While publications are not the only metric for a lab's success (fun at Karoke counts as well, and so do awards!), we pride ourselves on quality papers that are published in many of the leading orthopedic and translational research journals.  The research is a collaborative effort between junior and senior lab members, as well as collaborators within UCSF as well as nationally.  Below is a summary of some of our key papers, which is updated relatively regularly.  

Wang Z, Liu X, Liu M, Jiang K, Kajimura S, Kim H, Feeley BT. β3-Adrenergic receptor agonist treats rotator cuff fatty infiltration by activating beige fat in mice. J Shoulder Elbow Surg. 2021 Feb;30(2):373-386. doi: 10.1016/j.jse.2020.06.006. Epub 2020 Jun 27. PMID: 32599287; PMCID: PMC7765745.  In this study, we found that treatment of FAPs with a 'beiging' agent results in less fatty infiltration by driving FAPs into a pro-myogenic state. 

Agha O, Mueller-Immergluck A, Liu M, Zhang H, Theologis AA, Clark A, Kim HT, Liu X, Feeley BT, Bailey JF. Intervertebral disc herniation effects on multifidus muscle composition and resident stem cell populations. JOR Spine. 2020 May 6;3(2):e1091. doi: 10.1002/jsp2.1091. PMID: 32613166; PMCID: PMC7323461.  This study shows that patients with lumbar disk injury have an increase in the number of FAPs present in the muscle, which may be why there is an increase in fatty infiltration. 

Agha O, Diaz A, Davies M, Kim HT, Liu X, Feeley BT. Rotator cuff tear degeneration and the role of fibro-adipogenic progenitors. Ann N Y Acad Sci. 2021 Apr;1490(1):13-28. doi: 10.1111/nyas.14437. Epub 2020 Jul 29. PMID: 32725671; PMCID: PMC7855559.

This study is a review by our medical student, AJ Agha, where they discuss the role of FAPs in rotator cuff tears. 


Liu X, Liu M, Lee L, Davies M, Wang Z, Kim H, Feeley BT. Trichostatin A Regulates Fibro/adipogenic Progenitor Adipogenesis Epigenetically and Reduces

Rotator Cuff Muscle Fatty Infiltration. J Orthop Res. 2020 Sep 24. doi:10.1002/jor.24865.  PMID: 32970360.

This study demonstrated that treatment of injured rotator cuff muscle with a histone deacetylase inhibitor, Trichostatin A, decreases fibroadipogenic progenitor-mediated fatty infiltration and muscle atrophy. 

Feeley BT, Liu M, Ma CB, Agha O, Aung M, Lee C, Liu X. Human Rotator Cuff Tears Have an Endogenous, Inducible Stem Cell Source Capable of Improving Muscle

Quality and Function After Rotator Cuff Repair. Am J Sports Med. 2020 Sep;48(11):2660-2668. doi: 10.1177/0363546520935855. Epub 2020 Jul 30. PMID:


This study is the first study that shows the FAP cell population in human rotator cuff tears.  We found that patients with rotator cuff tears had more FAPs if they were older, and if the tears were larger.  The FAP stem cells were inducible to a pro-myogenic beige fat phenotype.  This study proved that these stem cells are the likely cellular source of fatty infiltration and likely promote muscle atrophy.


Agha O, Diaz A, Davies M, Kim HT, Liu X, Feeley BT. Rotator cuff tear degeneration and the role of fibro-adipogenic progenitors. Ann N Y Acad Sci.

2020 Jul 29. doi: 10.1111/nyas.14437. Epub ahead of print. PMID: 32725671.


Agha O, Mueller-Immergluck A, Liu M, Zhang H, Theologis AA, Clark A, Kim HT, Liu X, Feeley BT, Bailey JF. Intervertebral disc herniation effects on

multifidus muscle composition and resident stem cell populations. JOR Spine. 2020 May 6;3(2):e1091. doi: 10.1002/jsp2.1091. PMID: 32613166; PMCID:


In a collaborative effort with the UCSF spine surgery team, we found that low back pain patients have increased FAP cells, which likely contributes to the muscle degeneration seen in the large paraspinal muscles.


Lee C, Liu M, Agha O, Kim HT, Liu X, Feeley BT. Beige fibro-adipogenic progenitor transplantation reduces muscle degeneration and improves function in a mouse model of delayed repair of rotator cuff tears. J Shoulder Elbow Surg. 2019 Nov 26. pii: S1058-2746(19)30648-2. doi: 10.1016/j.jse.2019.09.021. 
PMID: 31784382
We performed FAP stem cell transplantation to improve outcomes after rotator cuff injury in a mouse model of rotator cuff repair. Cell transplantation diminished fibrosis, FI, and atrophy and enhanced vascularization in both delayed repair models. Cell transplantation resulted in improved shoulder function as assessed with gait analysis in both the delayed repair models.

Wang Z, Liu X, Davies MR, Horne D, Kim H, Feeley BT.
A Mouse Model of Delayed Rotator Cuff Repair Results in Persistent Muscle Atrophy and Fatty Infiltration. Am J Sports Med. 2018 Oct;46(12):2981-2989. doi: 10.1177/0363546518793403. Epub 2018 Sep 10.
This study evaluated a novel mouse model that we developed to study rotator cuff repairs. We found that a mouse model was able to reproduce a phenomenon we have seen in clinical populations: that even in the setting of a successful repair, there is persistent atrophy and fatty infiltration. We also used gait analysis (picture a teeny tiny treadmill) to show that shoulder function was not as good as if there had been no injury or repair. We are currently using this model to evaluate treatment strategies to improve rotator cuff function by stimulating stem cell development.  

Wang Z, Feeley BT, Kim HT, Liu X.
Reversal of Fatty Infiltration After Suprascapular Nerve Compression Release Is Dependent on UCP1 Expression in Mice.
Clin Orthop Relat Res. 2018 Aug;476(8):1665-1679. doi: 10.1097/CORR.0000000000000335.
This study looked at the influence of nerve injury in the development of fatty infiltration and muscle atrophy.  We were able to develop a reversible nerve injury and show that re-innervation results in improved muscle quality through increased FAP/beige fat expression.

Liu X, Ravishankar B, Ning A, Liu M, Kim HT, Feeley BT. Knocking-out matrix metalloproteinase-13 exacerbates rotator cuff muscle fatty infiltration. Muscles
Ligaments Tendons J.
2017 Sep 18;7(2):202-207. doi: 10.11138/mltj/2017.7.2.202. eCollection 2017 Apr-Jun. PubMed PMID: 29264329; PubMed Central PMCID:
Matrix metalloproteinase-13 plays a crucial role in extracellular matrix remodeling in many physiological and pathological processes. Nevertheless, its role in rotator cuff muscle atrophy and fatty infiltration remains unknown. Six weeks after RC surgery, no significant difference in muscle atrophy and fibrosis between MMP-13 knockout and wild type mice was observed. However, there was a significant increase in the amount of fatty infiltration in MMP-13 knockout mice compared to the wild types. Results from this study suggest that MMP-13 plays a crucial role in rotator cuff muscle fatty degeneration. This novel finding suggests a new molecular mechanism that governs RC muscle FI and MMP-13 may serve as a target for therapeutics to treat muscle FI after RC tears.
Davies MR, Garcia S, Tamaki S, Liu X, Lee S, Jose A, Pomerantz JH, Feeley BT. Muscle Stem Cell Activation in a Mouse Model of Rotator Cuff Injury. J Orthop
2017 Aug 8. doi: 10.1002/jor.23679. [Epub ahead of print] PubMed PMID: 28786534; PubMed Central PMCID: PMC5803476.
In this study, we characterized the longitudinal effect of rotator cuff (RC) tendon injury on the muscle stem cell (MuSC) population in mice, using a mouse model of rotator cuff tear. We found that MuSCs are transiently activated following injury before returning to their baseline state, and are not depleted, in spite of persistent muscle atrophy. Thus, factors beyond the MuSC population may be primarily responsible for the atrophy seen after RC tears, however, retained MuSCs in injured RC muscle represent a source of cells which may be induced to participate in repair to improve clinical outcomes.
Davies MR, Lee L, Feeley BT, Kim HT, Liu X. Lysophosphatidic acid-induced RhoA signaling and prolonged macrophage infiltration worsens fibrosis and fatty
infiltration following rotator cuff tears. J Orthop Res. 2017 Jul;35(7):1539-1547. doi: 10.1002/jor.23384. Epub 2016 Aug 19. PubMed PMID:
27505847; PubMed Central PMCID: PMC5502767.
We used the RhoA activator lysophosphatidic acid (LPA) to potentiate an inflammatory state within injured rotator cuff muscle in a mouse model of rotator cuff (RC) tear. We found that increasing RhoA signaling using LPA increased the number of CD68+ macrophages in injured muscle, which correlated with worsened rotator cuff atrophy, fibrosis, and fatty infiltration. Together, our results suggest that macrophage-mediated inflammation may play an important role in the pathogenesis of muscle degeneration following RC tear, and may represent a target for new treatments to improve muscle quality following this injury.

Liu X, Ning AY, Chang NC, Kim H, Nissenson R, Wang L, Feeley BT. Investigating the cellular origin of rotator cuff muscle fatty infiltration and fibrosis after  injury. Muscles Ligaments Tendons J. 2016 May 19;6(1):6-15. doi: 10.11138/mltj/2016.6.1.006. PubMed PMID: 27331027; PubMed Central PMCID: PMC4915463.  While this went into a smaller journal, this study was key in showing that FAPs are the cellular source of fatty infiltration. 

Liu X, Joshi SK, Ravishankar B, Laron D, Kim HT, Feeley BT. Upregulation of transforming growth factor-β signaling in a rat model of rotator cuff tears. J Shoulder Elbow Surg. 2014 Nov;23(11):1709-16. doi: 10.1016/j.jse.2014.02.029. PubMed PMID: 24875732; PubMed Central PMCID: PMC4198422.

Liu X, Laron D, Natsuhara K, Manzano G, Kim HT, Feeley BT. A mouse model of massive rotator cuff tears. J Bone Joint Surg Am. 2012 Apr 4;94(7):e41. doi:10.2106/JBJS.K.00620. PubMed PMID: 22488625.  This is our model paper that has developed into the primary model used in the study of mouse rotator cuff injuries. 

Liu X, Joshi SK, Samagh SP, Dang YX, Laron D, Lovett DH, Bodine SC, Kim HT, Feeley BT. Evaluation of Akt/mTOR activity in muscle atrophy after rotator cuff tears in a rat model. J Orthop Res. 2012 Sep;30(9):1440-6. doi: 10.1002/jor.22096. PubMed PMID: 22378614.  Our first molecular pathway study!

Laron D, Samagh SP, Liu X, Kim HT, Feeley BT. Muscle degeneration in rotator cuff tears. J Shoulder Elbow Surg. 2012 Feb;21(2):164-74. doi: 10.1016/j.jse.2011.09.027. Review. PubMed PMID: 22244059.  Our first review article!

Liu X, Manzano G, Kim HT, Feeley BT. A rat model of massive rotator cuff tears. J Orthop Res. 2011 Apr;29(4):588-95. doi: 10.1002/jor.21266. PubMed PMID:  20949443.  Over a decade ago, this was our first research paper together. 

Clinical Studies

Several studies have been done evaluating the clinical outcomes in rotator cuff injury and repair.  We are also looking at how high resolution MRI can be used to detect changes in muscle quality with Drew Lansdown, MD and the imaging experts at UCSF.  Please see PubMed for a more updated list of rotator cuff and shoulder arthroplasty based papers. 


What are we reading? 

Here are some important relevant papers that we have found to be critical in understanding the role of FAPs from other members of the scientific community, as well as some great technique papers:

Uezumi A, Ikemoto-Uezumi M, Zhou H, Kurosawa T, Yoshimoto Y, Nakatani M, Hitachi K, Yamaguchi H, Wakatsuki S, Araki T, Morita M, Yamada H, Toyoda M, Kanazawa N, Nakazawa T, Hino J, Fukada SI, Tsuchida K. Mesenchymal Bmp3b expression maintains skeletal muscle integrity and decreases in age-related sarcopenia. J Clin Invest. 2021 Jan 4;131(1):e139617. doi: 10.1172/JCI139617. PMID: 33170806; PMCID: PMC7773381.

Wosczyna MN, Perez Carbajal EE, Wagner MW, Paredes S, Konishi CT, Liu L, Wang TT, Walsh RA, Gan Q, Morrissey CS, Rando TA. Targeting microRNA-mediated gene repression limits adipogenic conversion of skeletal muscle mesenchymal stromal cells. Cell Stem Cell. 2021 Jul 1;28(7):1323-1334.e8. doi: 10.1016/j.stem.2021.04.008. Epub 2021 May 3. PMID: 33945794; PMCID: PMC8254802.

Wosczyna MN, Konishi CT, Perez Carbajal EE, Wang TT, Walsh RA, Gan Q, Wagner MW, Rando TA. Mesenchymal Stromal Cells Are Required for Regeneration and Homeostatic Maintenance of Skeletal Muscle. Cell Rep. 2019 May 14;27(7):2029-2035.e5. doi: 10.1016/j.celrep.2019.04.074. PMID: 31091443; PMCID: PMC7034941.

Dunn TW, Marshall JD, Severson KS, Aldarondo DE, Hildebrand DGC, Chettih SN, Wang WL, Gellis AJ, Carlson DE, Aronov D, Freiwald WA, Wang F, Ölveczky BP. Geometric deep learning enables 3D kinematic profiling across species and environments. Nat Methods. 2021 May;18(5):564-573. doi: 10.1038/s41592-021-01106-6. Epub 2021 Apr 19. PMID: 33875887.