ABOUT THE RESEARCHER

OVERVIEW

The unifying theme in my research is to understand the molecular mechanisms of early cellular mechanotransduction, the process whereby cells sense and convert mechanical force into biochemical signaling. This is particularly important in understanding and designing treatment strategies for a syndrome known as Ventilator Induced Lung Injury (VILI) whereby a respirator (ventilator) used to keep patients with respiratory failure, and in particular Acute Respiratory Distress Syndrome (ARDS) alive induces inflammation and contributes to mortality via multi-organ failure and death.

My initial bench research at CHB was in the Ingber Laboratory in the Vascular Biology Program and focused on the analysis of the viscoelastic properties of individual focal adhesions (molecular structures used by cells to attach to extracellular matrix through which mechanical force is applied to cells), cellular adaptation responses to mechanical stress, and the biochemical signaling pathways responsible for these cell behaviors. These studies were made possible through the design of permanent and electromagnetic devices that were used to pull on cells through bound ligand coated magnetic beads. Our recent studies led to the discovery that force applied to vascular endothelial cells induces near instantaneous (<10 ms) activation of TRPV4 (a stretch activated membrane ion channel) leading to transient localized calcium influx. This calcium response is one of the most rapid force induced biochemical signaling events detected to date, and represents an important pharmaceutical target in the treatment of VILI as calcium initiates many mechanical signaling pathways which regulate inflammation in ARDS and VILI.

My current interest is in using an ex-vivo mouse lung ventilation perfusion model to study the mechanisms of VILI and to develop drug delivery systems (in collaboration with Dr. Dan Kohane (MIT and Dept Anesthesia/CHB) to pre-treat VILI and other diseases of the lung.

 

 

BACKGROUND

Dr. Matthews received an MD from McGill University in Montreal, Canada. He completed a residency in Pediatrics at Schneider Children’s Hospital in New York, and a fellowship in Pediatric Critical Care Medicine at the Hospital for Sick Children in Toronto, Canada. Following his fellowship in Toronto, he worked as a staff physician at the Massachusetts General Hospital in Boston in the Pediatric Intensive Care Unit, where he also served as the Fellowship Program Director in Pediatric Critical Care Medicine. He is currently a staff physician in the Medicine Intensive Care Unit at Children’s Hospital Boston.

PUBLICATIONS

Publications powered by Harvard Catalyst Profiles

  1. Molecular mapping of transmembrane mechanotransduction through the ß1 integrin-CD98hc-TRPV4 axis. J Cell Sci. 2020 Nov 02; 133(20). View abstract
  2. PR1P Stabilizes VEGF and Upregulates Its Signaling to Reduce Elastase-induced Murine Emphysema. Am J Respir Cell Mol Biol. 2020 10; 63(4):452-463. View abstract
  3. AAV-mediated gene therapy targeting TRPV4 mechanotransduction for inhibition of pulmonary vascular leakage. APL Bioeng. 2019 Dec; 3(4):046103. View abstract
  4. Pregnancy and parental leave among obstetrics and gynecology residents: results of a nationwide survey of program directors. Am J Obstet Gynecol. 2018 08; 219(2):199.e1-199.e8. View abstract
  5. A novel strategy to enhance angiogenesis in vivo using the small VEGF-binding peptide PR1P. Angiogenesis. 2017 Aug; 20(3):399-408. View abstract
  6. Prevention of ventilator-induced lung edema by inhalation of nanoparticles releasing ruthenium red. Am J Respir Cell Mol Biol. 2014 Jun; 50(6):1107-17. View abstract
  7. Strain-induced differentiation of fetal type II epithelial cells is mediated via the integrin a6ß1-ADAM17/tumor necrosis factor-a-converting enzyme (TACE) signaling pathway. J Biol Chem. 2013 Aug 30; 288(35):25646-57. View abstract
  8. A human disease model of drug toxicity-induced pulmonary edema in a lung-on-a-chip microdevice. Sci Transl Med. 2012 Nov 07; 4(159):159ra147. View abstract
  9. Shear-activated nanotherapeutics for drug targeting to obstructed blood vessels. Science. 2012 Aug 10; 337(6095):738-42. View abstract
  10. Rapamycin suppresses self-renewal and vasculogenic potential of stem cells isolated from infantile hemangioma. J Invest Dermatol. 2011 Dec; 131(12):2467-76. View abstract
  11. Ultra-rapid activation of TRPV4 ion channels by mechanical forces applied to cell surface beta1 integrins. Integr Biol (Camb). 2010 Sep; 2(9):435-42. View abstract
  12. Reconstituting organ-level lung functions on a chip. Science. 2010 Jun 25; 328(5986):1662-8. View abstract
  13. Inhaled prophylactic nanotherapy for lung protection from Ventilator induced Lung Injury and Acute Respiratory Distress Syndrome (ARDS). 2010. View abstract
  14. High-throughput Screen Identifies Rapamycin as a Drug to Suppress Self-Renewal and Vasculogenesis in Infantile Hemangioma. Journal of Cell Investigation (In Review). 2010. View abstract
  15. Ultra-rapid activation of TRPV4 ion channels by mechanical forces applied to cell surface β1 integrins. . Integrative Biology (In Review). 2010. View abstract
  16. TRPV4 channels mediate cyclic strain-induced endothelial cell reorientation through integrin-to-integrin signaling. Circ Res. 2009 May 08; 104(9):1123-30. View abstract
  17. Wheeze detection in the pediatric intensive care unit: comparison among physician, nurses, respiratory therapists, and a computerized respiratory sound monitor. Respir Care. 2008 Oct; 53(10):1304-9. View abstract
  18. Rheological behavior of living cells is timescale-dependent. Biophys J. 2007 Oct 15; 93(8):L39-41. View abstract
  19. Tools to study cell mechanics and mechanotransduction. Methods Cell Biol. 2007; 83:443-72. View abstract
  20. Tools to study cell mechanotransduction. In: Wang Y, Discher D., editors. Methods in Cell Biology. 2007; 441-472. View abstract
  21. Integrin-dependent force transmission to mechanosensitive ion channels. In: Hammill O, editors. Mechanosensitive Ion Channels. 2007; 59-85. View abstract
  22. Alpha-actinin-4 is required for normal podocyte adhesion. J Biol Chem. 2007 Jan 05; 282(1):467-77. View abstract
  23. Cellular adaptation to mechanical stress: role of integrins, Rho, cytoskeletal tension and mechanosensitive ion channels. J Cell Sci. 2006 Feb 01; 119(Pt 3):508-18. View abstract
  24. Alpha4beta1-dependent adhesion strengthening under mechanical strain is regulated by paxillin association with the alpha4-cytoplasmic domain. J Cell Biol. 2005 Dec 19; 171(6):1073-84. View abstract
  25. Novel dynamic rheological behavior of individual focal adhesions measured within single cells using electromagnetic pulling cytometry. Acta Biomater. 2005 May; 1(3):295-303. View abstract
  26. Mechanical properties of individual focal adhesions probed with a magnetic microneedle. Biochem Biophys Res Commun. 2004 Jan 16; 313(3):758-64. View abstract
  27. SGMD: the Soybean Genomics and Microarray Database. Nucleic Acids Res. 2004 Jan 01; 32(Database issue):D398-400. View abstract
  28. Electromagnetic needles with submicron pole tip radii for nanomanipulation of biomolecules and living cells. Applied Physics Letters. 2004; 85:2968-2970.. View abstract
  29. Management of oxygenation in pediatric acute hypoxemic respiratory failure. Pediatr Pulmonol. 2001 Dec; 32(6):459-70. View abstract
  30. Role of the actin cytoskeleton in insulin action. Microsc Res Tech. 1999 Oct 15; 47(2):79-92. View abstract
  31. Nucleotide sequence of 10 kilobases of rat tyrosine aminotransferase gene 5' flanking region. Nucleic Acids Res. 1989 Nov 11; 17(21):8877-8. View abstract