Objectives: The living world is embedded in the physical world. Small organisms live in a world of diffusion. The rest of us require a system of ducts for transport of all the materials we need to live. Systems of branched ducts are found in lung, kidney, mammary gland, and many other organs. This project's primary objective is to understand the mechanisms of tissue dynamics that create branched systems. It also aims to clarify the best ways to work with continuum mechanical models of morphogenesis to realistically describe mechanics and transport in developing tissues. Additionally, the project will develop new numerical methods for mixture models with interfaces. We will then test these models in a real time living branching system, the early embryonic lung.
Aim 1 : Develop accurate, stable, efficient methods for solving mixture problems with sharp interfaces.
Aim 2 : Develop a suite of models of the mechanical aspects of branching epithelia.

Public Health Relevance

Branching morphogenesis is essential for the construction/reconstruction of our bodies. The insights gained from this collaboration will inform our understanding of normal and abnormal development of the lung and other organs. Many of the methods developed will be adaptable to other problems in the dynamics of cells and tissues, in development, cancer, wound healing, angiogenesis, and other areas.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZGM1-CBCB-5 (BM))
Program Officer
Hoodbhoy, Tanya
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
North Carolina State University Raleigh
Biostatistics & Other Math Sci
Schools of Arts and Sciences
United States
Zip Code
Song, Peng; Xue, Jianping; Li, Zhilin (2013) Simulation of longitudinal exposure data with variance-covariance structures based on mixed models. Risk Anal 33:469-79
Li, Zhilin; Song, Peng (2013) Adaptive mesh refinement techniques for the immersed interface method applied to flow problems. Comput Struct 122:249-258
Warburton, David; Shi, Wei; Xu, Bing (2013) TGF-*-Smad3 signaling in emphysema and pulmonary fibrosis: an epigenetic aberration of normal development? Am J Physiol Lung Cell Mol Physiol 304:L83-5
Al Alam, Denise; Warburton, David (2013) Wingless: developmentally important genes that respond adversely to smoking. Thorax 68:703-4
Lozoya, Oswaldo A; Lubkin, Sharon R (2012) Mechanical control of spheroid growth: distinct morphogenetic regimes. J Biomech 45:319-25
El-Hashash, Ahmed H K; Al Alam, Denise; Turcatel, Gianluca et al. (2011) Six1 transcription factor is critical for coordination of epithelial, mesenchymal and vascular morphogenesis in the mammalian lung. Dev Biol 353:242-58
Lozoya, Oswaldo A; Wauthier, Eliane; Turner, Rachael A et al. (2011) Regulation of hepatic stem/progenitor phenotype by microenvironment stiffness in hydrogel models of the human liver stem cell niche. Biomaterials 32:7389-402
El-Hashash, Ahmed H; Warburton, David (2011) Cell polarity and spindle orientation in the distal epithelium of embryonic lung. Dev Dyn 240:441-5
El-Hashash, Ahmed H K; Turcatel, Gianluca; Al Alam, Denise et al. (2011) Eya1 controls cell polarity, spindle orientation, cell fate and Notch signaling in distal embryonic lung epithelium. Development 138:1395-407
Jackson, Sha-Ron; Lee, Jooeun; Reddy, Raghava et al. (2011) Partial pneumonectomy of telomerase null mice carrying shortened telomeres initiates cell growth arrest resulting in a limited compensatory growth response. Am J Physiol Lung Cell Mol Physiol 300:L898-909

Showing the most recent 10 out of 12 publications