In this revised application we propose to bridge cutting-edge topics in biology and physics in order to create a new physical picture of collective cellular migration in lung health and disease. The projects and cores of this program focus upon a common central hypothesis: In collective behaviors of epithelial cells in the lung, di- verse physical factors and their multiple biological effects are brought together by the concept of the glass transition as described on a unifying jamming phase diagram. Each project director is a leader in his or her respective discipline. Project 1 (Weitz) will investigate basic physics at the level of the single cell in isolation (0-D), in single-file migration (1-D), and in transition to 2-D behavior. This project will emphasize the unifying role of cell volume regulation in mechanical determinants of cell jamming. Project 2 (Fredberg) will investigate basic physics of jamming in monolayers (2-D) and cell clusters (3-D). Project 3 (Drazen) will investigate the role of jamming in the bronchial epithelium as a basic mechanisms of asthma pathogenesis. Core A (Butler, Zaman, Krishnan) will support and develop novel technologies for imaging of physical forces. Core B (Weiss) will seek common molecular network motifs that span projects and characterize regions of the jamming phase diagram. Core C (Fredberg) is administrative. Together, the interdisciplinary projects and cores of this pro- gram project combine physics and biology at a level that is realized only rarely. The projects are unified by a central hypothesis that is radical, mechanistic and testable, and that has the potential to impact basic under- standing of lung injury and repair.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
Project #
Application #
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Harvard University
United States
Zip Code
Hiorns, Jonathan E; Bidan, Cécile M; Jensen, Oliver E et al. (2017) Corrigendum: Airway and Parenchymal Strains during Bronchoconstriction in the Precision Cut Lung Slice. Front Physiol 8:117
Habib, Naomi; Avraham-Davidi, Inbal; Basu, Anindita et al. (2017) Massively parallel single-nucleus RNA-seq with DroNc-seq. Nat Methods 14:955-958
Faiz, A; Donovan, C; Nieuwenhuis, M Ae et al. (2017) Latrophilin receptors: novel bronchodilator targets in asthma. Thorax 72:74-82
Bhatawadekar, Swati A; Inman, Mark D; Fredberg, Jeffrey J et al. (2017) Contribution of rostral fluid shift to intrathoracic airway narrowing in asthma. J Appl Physiol (1985) 122:809-816
Weiss, Scott T (2017) Emerging mechanisms and novel targets in allergic inflammation and asthma. Genome Med 9:107
Jang, Hwanseok; Notbohm, Jacob; Gweon, Bomi et al. (2017) Homogenizing cellular tension by hepatocyte growth factor in expanding epithelial monolayer. Sci Rep 8:45844
Rosner, Sonia R; Pascoe, Christopher D; Blankman, Elizabeth et al. (2017) The actin regulator zyxin reinforces airway smooth muscle and accumulates in airways of fatal asthmatics. PLoS One 12:e0171728
O'Sullivan, Michael J; Gabriel, Elizabeth; Panariti, Alice et al. (2017) Epithelial Cells Induce a Cyclo-Oxygenase-1-Dependent Endogenous Reduction in Airway Smooth Muscle Contractile Phenotype. Am J Respir Cell Mol Biol 57:683-691
Prakadan, Sanjay M; Shalek, Alex K; Weitz, David A (2017) Scaling by shrinking: empowering single-cell 'omics' with microfluidic devices. Nat Rev Genet 18:345-361
Rodríguez-Franco, Pilar; Brugués, Agustí; Marín-Llauradó, Ariadna et al. (2017) Long-lived force patterns and deformation waves at repulsive epithelial boundaries. Nat Mater 16:1029-1037

Showing the most recent 10 out of 40 publications