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David Lagares, Ph.D.

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David Lagares, PhD

Assistant Professor of Medicine
Harvard Medical School

Director Matrix and Mechanobiology Program
Massachusetts General Hospital

Lagares Laboratory: Tissue Repair, Regeneration and Fibrosis


The ability of organs to regenerate following injury declines with age. In older aged individuals, chronic tissue injury leads to abnormal wound healing responses characterized by the development of scar tissue or fibrosis and subsequent organ failure. The identification of novel therapeutic strategies aiming at reducing tissue fibrosis and promoting the regeneration of damaged tissues is a major unmet clinical need in regenerative medicine.

The goal of the Lagares Laboratory is to understand the cellular and molecular mechanisms that regulate the delicate balance between organ regeneration and fibrosis following tissue injury, with an emphasis on the biochemical and biomechanical drivers of scar-forming myofibroblast activation. Ultimately, we seek to develop novel anti-fibrotic therapies for the treatment of human diseases such as idiopathic pulmonary fibrosis, systemic sclerosis, liver cirrhosis, progressive kidney disease and desmoplastic tumors.

The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. R01HL147059 (LAGARES, DAVID) Apr 1, 2019 - Mar 31, 2024
    Targeting the ADAM10-sEphrin-B2 pathway in pulmonary fibrosis
    Role: Principal Investigator

Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Jeong MH, Han H, Lagares D, Im H. Recent Advances in Molecular Diagnosis of Pulmonary Fibrosis for Precision Medicine. ACS Pharmacol Transl Sci. 2022 Aug 12; 5(8):520-538. PMID: 35983278; PMCID: PMC9379941.
    Citations: 1     
  2. Dieffenbach PB, Mallarino Haeger C, Rehman R, Corcoran AM, Coronata AMF, Vellarikkal SK, Chrobak I, Waxman AB, Vitali SH, Sholl LM, Padera RF, Lagares D, Polverino F, Owen CA, Fredenburgh LE. A Novel Protective Role for Matrix Metalloproteinase-8 in the Pulmonary Vasculature. Am J Respir Crit Care Med. 2021 12 15; 204(12):1433-1451. PMID: 34550870; PMCID: PMC8865706.
    Citations: 3     Fields:    Translation:HumansAnimalsCells
  3. Merkt W, Zhou Y, Han H, Lagares D. Myofibroblast fate plasticity in tissue repair and fibrosis: Deactivation, apoptosis, senescence and reprogramming. Wound Repair Regen. 2021 07; 29(4):678-691. PMID: 34117675.
    Citations: 2     Fields:    Translation:HumansCells
  4. O'Hare M, Amarnani D, Whitmore HAB, An M, Marino C, Ramos L, Delgado-Tirado S, Hu X, Chmielewska N, Chandrahas A, Fitzek A, Heinrich F, Steurer S, Ondruschka B, Glatzel M, Krasemann S, Sepulveda-Falla D, Lagares D, Pedron J, Bushweller JH, Liu P, Arboleda-Velasquez JF, Kim LA. Targeting Runt-Related Transcription Factor 1 Prevents Pulmonary Fibrosis and Reduces Expression of Severe Acute Respiratory Syndrome Coronavirus 2 Host Mediators. Am J Pathol. 2021 07; 191(7):1193-1208. PMID: 33894177; PMCID: PMC8059259.
    Citations: 5     Fields:    Translation:AnimalsCells
  5. Han H, Lagares D. RNA Sequencing Uncovers Antifibrotic Genes during Lung Fibrosis Resolution. Am J Respir Cell Mol Biol. 2021 04; 64(4):401-402. PMID: 33556298.
    Citations:    Fields:    Translation:Humans
  6. Mueller AC, Piper M, Goodspeed A, Bhuvane S, Williams JS, Bhatia S, Phan AV, Van Court B, Zolman KL, Peña B, Oweida AJ, Zakem S, Meguid C, Knitz MW, Darragh L, Bickett TE, Gadwa J, Mestroni L, Taylor MRG, Jordan KR, Dempsey P, Lucia MS, McCarter MD, Del Chiaro M, Messersmith WA, Schulick RD, Goodman KA, Gough MJ, Greene CS, Costello JC, Neto AG, Lagares D, Hansen KC, Van Bokhoven A, Karam SD. Induction of ADAM10 by Radiation Therapy Drives Fibrosis, Resistance, and Epithelial-to-Mesenchyal Transition in Pancreatic Cancer. Cancer Res. 2021 06 15; 81(12):3255-3269. PMID: 33526513; PMCID: PMC8260469.
    Citations: 6     Fields:    Translation:HumansAnimalsCellsPHPublic Health
  7. Zhou Y, Lagares D. Methods for Studying Myofibroblast Apoptotic Pathways. Methods Mol Biol. 2021; 2299:123-137. PMID: 34028739.
    Citations:    Fields:    Translation:HumansCells
  8. Lagares D, Hinz B. Animal and Human Models of Tissue Repair and Fibrosis: An Introduction. Methods Mol Biol. 2021; 2299:277-290. PMID: 34028750.
    Citations: 2     Fields:    Translation:HumansAnimalsCells
  9. Kadry H, Lagares D, Al-Hilal TA. Method for Investigating Fibroblast Durotaxis. Methods Mol Biol. 2021; 2299:227-236. PMID: 34028747.
    Citations:    Fields:    Translation:HumansAnimalsCells
  10. Sato T, Verma S, Andrade CDC, Omeara M, Campbell N, Wang JS, Cetinbas M, Lang A, Ausk BJ, Brooks DJ, Sadreyev RI, Kronenberg HM, Lagares D, Uda Y, Pajevic PD, Bouxsein ML, Gross TS, Wein MN. A FAK/HDAC5 signaling axis controls osteocyte mechanotransduction. Nat Commun. 2020 07 01; 11(1):3282. PMID: 32612176; PMCID: PMC7329900.
    Citations: 22     Fields:    Translation:HumansAnimalsCells
  11. Tschumperlin DJ, Lagares D. Mechano-therapeutics: Targeting Mechanical Signaling in Fibrosis and Tumor Stroma. Pharmacol Ther. 2020 08; 212:107575. PMID: 32437826.
    Citations: 19     Fields:    Translation:HumansAnimalsCells
  12. Adams DC, Szabari MV, Lagares D, McCrossan AF, Hariri LP, Tager AM, Suter MJ. Assessing the progression of systemic sclerosis by monitoring the tissue optic axis using PS-OCT. Sci Rep. 2020 02 13; 10(1):2561. PMID: 32054932.
    Citations: 5     Fields:    Translation:HumansAnimals
  13. Merkt W, Bueno M, Mora AL, Lagares D. Senotherapeutics: Targeting senescence in idiopathic pulmonary fibrosis. Semin Cell Dev Biol. 2020 05; 101:104-110. PMID: 31879264.
    Citations: 17     Fields:    Translation:HumansAnimals
  14. Hinz B, Lagares D. Evasion of apoptosis by myofibroblasts: a hallmark of fibrotic diseases. Nat Rev Rheumatol. 2020 01; 16(1):11-31. PMID: 31792399; PMCID: PMC7913072.
    Citations: 89     Fields:    Translation:HumansAnimalsCells
  15. Haak AJ, Kostallari E, Sicard D, Ligresti G, Choi KM, Caporarello N, Jones DL, Tan Q, Meridew J, Diaz Espinosa AM, Aravamudhan A, Maiers JL, Britt RD, Roden AC, Pabelick CM, Prakash YS, Nouraie SM, Li X, Zhang Y, Kass DJ, Lagares D, Tager AM, Varelas X, Shah VH, Tschumperlin DJ. Selective YAP/TAZ inhibition in fibroblasts via dopamine receptor D1 agonism reverses fibrosis. Sci Transl Med. 2019 10 30; 11(516). PMID: 31666402; PMCID: PMC7066514.
    Citations: 41     Fields:    Translation:HumansAnimalsCells
  16. Wu B, Rockel JS, Lagares D, Kapoor M. Ephrins and Eph Receptor Signaling in Tissue Repair and Fibrosis. Curr Rheumatol Rep. 2019 04 12; 21(6):23. PMID: 30980212; PMCID: PMC7112176.
    Citations: 8     Fields:    Translation:HumansAnimalsCells
  17. Lagares D. P311 in Scar Wars: Myofibroblasts Lost without Transforming Growth Factor ß Translation. Am J Respir Cell Mol Biol. 2019 02; 60(2):139-140. PMID: 30277809.
    Citations: 2     Fields:    Translation:HumansCells
  18. Knipe RS, Probst CK, Lagares D, Franklin A, Spinney JJ, Brazee PL, Grasberger P, Zhang L, Black KE, Sakai N, Shea BS, Liao JK, Medoff BD, Tager AM. The Rho Kinase Isoforms ROCK1 and ROCK2 Each Contribute to the Development of Experimental Pulmonary Fibrosis. Am J Respir Cell Mol Biol. 2018 04; 58(4):471-481. PMID: 29211497; PMCID: PMC5894496.
    Citations: 29     Fields:    Translation:HumansAnimalsCells
  19. Kuehl T, Lagares D. BH3 mimetics as anti-fibrotic therapy: Unleashing the mitochondrial pathway of apoptosis in myofibroblasts. Matrix Biol. 2018 08; 68-69:94-105. PMID: 29408011.
    Citations: 12     Fields:    Translation:HumansAnimalsCells
  20. Santos A, Lagares D. Matrix Stiffness: the Conductor of Organ Fibrosis. Curr Rheumatol Rep. 2018 01 19; 20(1):2. PMID: 29349703.
    Citations: 39     Fields:    Translation:HumansCells
  21. Lagares D, Santos A, Grasberger PE, Liu F, Probst CK, Rahimi RA, Sakai N, Kuehl T, Ryan J, Bhola P, Montero J, Kapoor M, Baron M, Varelas X, Tschumperlin DJ, Letai A, Tager AM. Targeted apoptosis of myofibroblasts with the BH3 mimetic ABT-263 reverses established fibrosis. Sci Transl Med. 2017 Dec 13; 9(420). PMID: 29237758.
    Citations: 59     Fields:    Translation:HumansAnimalsCells
  22. Lagares D, Ghassemi-Kakroodi P, Tremblay C, Santos A, Probst CK, Franklin A, Santos DM, Grasberger P, Ahluwalia N, Montesi SB, Shea BS, Black KE, Knipe R, Blati M, Baron M, Wu B, Fahmi H, Gandhi R, Pardo A, Selman M, Wu J, Pelletier JP, Martel-Pelletier J, Tager AM, Kapoor M. ADAM10-mediated ephrin-B2 shedding promotes myofibroblast activation and organ fibrosis. Nat Med. 2017 Dec; 23(12):1405-1415. PMID: 29058717; PMCID: PMC5720906.
    Citations: 41     Fields:    Translation:AnimalsCells
  23. Sakai N, Chun J, Duffield JS, Lagares D, Wada T, Luster AD, Tager AM. Lysophosphatidic acid signaling through its receptor initiates profibrotic epithelial cell fibroblast communication mediated by epithelial cell derived connective tissue growth factor. Kidney Int. 2017 03; 91(3):628-641. PMID: 27927603; PMCID: PMC5313343.
    Citations: 19     Fields:    Translation:AnimalsCells
  24. Funke M, Knudsen L, Lagares D, Ebener S, Probst CK, Fontaine BA, Franklin A, Kellner M, Kühnel M, Matthieu S, Grothausmann R, Chun J, Roberts JD, Ochs M, Tager AM. Lysophosphatidic Acid Signaling through the Lysophosphatidic Acid-1 Receptor Is Required for Alveolarization. Am J Respir Cell Mol Biol. 2016 07; 55(1):105-16. PMID: 27082727; PMCID: PMC4942205.
    Citations: 9     Fields:    Translation:AnimalsCells
  25. Ahluwalia N, Grasberger PE, Mugo BM, Feghali-Bostwick C, Pardo A, Selman M, Lagares D, Tager AM. Fibrogenic Lung Injury Induces Non-Cell-Autonomous Fibroblast Invasion. Am J Respir Cell Mol Biol. 2016 06; 54(6):831-42. PMID: 26600305; PMCID: PMC4942213.
    Citations: 11     Fields:    Translation:HumansAnimalsCells
  26. Black KE, Berdyshev E, Bain G, Castelino FV, Shea BS, Probst CK, Fontaine BA, Bronova I, Goulet L, Lagares D, Ahluwalia N, Knipe RS, Natarajan V, Tager AM. Autotaxin activity increases locally following lung injury, but is not required for pulmonary lysophosphatidic acid production or fibrosis. FASEB J. 2016 06; 30(6):2435-50. PMID: 27006447; PMCID: PMC4871797.
    Citations: 15     Fields:    Translation:Animals
  27. Vasheghani F, Zhang Y, Li YH, Blati M, Fahmi H, Lussier B, Roughley P, Lagares D, Endisha H, Saffar B, Lajeunesse D, Marshall WK, Rampersaud YR, Mahomed NN, Gandhi R, Pelletier JP, Martel-Pelletier J, Kapoor M. PPAR? deficiency results in severe, accelerated osteoarthritis associated with aberrant mTOR signalling in the articular cartilage. Ann Rheum Dis. 2015 Mar; 74(3):569-78. PMID: 25573665; PMCID: PMC4345902.
    Citations: 74     Fields:    Translation:AnimalsCells
  28. Liu F, Lagares D, Choi KM, Stopfer L, Marinkovic A, Vrbanac V, Probst CK, Hiemer SE, Sisson TH, Horowitz JC, Rosas IO, Fredenburgh LE, Feghali-Bostwick C, Varelas X, Tager AM, Tschumperlin DJ. Mechanosignaling through YAP and TAZ drives fibroblast activation and fibrosis. Am J Physiol Lung Cell Mol Physiol. 2015 Feb 15; 308(4):L344-57. PMID: 25502501; PMCID: PMC4329470.
    Citations: 291     Fields:    Translation:HumansAnimalsCellsCTClinical Trials
  29. Busnadiego O, Loureiro-Álvarez J, Sandoval P, Lagares D, Dotor J, Pérez-Lozano ML, López-Armada MJ, Lamas S, López-Cabrera M, Rodríguez-Pascual F. A pathogenetic role for endothelin-1 in peritoneal dialysis-associated fibrosis. J Am Soc Nephrol. 2015 Jan; 26(1):173-82. PMID: 25012164.
    Citations: 12     Fields:    Translation:HumansAnimalsCells
  30. Ho YY, Lagares D, Tager AM, Kapoor M. Fibrosis--a lethal component of systemic sclerosis. Nat Rev Rheumatol. 2014 Jul; 10(7):390-402. PMID: 24752182.
    Citations: 114     Fields:    Translation:HumansCells
  31. Zhang Y, Vasheghani F, Li YH, Blati M, Simeone K, Fahmi H, Lussier B, Roughley P, Lagares D, Pelletier JP, Martel-Pelletier J, Kapoor M. Cartilage-specific deletion of mTOR upregulates autophagy and protects mice from osteoarthritis. Ann Rheum Dis. 2015 Jul; 74(7):1432-40. PMID: 24651621.
    Citations: 149     Fields:    Translation:HumansAnimalsCells
  32. Busnadiego O, González-Santamaría J, Lagares D, Guinea-Viniegra J, Pichol-Thievend C, Muller L, Rodríguez-Pascual F. LOXL4 is induced by transforming growth factor ß1 through Smad and JunB/Fra2 and contributes to vascular matrix remodeling. Mol Cell Biol. 2013 Jun; 33(12):2388-401. PMID: 23572561.
    Citations: 40     Fields:    Translation:HumansAnimalsCells
  33. Lagares D, Kapoor M. Targeting focal adhesion kinase in fibrotic diseases. BioDrugs. 2013 Feb; 27(1):15-23. PMID: 23329396.
    Citations: 22     Fields:    Translation:HumansAnimalsCells
  34. Lagares D, Busnadiego O, García-Fernández RA, Lamas S, Rodríguez-Pascual F. Adenoviral gene transfer of endothelin-1 in the lung induces pulmonary fibrosis through the activation of focal adhesion kinase. Am J Respir Cell Mol Biol. 2012 Dec; 47(6):834-42. PMID: 22962065.
    Citations: 18     Fields:    Translation:HumansAnimalsCells
  35. Lagares D, Busnadiego O, García-Fernández RA, Kapoor M, Liu S, Carter DE, Abraham D, Shi-Wen X, Carreira P, Fontaine BA, Shea BS, Tager AM, Leask A, Lamas S, Rodríguez-Pascual F. Inhibition of focal adhesion kinase prevents experimental lung fibrosis and myofibroblast formation. Arthritis Rheum. 2012 May; 64(5):1653-64. PMID: 22492165; PMCID: PMC3338902.
    Citations: 70     Fields:    Translation:HumansAnimalsCells
  36. Rodríguez-Pascual F, Busnadiego O, Lagares D, Lamas S. Role of endothelin in the cardiovascular system. Pharmacol Res. 2011 Jun; 63(6):463-72. PMID: 21296157.
    Citations: 28     Fields:    Translation:Humans
  37. Lagares D, García-Fernández RA, Jiménez CL, Magán-Marchal N, Busnadiego O, Lamas S, Rodríguez-Pascual F. Endothelin 1 contributes to the effect of transforming growth factor beta1 on wound repair and skin fibrosis. Arthritis Rheum. 2010 Mar; 62(3):878-89. PMID: 20131241.
    Citations: 30     Fields:    Translation:AnimalsCells
  38. Rodríguez-Pascual F, Redondo-Horcajo M, Magán-Marchal N, Lagares D, Martínez-Ruiz A, Kleinert H, Lamas S. Glyceraldehyde-3-phosphate dehydrogenase regulates endothelin-1 expression by a novel, redox-sensitive mechanism involving mRNA stability. Mol Cell Biol. 2008 Dec; 28(23):7139-55. PMID: 18809573; PMCID: PMC2593384.
    Citations: 48     Fields:    Translation:HumansCells
  39. Ramírez de Molina A, Gallego-Ortega D, Sarmentero-Estrada J, Lagares D, Gómez Del Pulgar T, Bandrés E, García-Foncillas J, Lacal JC. Choline kinase as a link connecting phospholipid metabolism and cell cycle regulation: implications in cancer therapy. Int J Biochem Cell Biol. 2008; 40(9):1753-63. PMID: 18296102.
    Citations: 38     Fields:    Translation:HumansAnimalsCells
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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.