Research

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Benjamin Matthews, MD

Benjamin Matthews
Program:
Computational Health Informatics Program (CHIP)Vascular Biology Program
Hospital Title:
Staff Physician
Academic Title:
Assistant Professor in Pediatrics Harvard Medical School

Research 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.

About Benjamin Matthews

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

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  1. Jurek SC, Hirano-Kobayashi M, Chiang H, Kohane DS, Matthews BD. 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.
  2. Huh D, Leslie DC, Matthews BD, Fraser JP, Jurek S, Hamilton GA, Thorneloe KS, McAlexander MA, Ingber DE. A human disease model of drug toxicity-induced pulmonary edema in a lung-on-a-chip microdevice. Sci Transl Med. 2012 Nov 7; 4(159):159ra147.
  3. Korin N, Kanapathipillai M, Matthews BD, Crescente M, Brill A, Mammoto T, Ghosh K, Jurek S, Bencherif SA, Bhatta D, Coskun AU, Feldman CL, Wagner DD, Ingber DE. Shear-activated nanotherapeutics for drug targeting to obstructed blood vessels. Science. 2012 Aug 10; 337(6095):738-42.
  4. Matthews BD, Thodeti CK, Tytell JD, Mammoto A, Overby DR, Ingber DE. 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.
  5. Matthews, B, Kohane, D, Ingber, D. Inhaled prophylactic nanotherapy for lung protection from Ventilator induced Lung Injury and Acute Respiratory Distress Syndrome (ARDS). 2010.
  6. Greenberger, S, Yuan, S, Walsh, L., Boscolo, E., Kang, K.T., Matthews, B, Mulliken, J.B., and Bischoff, J. . High-throughput Screen Identifies Rapamycin as a Drug to Suppress Self-Renewal and Vasculogenesis in Infantile Hemangioma. Journal of Cell Investigation (In Review). 2010.
  7. Matthews, B.D, Thodeti, C.K., Tytell, JD., Mammoto, A., Overby, D.R., and Ingber, D.E. . Ultra-rapid activation of TRPV4 ion channels by mechanical forces applied to cell surface &#946;1 integrins. . Integrative Biology (In Review). 2010.
  8. Prodhan P, Dela Rosa RS, Shubina M, Haver KE, Matthews BD, Buck S, Kacmarek RM, Noviski NN. 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.
  9. Stamenovic D, Rosenblatt N, Montoya-Zavala M, Matthews BD, Hu S, Suki B, Wang N, Ingber DE. Rheological behavior of living cells is timescale-dependent. Biophys J. 2007 Oct 15; 93(8):L39-41.
  10. Lele TP, Sero JE, Matthews BD, Kumar S, Xia S, Montoya-Zavala M, Polte T, Overby D, Wang N, Ingber DE. Tools to study cell mechanics and mechanotransduction. Methods Cell Biol. 2007; 83:443-72.
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  12. Lele T, Sero J, Matthews BD, Kumar S, Xia S, Montoya-Zavala M, Polte T, Overby DR, Wang N and Ingber DE. . Tools to study cell mechanotransduction. In: Wang Y, Discher D., editors. Methods in Cell Biology. 2007; 441-472.
  13. Matthews BD, Thodeti CK and Ingber DE. . Integrin-dependent force transmission to mechanosensitive ion channels. In: Hammill O, editors. Mechanosensitive Ion Channels. 2007; 59-85.
  14. Matthews BD, Overby DR, Mannix R, Ingber DE. Cellular adaptation to mechanical stress: role of integrins, Rho, cytoskeletal tension and mechanosensitive ion channels. J Cell Sci. 2006 Feb 1; 119(Pt 3):508-18.
  15. Alon R, Feigelson SW, Manevich E, Rose DM, Schmitz J, Overby DR, Winter E, Grabovsky V, Shinder V, Matthews BD, Sokolovsky-Eisenberg M, Ingber DE, Benoit M, Ginsberg MH. 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.
  16. Overby DR, Matthews BD, Alsberg E, Ingber DE. Novel dynamic rheological behavior of individual focal adhesions measured within single cells using electromagnetic pulling cytometry. Acta Biomater. 2005 May; 1(3):295-303.
  17. Alkharouf NW, Matthews BF. SGMD: the Soybean Genomics and Microarray Database. Nucleic Acids Res. 2004 Jan 1; 32(Database issue):D398-400.
  18. Matthews, B. D., LaVan, D. A., Overby, D. R., Karavitis, J. and Ingber, D. E. . Electromagnetic needles with submicron pole tip radii for nanomanipulation of biomolecules and living cells. Applied Physics Letters. 2004; 85:2968-2970..
  19. Tsakiridis T, Tong P, Matthews B, Tsiani E, Bilan PJ, Klip A, Downey GP. Role of the actin cytoskeleton in insulin action. Microsc Res Tech. 1999 Oct 15; 47(2):79-92.
  20. Oddos J, Grange T, Carr KD, Matthews B, Roux J, Richard-Foy H, Pictet R. Nucleotide sequence of 10 kilobases of rat tyrosine aminotransferase gene 5' flanking region. Nucleic Acids Res. 1989 Nov 11; 17(21):8877-8.
  21. Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE. Reconstituting organ-level lung functions on a chip. Science. 2010 Jun 25; 328(5986):1662-8.
  22. Thodeti CK, Matthews B, Ravi A, Mammoto A, Ghosh K, Bracha AL, Ingber DE. TRPV4 channels mediate cyclic strain-induced endothelial cell reorientation through integrin-to-integrin signaling. Circ Res. 2009 May 8; 104(9):1123-30.
  23. Matthews BD, Overby DR, Alenghat FJ, Karavitis J, Numaguchi Y, Allen PG, Ingber DE. Mechanical properties of individual focal adhesions probed with a magnetic microneedle. Biochem Biophys Res Commun. 2004 Jan 16; 313(3):758-64.
  24. Greenberger S, Yuan S, Walsh LA, Boscolo E, Kang KT, Matthews B, Mulliken JB, Bischoff J. Rapamycin suppresses self-renewal and vasculogenic potential of stem cells isolated from infantile hemangioma. J Invest Dermatol. 2011 Dec; 131(12):2467-76.
  25. Matthews BD, Noviski N. Management of oxygenation in pediatric acute hypoxemic respiratory failure. Pediatr Pulmonol. 2001 Dec; 32(6):459-70.
  26. Dandapani SV, Sugimoto H, Matthews BD, Kolb RJ, Sinha S, Gerszten RE, Zhou J, Ingber DE, Kalluri R, Pollak MR. Alpha-actinin-4 is required for normal podocyte adhesion. J Biol Chem. 2007 Jan 5; 282(1):467-77.
  27. Wang Y, Huang Z, Nayak PS, Matthews BD, Warburton D, Shi W, Sanchez-Esteban J. 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.
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