Donald E. Ingber, M.D., Ph.D.
Judah Folkman Professor of Vascular Biology
Department of Pathology, HMS
Professor of Bioengineering, Harvard School of Engineering and Applied Sciences
Senior Member, Vascular Biology Program, Departments of Surgery & Pathology, Children’s Hospital
Director, Wyss Institute for Biologically Inspired Engineering at Harvard University
Karp Family Research Laboratories, 11.127
300 Longwood Avenue
Boston, MA 02115
Tel: (617) 919-2223
Fax: (617) 730-0230
12 postdoctoral fellows, 3 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 tissue morphogenesis. Once we uncover fundamental biological design principles, we design and engineer new materials and devices that mimic these complex functionalities for medical and non-medical applications. 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 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 approaches for tissue engineering.
- Mammoto A, Connor K, Mammoto T, Aderman C, Mostoslavsky G, Smith LEH and Ingber DE. A mechanosensitive transcriptional control mechanism that controls angiogenesis. Nature 2009; 457:1103-1108.
- 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 vitro. Proc. Natl. Acad. Sci. U. S. A. 2008 32: 11305-11310.
- Yung C , Ingber DE. Micromagnetic – Microfluidic Blood Cleansing Microdevice. Lab on a Chip 2009; DOI: 10.1039/b816986a.
BBS webpage updated 12/02/2009