Pulmonary & Critical Care Fellowship Program
MGH BIDMC Harvard Medical School

David Lagares

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David Lagares, PhD

Instructor in Medicine

 

 

 

 

Academic Interests

Dr. Lagares’s research interests focus on tissue repair, regeneration and fibrosis. His research laboratory concentrates on understanding the fundamental mechanisms that balance tissue regeneration and fibrosis following injury. Ultimately, his laboratory seeks to develop novel anti-fibrotic therapies aimed at reducing tissue fibrosis and promoting the regeneration of damaged organs for the treatment of human fibrotic diseases such as idiopathic pulmonary fibrosis, systemic sclerosis, liver cirrhosis, progressive kidney disease and desmoplastic tumors. Dr. Lagares has made multiple seminal contributions to this field including the identification of the ADAM10-sEphrin-B2 pathway in lung injury and fibrosis and the use of BH3 mimetic drugs to induce myofibroblast apoptosis and reversion of established fibrosis. Dr. Lagares’s laboratory is affiliated with the Division of Pulmonary and Critical Care Medicine at the Massachusetts General Hospital (MGH). He is also a Principal Investigator at Center for Immunology and Inflammatory Diseases (CIID) and serves as the Director of the Matrix and Mechanobiology Program at the MGH Fibrosis Research Center.

Awards and Recognition

Dr. Lagares’s has received numerous awards and honors, including The Marie Coyle Research Grant awarded by the Scleroderma Foundation (2015), the ATS Foundation/Pulmonary Fibrosis Foundation Research Grant (2016) and the Scleroderma Research Foundation Grant (2017). His research work has been recognized and awarded at the national and international level in multiple scientific meetings including the American Thoracic Society International Conference, the International Colloquium On Lung And Airway Fibrosis, the Keystone Symposia Conference or the Japan College of Rheumatology International Conference. Dr. Lagares serves as Ad hoc Reviewer for the study section of The Medical Research Council (United Kingdom), The Health Research Board (Ireland), The National Plan for Spanish Research and Development Board (Spain) and The Agency for Medical Research and Development (Japan), and as a reviewer for many high profile peer-review scientific journals, including Nature Medicine, The Journal of Clinical Investigation, American Journal of Respiratory Cell and Molecular Biology and Arthritis & Rheumatism.

 

A full list of Dr. Lagares’s published work can be found on My Bibliography.

More information can be found on Dr. Lagares's Harvard Catalyst profile.

 

 

 

+Current Projects

  • The ADAM10-sEphrin-B2 pathway in lung injury and fibrosis
  • Targeted apoptosis of myofibroblasts in fibrosis
  • Mechanobiology of fibrotic diseases
  • Biomarkers for Idiopathic Pulmonary Fibrosis

+Selected Publications

Research articles

  • Lagares D, Ghassemi-Kakaroodi P, Tremblay C, Wu J, Ahluwalia N, Probst CK, Grasberger P, B. Montesi S, Shea BS, Black KE, Knipe R, Blati M, Baron M, Fahmi H, Gandhi R, Pardo A, Selman M, Pelletier JP, Martel-Pelletier J, Tager AM and Kapoor M*. ADAM10-mediated ephrin-B2 shedding drives myofibroblast activation and tissue fibrosis. Nature Medicine. December 2017. PMID: 29058717 PMCID: PMC5720906
  • Lagares D*, Fei L, Grasberger P, Probst CK, Sakai N, Ryan J, Bhola P, Montero J, Kapoor M, Baron M, Tschumperlin DJ, Letai A and Tager AM. Targeted apoptosis of myofibroblasts with the BH3 mimetic ABT-253 reverses established fibrosis. Science Translational Medicine. December 2017. PMID: 29237758
  • 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. December 2017. PMID: 29211497
  • 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. March 2017. PMID: 27927603 PMCID: PMC5313343
  • 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. June 2016. PMID: 26600305
  • Liu F, Lagares D, Choi KM, Stopfer L, Marinković 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 drive fibroblast activation and fibrosis. Am J Physiol Lung Cell Mol Physiol. February 2015. PMID: 25502501
  • Lagares D, Busnadiego O, García-Fernández RA, Kapoor M, Liu S, Carter D, Abraham D, Shi-Wen X, Carreira P, Fontaine B, Shea BS, Tager AM, Leask A, Lamas S and Rodríguez-Pascual F*. Inhibition of focal adhesion kinase prevents experimental lung fibrosis and myofibroblast formation. Arthritis Rheum. May 2012. PMID: 22492165
  • Lagares D, García-Fernández RA, López-Jiménez C, Magán-Marchal N, Busnadiego O, Lamas S and Rodríguez-Pascual F. Endothelin-1 Contributes to the Effect of Transforming Growth Factor 1 on Wound Repair and Skin Fibrosis. Arthritis Rheum. March 2010. PMID: 201312411.

Reviews

  • Lagares D and Kapoor M. Targeting focal adhesion kinase in fibrotic diseases. BioDrugs. February 2013. PMID: 23329396
  • Ho Y, Lagares D, Tager AM and Kapoor M. Fibrosis— a lethal component of systemic sclerosis. Nature Reviews Rheumatology. July 2014. PMID: 24752182
  • Santos A, Lagares D*. Matrix Stiffness: The Conductor of Fibrosis. Current Rheumatology Reviews Jan 2018. PMID: 293497034.
  • Kuehl T, Lagares D*. BH3 mimetics as anti-fibrotic therapy: Unleashing the mitochondrial pathway of apoptosis in myofibroblasts. Matrix Biology. Feb 2018. PMID: 29408011