Ning Wang, Ph.D.
Leonard C and Mary Lou Hoeft Endowed Professor in Engineering
Department of Mechanical Science and Engineering
University of Illinois at Urbana-Champaign (UIUC)
Seminar Information
Mechanical forces influence almost every aspect of cells and tissues but the mechanisms of force-induced gene expression remain poorly understood. We have discovered that chromatin is a mechanosensor and that chromatin is stretched milliseconds after application of a local cell surface stress via integrins, CSK, and LINC complexes. The extent of transgene DHFR (dihydrofolate reductase) rapid upregulation depends on the degree of chromatin stretching. Recently we have extended these findings on force-induced rapid upregulation to endogenous genes egr-1 (early growth response-1) and Cav1 (caveolin-1), suggesting the force acts like a “super transcription factor”. We reveal that prestressed actin bundle anisotropy determines long-distance force propagation, the extent of chromatin stretching, and ensuing gene upregulation. We show that rapid gene upregulation depends on chromatin stretching but not compression. We have identified BAF and LAP2β as the nuclear proteins responsible for force transmission from nuclear lamina to chromatin to stretch chromatin domains and to activate genes via recruitments of RNA polymerase II to the promoter sites of demethylated H3K9me3. We have found that demethylated H3K9me3 leads to upregulation of self-renewal gene Sox2 in tumor repopulating cells. Together with our published evidence that cell softness and low CSK prestress play a central role in proliferation and metastasis of malignant tumor repopulating cells, we propose a mechanobiology model of tumor cell softness for tumor progression and dormancy that depends on relative stiffness of tumor cells and their extracellular matrices.
Professor Ning Wang is the Leonard C and Mary Lou Hoeft Endowed Professor in Engineering in the Department of Mechanical Science and Engineering at University of Illinois at Urbana-Champaign (UIUC). Professor Wang joined the faculty at UIUC in 2006 after being a faculty member at Harvard University School of Public Health for over a decade. Professor Wang conducts research in the areas of cell mechanics, mechanotransduction, mechanobiology, and mechanomedicine using novel experimental technologies and theoretical analyses.
Professor Wang and colleagues invented the Magnetic Twisting Cytometry (MTC) technology for probing a single cell’s mechanical properties and discovered in 1993 that the cell-matrix adhesion molecules-integrins are mechanosensors, spurring the emergence of cellular mechanobiology. He provided first experimental evidence that endogenous cytoskeletal prestress regulates cell shear stiffness and controls gene expression in early 2000’s. Wang’s laboratory discovered stress focusing and the long-distance force propagation in live cells and demonstrated fundamental differences between mechanical force-based signaling and soluble growth factor-based signaling. Professor Wang discovered that an embryonic stem cell differentiates in response to applied forces of physiological magnitudes. Wang’s lab has developed a novel mechanical method that selects a small subpopulation of malignant tumor cells (called tumor-repopulating cells) that are highly efficient in metastasis. In recent years Wang’s lab discovered that gene expression can be directly upregulated by stretching the chromatin via applying forces to integrins in a living cell and revealed that the force-induced gene activation depends on histone modifications of the chromatin.
Ning Wang received American Physiological Society Scholander Award in 1991 for his contribution to comparative physiology. Wang holds Doctor of Science degree in Physiology from Harvard University and M.S. in biomedical engineering and B.S. in biomechanics from Huazhong University of Science and Technology in China.