Principal Research Scientist
My main research interest is fluid mechanics and particle behavior in the lungs. Currently I have two major areas of investigation.
#1: Our lab studies particle-lung interactions. We track particles from airspace to bloodstream. This research includes studying 1) transport and deposition processes of aerosol particles in the respiratory tract, 2) interaction of nano-size particles with the liquid layer lining the alveolar surface, 3) translocation of nano-size particles across the alveolar epithelium into the septal interstitium, subsequent rapid migration to the regional lymph nodes, and eventually to bloodstream.
Particle deposition: we discovered that submicron particles in the alveoli follow kinematically irreversible trajectories, which are driven by chaotic dynamics associated with alveolar recirculation. With this new finding, the enhancement of particle deposition observed experimentally in the gas exchange region can be explained.
Submersion of nanoparticles in the alveolar liquid layer: we are developing a mechanistic model to quantify the effects of the pulmonary surfactant on the motion of particles (i.e., Marangoni force laterally; contact angle force toward the epithelial cell surface).
Translocation of nanoparticles across the alveolar epithelium: we are examining the behavior of particles and how their physicochemical characteristics (e.g., size and surface charge) determine their behavior. Our current findings can be applied to design and optimize particles for drug delivery by inhalation therapy as well as for the assessment of the health effects of various particulate pollutants by distinguishing specific subclasses which can cross the alveolar epithelium rapidly, and may disseminate in the body.
Particles in the developing lung: lung development continues after birth, which includes not only growth in lung size, but also the generation of an alveolated structure with complex vasculature. It is therefore highly likely that particle-lung interactions in the postnatally developing lungs of young children are different from those in the adult lungs. Our studies also include analyses of age-dependent changes in gene expression profiles of postnatally developing lungs exposed to various particles in an animal model.
We also study the translocation of nanoparticles from nasal cavities to the brain. This route may offer a direct path to the brain for therapeutic particles to treat neurological disorders.
#2: Another project focuses on compensatory lung growth after the surgical removal of one lung (i.e., pneumonectomy). The hypothesis we are working on is that parenchymal deformation may trigger lung regeneration. Using microCT scanning, we are developing 3-dimensional finite element geometric models of the murine lung pre- and post-pneumonectomy. Comparing the pre- vs. the post-operation lung shapes, we compute deformation of lung parenchyma caused by the pneumonectomy and spatially correlate to histology. The initial results appear to show that the highly stretched regions –mainly subpleural regions of the cardiac lobe– coincide with previously identified growth patterns.
- BSME (1979), Kyoto University of Industrial Arts, Japan
- MS (1982), Ph.D. (1986), Worcester Polytechnique Institute
Sites of Note
- Chaotic mixing (http://www.nature.com/news/2002/020716/full/news020715-2.html)
- Rapid trans-epithelium translocation of nanoparticles
- Nanoparicle delivery in infant lungs (https://www.hsph.harvard.edu/news/features/features/lung-health-particle-deposits-tsuda.html) (http://www.rsc.org/chemistryworld/News/2012/March/nanoparticle-toxicity-children-lungs.asp)
- Molecular and Integrative Physiological Sciences (https://www.hsph.harvard.edu/research/mips)
- Harvard NIEHS Center for Environmental Health (https://www.hsph.harvard.edu/research/niehs)
Fredberg JJ, Tsuda A. Continuum scaling for spreading drops. Nature, vol.340, pp24, 1989. (sci. corres.)
Tsuda A, Henry FS, Butler JP. Chaotic mixing of alveolated duct flow in rhythmically expanding pulmonary acinus. J. Appl. Physiol., 79(3):1055-1063, 1995.
Butler JP, Tsuda A. Effect of convective stretching and folding on aerosol mixing deep in the lung, assessed by approximate entropy. J. Appl. Physiol., 83(3):800-809, 1997.
Tsuda A, Stringer BK, Mijailovich SM, Rogers RA, Hamada K, Gray ML. Alveolar cell stretching in the presence of fibrous particles induced IL-8 responses. Am. J. Respir. Cell Mol. Biol., 21:455-462, 1999.
Haber S, Butler JP, Brenner H, Emanuel I, Tsuda A. Shear flow over a self-similar expanding pulmonary alveolus rhythmical breathing. J. Fluid Mech. 405:243-268, 2000.
Tsuda A, Rogers RA, Hydon PE, Butler JP. Chaotic mixing deep in the lung. Proc. Natl. Acad. Sci. USA 99:10173-10178, 2002.
Ravnic DJ, Konerding MA, Tsuda A, Huss HT, Wolloscheck T, Pratt JP, Mentzer SJ. Structural adaptations in the murine colon microcirculation associated with hapten-induced inflammation. Gut. 56(4):518-523, 2007.
Dickie R, Wang YT, Butler JP, Schulz H, Tsuda A. Distribution and Quantity of Contractile Tissue in Postnatal Development of Rat Alveolar Interstitium. Anatom. Rec. A. 291:83-93, 2007.
Bolle I, Eder G, Takenaka S, Ganguly K, Zeller C, Neuner M, Kreyling WG, Tsuda A, Schulz H. Postnatal Lung function in the developing rat lung. J. Appl. Physiol. 104: 1167–1176, 2008
Tsuda A, Filipovic N, Haberthür D, Dickie R, Stampanoni M, Matsui Y, Schittny JC. Finite Element 3D Reconstruction of the pulmonary acinus imaged by Synchrotron X-ray tomography. J. Appl. Physiol. 105:964–976, 2008.
Dickie R, Cormack M, Kreyling WG, Semmler-Behnke M, Tsuda A. Deep pulmonary lymphatics in immature lungs J. Appl. Physiol. 107(3): 859 – 863, 2009.
Karrasch S. Eder G., Bolle I., Tsuda A., Schulz H. Breath-by-breath measurement of intrapulmonary particle deposition in spontaneously breathing rats. J. Appl. Physiol. 107(4): 1293 – 1299, 2009.
Henry FS, Laine-Pearson FE, Tsuda A. Hamiltonian chaos in a model alveolus. ASME J. Biomech. Eng. 131(1):011006-1-7, 2009.
Matsui Y, Sakai N, Tsuda A, Tarada Y, Takaoka M, Fujimaki H, Uchiyama I. Tracking the pathway of diesel exhaust particles from the nose to the brain by X-ray florescence analysis. Spectrochimica Acta Part B. 64:796-801, 2009.
Berntsen P, Park CY, Rothen-Rutishauser B, Tsuda A, Sager TM, Molina RM, Donaghey TC, Alencar AM, Kasahara DI, Ericsson T, Millet EJ, Tschumperlin DJ,Butler JP, Brain JD, Fredberg JJ, Gehr P, Zhou EH. Biomechanical effects of environmental and engineered particulates on human airway smooth muscle cells. J. Royal Soc. Interface 7 Suppl 3:S331-340, 2010.
Mijailovich S, Kojic M, Tsuda A. Particle-induced indentation of the alveolar epithelium caused by surface tension forces. J. Appl. Physiol. 109(4):1179-1194, 2010.
Lee GS, Filipovic N, Miele LF, Lin M, Collings-Simpson D, Gibney B, Konerding MA, Tsuda A, Mentzer SJ. Blood flow shapes intravascular pillar geometry in the chick chorioallantoic membrane. J. Angiogenesis Research 2:11, 2010.
Choi HS, Ashitate Y, Lee JH, Kim SH, Matsui A, Insin N, Bawendi MG, Semmler-Behnke M, Frangioni JV, Tsuda A. Rapid Translocation of Nanoparticles from the Lung Airspaces to the Body. Nature Biotechnology, 28(12):1300-1303, 2010.
Lee GS, Filipovic N, Miele LF, Lin M, Collings-Simpson D, Gibney B, Konerding MA, Tsuda A, Mentzer SJ. Intravascular Pillars and Pruning in the Extraembryonic Vessels of Chick Embryos. Developmental Dynamics. 240(6):1335-1343, 2011.
Butler JP, Tsuda A. Transport of gases between the environment and alveoli – theoretical considerations. In: Comprehensive Physiology, Respiratory Physiology Section. J. Fredberg, G. Sieck, and W. Gerthoffer, eds. Amer. Physiol. Soc., 1(3):1301-1316, 2011.
Tsuda A, Henry FS, Butler JP. Particle transport and deposition. In: Comprehensive Physiology, Respiratory Physiology Section. J. Fredberg, G. Sieck, and W. Gerthoffer, eds. Amer. Physiol. Soc., 2011. (in press)
Gibney B, Lee GS, Houdeck J, Lin M, Miele L, Chamoto K, Konerding MA, Tsuda A, Mentzer SJ. Dynamic determination of oxygenation and lung compliance in murine pneumonectomy. Exp. Lung Res. 37(5):301-309, 2011.
Lin M, Chamoto K, Gibney B, Lee GS, Simpson DC, Houdeck J, Konerding MA, Tsuda A, Mentzer SJ. Angiogenesis Gene Expression in Murine Endothelial Cells During Post-Pneumonectomy Lung Growth. Respir. Research. 12(1):98, 2011.
Kojic M, Butler JP, Vlastelica I, Stojanovic B, Rankovic V, Tsuda A. Geometric Hysteresis of Alveolated Ductal Architecture. ASME J. Biomech. Eng. 133(11):111005, 2011.
Tsuda A, Laine-Pearson FE, Hydon PE. Why Chaotic mixing of particles is inevitable in the deep lung. J. Theor. Biol. 286:57-66, 2011.
Chamoto K, Gibney BC, Lee GS, Lin M, Collings-Simpson D, Voswinckel R, Konerding MA, Tsuda A, Mentzer SJ. CD34+ Progenitor to Endothelial Cell Transition in Post-Pneumonectomy Angiogenesis. Am J Respir Cell Mol Biol. 46(3):283-289. 2012.
Konerding MA, Gibney BC, Houdek JP, Chamoto K, Ackermann M, Lee GS, Lin M, Tsuda A, Mentzer SJ. Spatial dependence of alveolar angiogenesis in post-pneumonectomy lung growth. Angiogenesis. 15(1):23-32, 2012.
Schulz H, Eder G, Bolle I, Tsuda A, Karrasch S. Micron-sized intrapulmonary particle deposition in the developing rat lung. J. Appl. Physiol. 112(5):759-765, 2012.
Semmler-Behnke M, Kreyling WG, Schulz H, Takenaka S, Butler JP, Henry FS, Tsuda A. Nanoparticle Delivery in Infant Lungs. Proc. Natl. Acad. Sci. USA. 109(13):5092-5097, 2012.
Butler J, Loring SH, Patz S, Tsuda A, Yablonskiy DA, Mentzer SJ. Evidence for adult lung growth in humans. N. Engl. J. Med. 2012. (in press)
- BSME (1979), Kyoto University of Industrial Arts, Japan
- MS (1982), Ph.D. (1986), Worcester Polytechnic Institute