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Welcome to the Haller Lab: RESPIRATORY CELL PHYSIOLOGY

Our research focuses on the regulation of surfactant secretion by type II pneumocytes, the significance and biophysical properties of surfactant at the respiratory interface, and alveolar epithelial cell physiology in general (P. Dietl and T. Haller, 2005: Annu. Rev. Physiol. 67: 595-621). 

 

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Specifically, we are interested in:

 
  • Cellular mechanisms of exocytosis (e.g. T. Haller, J. Ortmayr, F. Friedrich, H. Völkl, P. Dietl, 1998: Proc. Natl. Acad. Sci. USA 95: 1579-1584)
   
 
  • Fusion pore characteristics and surfactant extrusion (e.g. T. Haller, P. Dietl, K. Pfaller, M. Frick, N. Mair, M. Paulmichl, M.W. Hess, J. Fürst, K. Maly, 2001:J. Cell Biol. 155: 279-289)
 
  • Stimulus-secretion coupling and the role of Ca2+-stores and -signals (e.g. T. Haller, K. Auktor, M. Frick, N. Mair, P. Dietl, 1999: Am. J. Physiol. Lung Cell. Mol. Physiol. 277:L893-L900)
 
  • Cell mechanics and tissue stretch (e.g. W. Singer, M. Frick, T. Haller, S. Bernet, M. Ritsch-Marte, P. Dietl, 2003: Biophys. J. 84: 1344-1351)
 
  • Ion channels and mechanoreceptive elements (e.g. M. Frick, C. Bertocchi, P. Jennings, T. Haller, N. Mair, W. Singer, W. Pfaller, M. Ritsch-Marte, P. Dietl, 2004: Am. J. Physiol. Lung Cell. Mol. Physiol. 286: L210-220)
 
  • Growth factors, cytokines and immunomodulatory substances (e.g. I. Garcia-Verdugo, A. Ravasio, E. Garcia de Paco, M. Synguelakis, N. Ivanova, J. Kanellopoulos, T. Haller, 2008: Am. J. Physiol. Lung Cell. Mol. Physiol.295: L708-717)
 
  • Interactions of cells with air-liquid-interfaces (e.g. N. Hobi, A. Ravasio, T. Haller, 2012: Am. J. Physiol. Lung Cell. Mol. Physiol. 303: L117-L129)
 
  • Experimental simulations of the alveolar microenvironment (A. Ravasio, N. Hobi, C. Bertocchi, A. Jesacher, P. Dietl, T. Haller, 2011: Am. J. Physiol. Cell Physiol. 300: C1456-C1465)
 
  • Lamellar body adsorption kinetics and surface film formation (e.g. N. Hobi, G. Siber, V. Bouzas, A. Ravasio, J. Pérez-Gil, T. Haller, 2014: Biochim. Biophys. Acta 1838: 1842-1850)
 
  • Stem cells (A. Cerrada, P. de la Torre, J. Grande, T. Haller, A. Flores, J. Pérez-Gil 2014: PLOS one. Oct 15;9(10):e110195. doi: 10.1371/journal.pone.0110195)
 
  • Toxicology and nanotoxicology (e.g. V. Bouzas, T. Haller, N. Hobi, E. Felder, I. Pastoriza-Santos, J. Pérez-Gil, 2014: Nanotoxicol. 8: 813-823)
 
  • Bioassays for functional cell studies (e.g. A. Wemhöner, M. Frick, P. Dietl, P. Jennings, T. Haller, 2006: J. Biomol. Screen. 11: 286-295)
 
  • Methodological innovations (e.g. C. Bertocchi, A. Ravasio, S. Bernet, G. Putz, P. Dietl, T. Haller, 2005: Biophys. J. 89: 1353-61)

 

 Techniques


 

„The bricoleur… is someone who uses the means at hand, that is, the instruments he finds at his disposition around him, those which are already there… for an operation for which one tries by trial and error to adapt them, not hesitating to change them whenever it appears necessary”

Jacques Derrida about the bricoleur in Claude Lévi-Strauss: The Savage Mind

Our ‘Bricolage’ is essentially based on standard laboratory methods with an accent on primary cell culture and fluorescent microscopy. Though, we are constantly in search of innovative strategies to tackle the problems associated with the lung’s complex microenvironment, not only comprising oscillating tissue stretch and strain but tensile forces acting on the highly curved and dynamic air-liquid interfaces and transmitted to the cells. So, for example, we have introduced:

 

  • a modified Du Noüy vertical pull surface tension technique (T. Haller et al. Am. J. Physiol. Lung Cell. Mol. Physiol. 286: L1009-1015, 2004)
  • a non-invasive optical surface tensiometry (C. Bertocchi et al. Biophys. J. 89: 1353-61, 2005)
  • a miniaturized inverted air-liquid interface device (T. Haller et al. Am. J. Physiol. Lung Cell. Mol. Physiol. 286: L1009-1015, 2004)
  • a fluorescence microplate-based exocytosis assay (A. Wemhöner et al. J. Biomol. Screen. 11: 286-295, 2006)
  • a high throughput lipid adsorption assay (Ravasio et al. J. Lipid Res. 49: 2479-88, 2008)
  • an equibiaxial cell-strain device (M. Frick et al. Am. J. Physiol. Lung Cell. Mol. Physiol. 286: L210-220, 2004)

 

For very specific problems we used e.g. optical tweezers and interferometry, a self-made flash photolysis setup, captive bubble and Wilhelmy surface balance measurements beside some other, non-routine technologies. Currently, we are also exploiting the possibilities of CARS and polarization microscopy, correlative and functionalized AFM and EDX-spectroscopy and are working on the refinement of cell culture conditions to better simulate all aspects of the alveolar condition.

 

Collaborations

University of Ulm, Institute of General Physiology https://www.uni-ulm.de/

Universidad Complutense Madrid, Department of Biochemistry http://www.bbm1.ucm.es/public_html/

 

Latest Publications

 

2018: Polarized light microscopy reveals physiological and drug-induced changes in surfactant membrane assembly in alveolar type II pneumocytes. Haller, T., Cerrada, A., Pfaller, K., Braubach, P., Felder, E. BBA-Molecular Cell Research. http://www.ncbi.nlm.nih.gov/pubmed/29317199

2016: A small key unlocks a heavy door: The essential function of the small hydrophobic proteins SP-B and SP-C to trigger adsorption of pulmonary surfactant lamellar bodies. Hobi, N., Giolai, M., Olmeda, B., Miklavc, P., Felder, E., Walther, P., Dietl, P., Frick, M., Perez-Gil, J., Haller, T. BBA-Molecular Cell Research. http://www.ncbi.nlm.nih.gov/pubmed/27155084

2015: Pneumocytes assemble lung surfactant as highly packed/dehydrated states with optimal surface activity. Cerrada, A., Haller, T., Cruz, A., Perez-Gil, J. Biophy. J. 109: 2295-2306. https://www.ncbi.nlm.nih.gov/pubmed/26636941

2015: A new role for an old drug: Ambroxol triggers lysosomal exocytosis via pH-dependent Ca2+-release from acidic Ca2+-stores. Fois, G., Hobi, N., Felder, E., Ziegler, A., Miklavc, P., Walther P., Rademacher P., Haller, T., Dietl. P. Cell Calcium 58: 628-637. https://www.ncbi.nlm.nih.gov/pubmed/26560688

2014: Human Decidua-Derived Mesenchymal Stem Cells Differentiate into Functional Alveolar Type II-Like Cells that Synthesize and Secrete Pulmonary Surfactant Complexes. Cerrada,  A., de la Torre, P., Grande, J., Haller, T., Flores, AI., Pérez-Gil J. PLoS One. Oct 15;9(10):e110195. doi: 10.1371/journal.pone.0110195.  https://www.ncbi.nlm.nih.gov/pubmed/25333871

2014: Physiological variables affecting surface film formation by native Lamellar Body-like Pulmonary Surfactant Particles. Hobi, N., Siber, G., Bouzas, V., Ravasio, A., Perez-Gil, J., and Haller, T. Biochimica et biophysica acta. https://www.ncbi.nlm.nih.gov/pubmed/24582711

2014: Imaging the Stages of Exocytosis in Epithelial Type II Pneumocytes, Haller, T., and Dietl, P. Exocytosis Methods 83 (Humana Press), 23-37. 

2014: Nontoxic impact of PEG-coated gold nanospheres on functional pulmonary surfactant-secreting alveolar type II cells. Bouzas, V., Haller, T., Hobi, N., Felder, E., Pastoriza-Santos, I., and Perez-Gil, J. Nanotoxicology 8, 813-823

2012: Interfacial stress affects rat alveolar type II cell signaling and gene expression. Hobi, N., Ravasio, A., and Haller, T. American journal of physiology Lung cellular and molecular physiology 303, L117-129

2012: Spatio-temporal aspects, pathways and actions of Ca(2+) in surfactant secreting pulmonary alveolar type II pneumocytes. Dietl, P., Haller, T., and Frick, M. Cell calcium 52, 296-302

2011: Effect of exogenous surfactants on viability and DNA synthesis in A549, immortalized mouse type II and isolated rat alveolar type II cells. Wemhoner, A., Jennings, P., Haller, T., Rudiger, M., and Simbruner, G. BMC pulmonary medicine 11, 11

2011: Fusion-activated Ca2+ entry via vesicular P2X4 receptors promotes fusion pore opening and exocytotic content release in pneumocytes. Miklavc, P., Mair, N., Wittekindt, O.H., Haller, T., Dietl, P., Felder, E., Timmler, M., and Frick, M. Proceedings of the National Academy of Sciences of the United States of America 108, 14503-14508

2011: Interfacial sensing by alveolar type II cells: a new concept in lung physiology? Ravasio, A., Hobi, N., Bertocchi, C., Jesacher, A., Dietl, P., and Haller, T. American journal of physiology Cell physiology 300, C1456-1465

2010: Effects of perfluorocarbons on surfactant exocytosis and membrane properties in isolated alveolar type II cells. Wemhoner, A., Hackspiel, I., Hobi, N., Ravasio, A., Haller, T., and Rudiger, M. Respiratory research 11, 52

2010: Fusion-activated Ca(2+) entry: an "active zone" of elevated Ca(2+) during the postfusion stage of lamellar body exocytosis in rat type II pneumocytes. Miklavc, P., Frick, M., Wittekindt, O.H., Haller, T., and Dietl, P. PloS one 5, e10982

2010: Lamellar bodies form solid three-dimensional films at the respiratory air-liquid interface. Ravasio, A., Olmeda, B., Bertocchi, C., Haller, T., and Perez-Gil, J. The Journal of biological chemistry 285, 28174-28182

2010: Recent advances in alveolar biology: some new looks at the alveolar interface. Possmayer, F., Hall, S.B., Haller, T., Petersen, N.O., Zuo, Y.Y., Bernardino de la Serna, J., Postle, A.D., Veldhuizen, R.A., and Orgeig, S. Respiratory physiology & neurobiology 173 Suppl, S55-64

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