Biomedical Engineering Site Menu
Distinguished Professor and Department Head
233 Hallowell Building
University Park, PA 16802
Phone: 814-865-8091 / Fax: 814-863-0490
Personal Website: http://www.bioe.psu.edu/labs/Dong-Lab/cellmech.htm
Ph.D. Applied Mechanics and Bioengineering, Columbia University, 1988
The major focus of Dr. Dong's research is to elucidate biomechanical, biophysical and biochemical aspects of cellular function in the circulatory systems, with particular interest in cellular biomechanics, cell adhesion, cell migration, cell signaling, systems biology, and multi-scale modeling of biological systems. Current research in the Cellular Biomechanics Laboratory at Penn State University includes studies of micro-hemodynamics, leukocyte rheology, intercellular and intracellular signaling, cancer immunology and metastases. In particular, he is investigating how fluid dynamics, adhesion kinetics and tumor microenvironment change leukocyte and/or endothelial immune functions which subsequently affect tumor cell extravasation in the microcirculation and subsequent metastasis. Research projects have been sponsored by the Whitaker Foundation, the American Cancer Society, the National Science Foundation, and the National Institutes of Health.
Most current research focuses on tumor cell extravasation. Extravasation is a process that involves active tumor cell adhesion to the endothelium under flow conditions and subsequent transendothelial migration toward extracellular matrix. The interactions between cancer cells and the host immune system are of particular interest to the Laboratory that studies potential mechanisms that link cancer and inflammation. White blood cells, neutrophils (PMN) in particular, are being studied to better understand how the host immune system affects cancer cell adhesion and subsequent migration in within a tumor microenvironment. A novel in vitro extravasation chamber system has been recently developed by the Laboratory, where shear flow can be introduced over the endothelial substrate affecting tumor cell adhesion and transmigration. It has been found that transmigration of melanoma cells under flow conditions can be influenced by those tumor-elicited circulating PMNs and mediated by altered inflammatory cytokines secreted within the tumor microenvironment, which further enhance tumor-endothelium adhesive interactions and subsequent endothelial junction disassembly; hence the metastasis. (Slattery and Dong, 2003; Slattery et al. 2005; Liang et al. 2005/2007/2008; Peng et al. 2005/2007/2009; Dong and Robertson 2009; Khanna et al. 2010)
Studies were also conducted on tumor cell protrusion and locomotion in response to a chemotactic signal in terms of the tumor cell motility. Cancer metastasis relies upon mechanisms similar to leukocyte motility as cell emigrates through the endothelial barrier during the inflammatory process, including pseudopod formation, cell shape change, and subsequent cell locomotion. In response to a chemotactic signal, tumor cell locomotion is modulated by the cytoskeleton remodeling dynamics, characterized by calcium and small GTP protein-mediated events. Using cultured melanoma cell lines as models, the micropipette techniques and migration assays have been used to uncover the molecular mechanisms responsible for tumor cell locomotion. (Dong et al. 1994; You et al. 1995/1996/1999; Hodgson et al. 2000/2001/2003)
Other projects involved studies on behavior of human leukocyte-endothelium interactions in light of its important role in the inflammatory process and in the development of artificial organs associated with prolonged blood contact. The process of leukocyte-surface interaction revolves around a complex balance of forces arising from hemodynamic shearing effect and the strength of adhesive bonds between cells and their substrate. This balance depends strongly on cell deformability and the expression of cell adhesion molecules (CAMs). In the course of these studies, a novel side-view flow chamber system has been developed to examine leukocyte deformation and adhesion to various surfaces (e.g., cultured vascular endothelium, reconstituted purified CAMs, or biomaterial) under flow conditions that simulate an in vivo environment. (Cao et al. 1997/1998; Lei et al. 1999; Dong et al. 1999/2000; Leyton-Mange et al. 2006)
The Cellular Biomechanics Laboratory is equipped with two tissue culture hoods; a double-deck CO2 incubator; a -80C and a -20C freezer; a liquid N2 storage tank; a 4C media storage refrigerator; three inverted microscopes (equipped respectively with capabilities on multi-channel fluorescence, DIC, phase contrast, and real-time video); a Cooke pco-1600 high-speed/sensitivity digital CCD camera; a TSI PIVCAM (PIV camera); a Nd-YAG 532 nm laser system for micro-PIV applications; a Photometrics CoolSNAP EZ high-resolution low-light color CCD camera; a Dage intensified system; protein analysis systems (including: a Bio-Rad spectrophotometer plate reader; vertical electrophoresis and blotting equipment; a bench-top multi-channel Guava PCA flow cytometer; an HAAKE cone-plate viscometer). 7 high-speed PCs are available in the Laboratory for data analyses and simulations. Two PCs are equipped with frame grabber boards (real-time data acquisition) and imaging processing capabilities. One high-speed computer is linked to the digital calcium and FRET imaging and processing system; while the other high-speed computer is linked to the micro-PIV imaging and CFD simulations. The Laboratory space is about 1200 square feet (3 rooms) located on the third floor of the Hallowell Building at Penn State University, University Park campus.
(16 representative and recent articles)
- Khanna, P., Chung, C-Y., Neves, R., Robertson, G., Dong, C. 2013. CD82/KAI expression prevents IL-8-mediatedendothelial gap formation in late-stage melanomas. Oncegene doi:10.1038/onc.2013.249.
- Zhang, P., Ozdemir, T., Chung, C.-Y., Robertson, G.P. and Dong, C. 2011. Sequential binding of αvβ3 and ICAM-1 determines fibrin-mediated melanoma capture and stable adhesion to CD11b/CD18 on neutrophil. J. Immunology 186: 242-254.
- Huh, S.J., Liang, S., Dong, C. and Robertson, G.P. 2010. Transiently entrapped circulating tumor cells interact with neutrophils to facilitate lung metastasis development. Cancer Res. 70: 6071-6082.
- Khanna, P., Yunkunis, T., Muddana, H., Peng, H.H., August, A. and Dong, C. 2010. p38 MAP Kinase is necessary for melanoma-mediated regulation of VE-cadherin disassembly. Am. J. Physiol - Cell Physiol. 298: C1140-50.
- Peng, H.H. and Dong, C. 2009. Systemic analysis of tumor cell-induced endothelial calcium signaling and junction disassembly. Cellular and Molecular Bioengineering 2(3): 375-385.
- Liang, S., Hoskins, M.H., Khanna, P., Kunz, R.F. and Dong, C. 2008. Effects of the tumor-leukocyte microenvironment on melanoma-neutrophil adhesion to the endothelium in a shear flow. Cellular and Molecular Bioengineering 1: 189-200.
- Liang, S., Slattery, M., Wagner, D., Simon,S.I., and Dong, C., 2008. Hydrodynamic shear rate regulates melanoma-leukocyte aggregations, melanoma adhesion to the endothelium and subsequent extravasation. Ann. Biomed. Eng. 36: 661-671.
- Liang, S., Sharma, A., Peng, H.H., Robertson, G. and Dong C. 2007. Targeting mutant (V600E) B-raf in melanoma disrupts immunoediting of leukocyte functions and melanoma extravasation. Cancer Research 67: 5814-5820.
- Peng, H.H., Liang, S., Henderson, A.J. and Dong, C. 2007. Regulation of interleukin-8 expression in melanoma-stimulated neutrophil inflammatory response. Experimental Cell Research 313: 551-559.
- Leyton-Mange, J., Sung, Y., Henty, M., Kunz, R.F., Zahn, J., and Dong, C. 2006. Design of a side-view particle imaging velocimetry flow system for cell-substrate adhesion studies. ASME - J. Biomech. Eng. 128: 271-278.
- Liang, S., Slattery, M., and Dong C. 2005. Shear stress and shear rate differentially affect the multi-step process of leukocyte-facilitated melanoma adhesion. Experimental Cell Research 310: 282-292.
- Peng, H.H., Hodgson, L., Henderson, A.J., and Dong, C. 2005. Involvement of phospholipase C signaling in melanoma cell-induced endothelial junction disassembly. Frontiers in Bioscience 10: 1597-1606.
- Slattery, M., Liang, S. and Dong, C. 2005. Distinct role of hydrodynamic shear in PMN-facilitated melanoma cell extravasation. Am. J. Physiol. 288 (4): C831-839.
- Hodgson, L., Henderson, A.J., and Dong, C. 2003. Melanoma cell migration to type IV collagen requires activation of NF-kappaB. Oncogene 22: 98-108.
- Dong, C., Cao, J. Struble, E. and Lipowsky, H.H. 1999. Mechanics of leukocyte deformation and adhesion to endothelium in shear flow. Ann. Biomed. Eng.27: 298-312.
- Cao, J., Donell, B., Deaver, D.R., Lawrence, M.B. and Dong, C. 1998. In vitro side-view technique and analysis of human T-leukemic cell adhesion to ICAM-1 in shear flow. Microvasc. Res. 55: 124-137.