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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.

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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. Lagares D. P-311 in Scar Wars: Myofibroblasts Lost without TGFß Translation. Am J Respir Cell Mol Biol. 2018 Oct 02. PMID: 30277809.
    View in: PubMed
  2. 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 Apr; 58(4):471-481. PMID: 29211497.
    View in: PubMed
  3. Kuehl T, Lagares D. BH3 mimetics as anti-fibrotic therapy: Unleashing the mitochondrial pathway of apoptosis in myofibroblasts. Matrix Biol. 2018 Aug; 68-69:94-105. PMID: 29408011.
    View in: PubMed
  4. Santos A, Lagares D. Matrix Stiffness: the Conductor of Organ Fibrosis. Curr Rheumatol Rep. 2018 Jan 19; 20(1):2. PMID: 29349703.
    View in: PubMed
  5. 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.
    View in: PubMed
  6. 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.
    View in: PubMed
  7. 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.
    View in: PubMed
  8. 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.
    View in: PubMed
  9. 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.
    View in: PubMed
  10. 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 [Available on 06/01/17].
  11. 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.
  12. 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.
  13. 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; PMCID: PMC4279729.
  14. 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.
    View in: PubMed
  15. 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.
    View in: PubMed
  16. 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; PMCID: PMC3700097.
  17. Lagares D, Kapoor M. Targeting focal adhesion kinase in fibrotic diseases. BioDrugs. 2013 Feb; 27(1):15-23. PMID: 23329396.
    View in: PubMed
  18. 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.
    View in: PubMed
  19. 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.
  20. 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.
    View in: PubMed
  21. 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.
    View in: PubMed
  22. 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.
  23. 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.
    View in: PubMed
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Funded by the NIH/NCATS Clinical and Translational Science Award (CTSA) program, grant number UL1TR001102, and through institutional support from Harvard University, Harvard Medical School, Harvard T.H. Chan School of Public Health, Beth Israel Deaconess Medical Center, Boston Children's Hospital, Brigham and Women's Hospital, Massachusetts General Hospital and the Dana Farber Cancer Institute.