Research Interests:

Our laboratory is interested in the question of how microenvironmental cues, including extracellular matrix (ECM) and mechanical forces, regulate cellular signal transduction and thereby control tissue morphogenesis. Our work includes analysis of integrin signaling, cytoskeletal organization, cellular mechanics, mechanotransduction, as well as development of new approaches to tissue engineering and angiogenesis inhibition. Our work has revealed that given the same set of chemical inputs, ECM and mechanical deformation of cells (shape changes) can regulate their functional output by switching cells between gene programs for growth, differentation, apoptosis, contractility, and motility. By combining methods of molecular cell biology with engineering and computational approaches, we have discovered that this mechanism involves activation of integrin signaling pathways as well as mechanical stress-induced changes in cell, cytoskeletal, and nuclear structure. We are currently carrying out studies using capillary endothelial cells, smooth muscle cells, fibroblasts and embryonic lung rudiments to more precisely map out the series of molecular and biophysical events that mediate these effects. We also are using massively-parallel, genome-wide gene profiling techniques and developing new bioinformatics tools to understand how these structural networks control cell fate switching. Results of these studies should have widespread implications for control of tissue physiology and may facilitate the development of new therapeutic modalities for diseases, such as hypertension and cancer, as well as novel approaches for tissue engineering.

Selected Publications:

Mannix, R.J., Kumar, S., Cassiola, F., Montoya-Zavala, M., Feinstein, E., Prentiss, M., and Ingber, D.E. (2008) Nanomagnetic actuation of receptor-mediated signal transduction. Nature Nanotechnol. 3(1): 36-40.

Ghosh, K., Thodeti, C.K., Dudley, A.C., Mammoto, A., Klagsbrun, M., and Ingber, D.E. (2008) Tumor-derived endothelial cells exhibit aberrant Rho-mediated mechanosensing and abnormal angiogenesis in vitro. Proc. Natl. Acad. Sci. USA 105(32): 11305-10.

Chang, H.H., Hemberg, M., Barahona, M., Ingber, D.E., and Huang, S. (2008) Transcriptome-wide noise controls lineage choice in mammalian progenitor cells. Nature 453(7194): 544-7.

Xia, N., Thodeti, C.K., Hunt, T.P., Xu, Q., Ho, M., Whitesides, G.M., Westervelt, R., and Ingber, D.E. (2008) Directional control of cell motility through focal adhesion positioning and spatial control of Rac activation. FASEB J. 22(6): 1649-59.