attenuates muscle atrophy after sciatic nerve crush injury in mice.” Muscle Nerve 60, no. 2 (August 2019): 192–201. https://doi.org/10.1002/mus.26516.
- Bachman, John F., Alanna Klose, Wenxuan Liu, Nicole D. Paris, Roméo S. Blanc, Melissa Schmalz, Emma Knapp, and Joe V. Chakkalakal. “Prepubertal skeletal muscle growth requires Pax7-expressing satellite cell-derived myonuclear contribution.” Development 145, no. 20 (October 25, 2018). https://doi.org/10.1242/dev.167197.
- Klose, Alanna, Wenxuan Liu, Nicole D. Paris, Sophie Forman, John J. Krolewski, Kent L. Nastiuk, and Joe V. Chakkalakal. “Castration induces satellite cell activation that contributes to skeletal muscle maintenance.” Jcsm Rapid Communications 1, no. 1 (January 2018): 1–16. https://doi.org/10.1002/j.2617-1619.2018.tb00004.x.
- Dunne, Richard F., Karen M. Mustian, Jose M. Garcia, William Dale, Reid Hayward, Breton Roussel, Mary M. Buschmann, et al. “Research priorities in cancer cachexia: The University of Rochester Cancer Center NCI Community Oncology Research Program Research Base Symposium on Cancer Cachexia and Sarcopenia.” Curr Opin Support Palliat Care 11, no. 4 (December 2017): 278–86. https://doi.org/10.1097/SPC.0000000000000301.
- Liu, Wenxuan, Alanna Klose, Sophie Forman, Nicole D. Paris, Lan Wei-LaPierre, Mariela Cortés-Lopéz, Aidi Tan, et al. “Loss of adult skeletal muscle stem cells drives age-related neuromuscular junction degeneration.” Elife 6 (June 6, 2017). https://doi.org/10.7554/eLife.26464.
- Paris, Nicole D., Andrew Soroka, Alanna Klose, Wenxuan Liu, and Joe V. Chakkalakal. “Smad4 restricts differentiation to promote expansion of satellite cell derived progenitors during skeletal muscle regeneration.” Elife 5 (November 18, 2016). https://doi.org/10.7554/eLife.19484.
- Pan, Chunliu, Shalini Singh, Deepak M. Sahasrabudhe, Joe V. Chakkalakal, John J. Krolewski, and Kent L. Nastiuk. “TGFβ Superfamily Members Mediate Androgen Deprivation Therapy-Induced Obese Frailty in Male Mice.” Endocrinology 157, no. 11 (November 2016): 4461–72. https://doi.org/10.1210/en.2016-1580.
- Williams, Jacqueline P., Laura Calvi, Joe V. Chakkalakal, Jacob N. Finkelstein, M Kerry O’Banion, and Edward Puzas. “Addressing the Symptoms or Fixing the Problem? Developing Countermeasures against Normal Tissue Radiation Injury.” Radiat Res 186, no. 1 (July 2016): 1–16. https://doi.org/10.1667/RR14473.1.
- Liu, Wenxuan, Lan Wei-LaPierre, Alanna Klose, Robert T. Dirksen, and Joe V. Chakkalakal. “Inducible depletion of adult skeletal muscle stem cells impairs the regeneration of neuromuscular junctions.” Elife 4 (August 27, 2015). https://doi.org/10.7554/eLife.09221.
- Chakkalakal, Joe V., Josef Christensen, Wanyi Xiang, Mathew T. Tierney, Francesca S. Boscolo, Alessandra Sacco, and Andrew S. Brack. “Early forming label-retaining muscle stem cells require p27kip1 for maintenance of the primitive state.” Development 141, no. 8 (April 2014): 1649–59. https://doi.org/10.1242/dev.100842.
- Chakkalakal, Joe V., Kieran M. Jones, M Albert Basson, and Andrew S. Brack. “The aged niche disrupts muscle stem cell quiescence.” Nature 490, no. 7420 (October 18, 2012): 355–60. https://doi.org/10.1038/nature11438.
- Chakkalakal, Jv, and As Brack. “Extrinsic Regulation of Satellite Cell Function and Muscle Regeneration Capacity during Aging.” J Stem Cell Res Ther Suppl 11 (September 26, 2012): 001. https://doi.org/10.4172/2157-7633.S11-001.
- Chakkalakal, Joe V., Shihuan Kuang, Mario Buffelli, Jeff W. Lichtman, and Joshua R. Sanes. “Mouse transgenic lines that selectively label Type I, Type IIA, and Types IIX+B skeletal muscle fibers.” Genesis 50, no. 1 (January 2012): 50–58. https://doi.org/10.1002/dvg.20794.
- Chakkalakal, Joe V., Hiroshi Nishimune, Jorge L. Ruas, Bruce M. Spiegelman, and Joshua R. Sanes. “Retrograde influence of muscle fibers on their innervation revealed by a novel marker for slow motoneurons.” Development 137, no. 20 (October 2010): 3489–99. https://doi.org/10.1242/dev.053348.
- Miura, Pedro, Joe V. Chakkalakal, Louise Boudreault, Guy Bélanger, Richard L. Hébert, Jean-Marc Renaud, and Bernard J. Jasmin. “Pharmacological activation of PPARbeta/delta stimulates utrophin A expression in skeletal muscle fibers and restores sarcolemmal integrity in mature mdx mice.” Hum Mol Genet 18, no. 23 (December 1, 2009): 4640–49. https://doi.org/10.1093/hmg/ddp431.
- Chakkalakal, Joe V., Pedro Miura, Guy Bélanger, Robin N. Michel, and Bernard J. Jasmin. “Modulation of utrophin A mRNA stability in fast versus slow muscles via an AU-rich element and calcineurin signaling.” Nucleic Acids Res 36, no. 3 (February 2008): 826–38. https://doi.org/10.1093/nar/gkm1107.
- Michel, R. N., E. R. Chin, J. V. Chakkalakal, J. K. Eibl, and B. J. Jasmin. “Erratum: Ca2+/calmodulin-based signalling in the regulation of the muscle fibre phenotype and its therapeutic potential via modulation of utrophin A and myostatin expression (Applied Physiology, Nutrition and Metabolism (2007) 32, (921-929)).” Applied Physiology, Nutrition and Metabolism 32, no. 6 (December 1, 2007): 1274. https://doi.org/10.1139/H07-157.
- Michel, Robin N., Eva R. Chin, Joe V. Chakkalakal, Joe K. Eibl, and Bernard J. Jasmin. “Ca2+/calmodulin-based signalling in the regulation of the muscle fibre phenotype and its therapeutic potential via modulation of utrophin A and myostatin expression.” Appl Physiol Nutr Metab 32, no. 5 (October 2007): 921–29. https://doi.org/10.1139/H07-093.
- Chakkalakal, Joe V., Stephanie A. Michel, Eva R. Chin, Robin N. Michel, and Bernard J. Jasmin. “Targeted inhibition of Ca2+ /calmodulin signaling exacerbates the dystrophic phenotype in mdx mouse muscle.” Hum Mol Genet 15, no. 9 (May 1, 2006): 1423–35. https://doi.org/10.1093/hmg/ddl065.
- Angus, Lindsay M., Joe V. Chakkalakal, Alexandre Méjat, Joe K. Eibl, Guy Bélanger, Lynn A. Megeney, Eva R. Chin, Laurent Schaeffer, Robin N. Michel, and Bernard J. Jasmin. “Calcineurin-NFAT signaling, together with GABP and peroxisome PGC-1{alpha}, drives utrophin gene expression at the neuromuscular junction.” Am J Physiol Cell Physiol 289, no. 4 (October 2005): C908–17. https://doi.org/10.1152/ajpcell.00196.2005.
- Davies, K. E. “Regulation of utrophin in transgenic mice.” Neuromuscul Disord 15, no. 9–10 (October 2005): 648. https://doi.org/10.1016/j.nmd.2005.06.013.
- Stocksley, Mark A., Joe V. Chakkalakal, Amanda Bradford, Pedro Miura, Yves De Repentigny, Rashmi Kothary, and Bernard J. Jasmin. “Reply to Davies.” Neuromuscular Disorders 15, no. 9–10 (October 2005): 648–49. https://doi.org/10.1016/j.nmd.2005.06.014.
- Miura, Pedro, Jennifer Thompson, Joe V. Chakkalakal, Martin Holcik, and Bernard J. Jasmin. “The utrophin A 5'-untranslated region confers internal ribosome entry site-mediated translational control during regeneration of skeletal muscle fibers.” J Biol Chem 280, no. 38 (September 23, 2005): 32997–5. https://doi.org/10.1074/jbc.M503994200.
- Chakkalakal, Joe V., Jennifer Thompson, Robin J. Parks, and Bernard J. Jasmin. “Molecular, cellular, and pharmacological therapies for Duchenne/Becker muscular dystrophies.” Faseb J 19, no. 8 (June 2005): 880–91. https://doi.org/10.1096/fj.04-1956rev.
- Stocksley, Mark A., Joe V. Chakkalakal, Amanda Bradford, Pedro Miura, Yves De Repentigny, Rashmi Kothary, and Bernard J. Jasmin. “A 1.3 kb promoter fragment confers spatial and temporal expression of utrophin A mRNA in mouse skeletal muscle fibers.” Neuromuscul Disord 15, no. 6 (June 2005): 437–49. https://doi.org/10.1016/j.nmd.2005.03.008.
- St-Pierre, Simon J. G., Joe V. Chakkalakal, Steven M. Kolodziejczyk, Jennifer C. Knudson, Bernard J. Jasmin, and Lynn A. Megeney. “Glucocorticoid treatment alleviates dystrophic myofiber pathology by activation of the calcineurin/NF-AT pathway.” Faseb J 18, no. 15 (December 2004): 1937–39. https://doi.org/10.1096/fj.04-1859fje.
- Chakkalakal, Joe V., Mary-Ann Harrison, Salvatore Carbonetto, Eva Chin, Robin N. Michel, and Bernard J. Jasmin. “Stimulation of calcineurin signaling attenuates the dystrophic pathology in mdx mice.” Hum Mol Genet 13, no. 4 (February 15, 2004): 379–88. https://doi.org/10.1093/hmg/ddh037.
- Chakkalakal, Joe V., Mark A. Stocksley, Mary-Ann Harrison, Lindsay M. Angus, Julie Deschenes-Furry, Simon St-Pierre, Lynn A. Megeney, Eva R. Chin, Robin N. Michel, and Bernard J. Jasmin. “Expression of utrophin A mRNA correlates with the oxidative capacity of skeletal muscle fiber types and is regulated by calcineurin/NFAT signaling.” Proc Natl Acad Sci U S A 100, no. 13 (June 24, 2003): 7791–96. https://doi.org/10.1073/pnas.0932671100.
- Chakkalakal, Joe V., and Bernard J. Jasmin. “Localizing synaptic mRNAs at the neuromuscular junction: it takes more than transcription.” Bioessays 25, no. 1 (January 2003): 25–31. https://doi.org/10.1002/bies.10205.
- Jasmin, Bernard J., Lindsay M. Angus, Guy Bélanger, Joe V. Chakkalakal, Anthony O. Gramolini, John A. Lunde, Mark A. Stocksley, and Jennifer Thompson. “Multiple regulatory events controlling the expression and localization of utrophin in skeletal muscle fibers: insights into a therapeutic strategy for Duchenne muscular dystrophy.” J Physiol Paris 96, no. 1–2 (January 2002): 31–42. https://doi.org/10.1016/s0928-4257(01)00078-x.
- Gramolini, A. O., G. Bélanger, J. M. Thompson, J. V. Chakkalakal, and B. J. Jasmin. “Increased expression of utrophin in a slow vs. a fast muscle involves posttranscriptional events.” Am J Physiol Cell Physiol 281, no. 4 (October 2001): C1300–1309. https://doi.org/10.1152/ajpcell.2001.281.4.C1300.
Book Sections
Liu, Wenxuan, and Joe V. Chakkalakal. “The Composition, Development, and Regeneration of Neuromuscular Junctions.,” 126:99–124, 2018. https://doi.org/10.1016/bs.ctdb.2017.08.005.
Contact
Joe Chakkalakal
Associate Professor
Duke University School of Medicine
Departments of Orthopaedic Surgery and Cell Biology
Orthopaedic, Developmental and Genome Laboratories
DUMC 91009
308 Research Drive, LSRC B321B
Durham, NC 27710
919-668-5664
joe.chakkalakal@duke.edu
https://sites.duke.edu/chakkalakallab/
He/Him/His/Himself