Donald E. Ingber, M.D., Ph.D.

Judah Folkman Professor of Vascular Biology
Department of Pathology, HMS
Vascular Biology Program, Children's Hospital
Karp Family Research Laboratories, 11.127
300 Longwood Avenue
Boston, MA 02115
Tel: (617) 919-2223
Fax: (617) 730-0230
Email: donald.ingber@childrens.harvard.edu
11 postdoctoral fellows, 4 graduate students

My laboratory is interested in the question of how microenvironmental cues, including extracellular matrix (ECM) and mechanical forces, regulate cellular signal transduction and thereby control cell fate switching during 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, nanotechnology, engineering, physics 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 that impact cell regulatory networks at the genome-wide level. We are currently carrying out studies using capillary endothelial cells, smooth muscle cells, fibroblasts, embryonic organ rudiments and transgenic cancer models 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 cellular information processing. 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 biologically inspired approaches for tissue engineering, therapeutics and robotics.

References:

• Chang H, Hemberg M, Barahona M, Ingber DE and Huang S. Transcriptome-wide noise controls lineage choice in mammalian progenitor cells. Nature. 2008; 453: 544-547.
• Ghosh K, Thodeti CK, Dudley D, Mammoto A, Klagsbrun M, and Ingber DE. Tumor derived endothelial cells exhibit aberrant Rho-mediated mechanosensing and abnormal angiogenesis in vivo. Proc. Natl. Acad. Sci. U. S. A. – in press.
• Ingber DE. Can cancer be reversed by engineering the tumor microenvironment? Semin Cancer Biol. 2008 Apr 1 [Epub ahead of print].