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Cheng Dong

Ph.D. Applied Mechanics and Bioengineering, Columbia University, 1988

Professor of Bioengineering and Engineering Science and Mechanics

Dept. of Bioengineering
233 Hallowell Bldg
Tel:814-865-8091
Fax:814-863-0490
Email:cxd23@psu.edu

Cellular Biomechanics Laboratory

The major focus of Dr. Dong's research is to elucidate biomechanical, biophysical and biochemical aspects of cellular function in the circulatory system. A dual approach is taken that involves a coordination of in vitro biological experiments and mathematical modeling of cellular behavior. Dr. Dong collaborates with biologists at the National Institutes of Health, the Colleges of Science and Medicine at Penn State. Current research in the Cellular Biomechanics Laboratory includes studies of cell deformability, cell adhesion, intercellular and intracellular signaling, and cell motility involved in human immune response and cancer 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 in the microcirculation in response to stimulation by soluble extracellular matrix (ECM) proteins. An extravasation process involves active tumor cell adhesion to the endothelium under flow conditions and subsequent transendothelial migration toward ECM. The interactions between cancer cells and the host immune system are of particular interest to our group.  Innate immune system processes can potentially promote tumor progression through inflammation dependant mechanisms.  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 metastasis. A novel in vitro flow-migration chamber system has been recently developed, where shear flow can be introduced over the cell-substrate interface affecting tumor cell extravasation. It has been found that transmigration of C8161 melanoma cells under flow conditions can be influenced by the circulating leukocytes, mediated by intercellular signaling and altered cytokine secretion within a tumor microenvironment, which enhances tumor-endothelium adhesive interactions and subsequent endothelial junction disassembly (Dong et al. 2002; Slattery and Dong, 2003; Slattery et al. 2005; Liang et al. 2005; Peng et al. 2005).

Studies are also conducted on tumor cell protrusion and locomotion in response to a chemotactic signal involved in tumor cell migration. 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 changes 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 (A2058 and C8161) as models, the micropipette techniques and migration assays are currently used to uncover the molecular mechanisms responsible for tumor cell locomotion (Dong et al.1994; You et al. 1995 & 1999; Hodgson et al. 2000, 2001 and 2003).

Other projects involve studies on behavior of human leukocyte-endothelium interaction 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; Dong et al.1999; Lei et al. 1999; Dong and Lei, 2000).

Representative Publications

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.

Wang, J., Slattery, M., Hoskins, M., Liang, S., Dong, C. and Du, Q. 2006. Monte Carlo simulation of heterotypic cell aggregation in nonlinear shear flow. Mathematical Biosciences and Engineering 3(4): 683-696.

Sharma, A., Tran, M.A., Liang, S., Sharma, A.K., Amin, S., Smith, C.D., Dong, C., and Robertson, G.P. 2006. Targeting Mek in the Mutant (V600E) B-Raf signaling cascade effectively inhibits melanoma lung metastases. Cancer Research 66(16): 8200-8209.

Hoskins, M.H. and Dong, C. 2006. Kinetics analysis of binding between melanoma cells and neutrophils. Molecular and Cellular Biomechanics 3(2): 79-87.

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. J. Biomech. Eng. 128: 271-278.

Dong, C. Slattery, M.J., Liang, S. and Peng, H.-H. 2005. Melanoma cell extravasation under flow conditions is modulated by leukocytes and endogenously produced interleukin 8. Molecular and Cellular Mechanics 2(3): 145-159.

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.

Slattery M, Liang S, and Dong C. 2005. Distinct role of hydrodynamic shear in leukocyte-facilitated tumor cell extravasation. Am. J. Physio: Cell Physio 288(4):C831-839.

Peng HH , Hodgson L, Henderson AJ, and Dong C. 2005. Involvement of phospholipase C signaling in melanoma cell-induced endothelial junction disassembly. Frontiers in Bioscience 10: 1597-1606.

Dong C, Slattery M, and Liang S. 2005. Micromechanics of tumor cell adhesion and migration under dynamic flow conditions. Frontiers in Bioscience 10: 379-384

Slattery, M. and Dong, C. 2003. Neutrophils influence melanoma adhesion and migration under flow conditions. 2003 Int’l J. Cancer, 106: 713-722.

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., Slattery, M.J., Rank, B.M., and You, J. 2002. In vitro characterization and micromechanics of tumor cell chemotactic protrusion, locomotion, and extravasation. Ann. Biomed. Eng. 30: 344-355.

Hodgson, L. and Dong, C. 2001. [Ca2+] as a potential down regulator of a2β1 integrin-mediated A2058 tumor cell migration to type IV collagen. Am. J. Physiol.- Cell Physiol. 281: C106-C113.

Hodgson, L., Qiu, W., Dong, C. and Henderson, A.J. 2001. Use of green fluorescent protein conjugated beta-actin as a novel molecular marker for in vitro tumor cell metastasis assay. Biotechnology Progress 16: 1106-1114.

Hodgson, L., Kohn, E.C. and Dong, C. 2000. Extracellular lipid-mediated signaling in tumor cell activation and pseudopod protrusion. Int’l J. Cancer 88: 593-600.

Dong, C. and Lei, X. 2000. Biomechanics of cell rolling: Shear flow, cell-surface adhesion, and cell deformability. J. Biomechanics 33: 35-43.

Lei, X., Lawrence, M.B. and Dong, C. 1999. Influence of cell deformation on leukocyte rolling adhesion in shear flow. J. Biomech. Eng.121: 636-643.

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.

You, J., Mastro, A.M. and Dong, C. 1999. Application of the dual micropipette technique to the measurement of tumor cell locomotion. Exp. Cell Research 248: 160-171.

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.

Cao, J., Usami, S. and Dong, C. 1997. Development of a side-view chamber for studying cell-surface adhesion under flow conditions. Ann. Biomed. Eng. 25: 573-580.

You, J., Aznavoorian, S., Liotta, L.A. and Dong, C. 1996. Responses of tumor cell pseudopod protrusion to changes in medium osmolality. J. Cellular Physiol. 167: 156-163.

You, J., Miele, M. E., Dong, C. and Welch, D. R. 1995. Suppression of human melanoma metastasis by introduction of chromosome 6 may be partially due to inhibition of motility but not invasion. J. Biochem. Biophys. Res. Comm. 208: 476-484.

Dong, C., You, J., Aznavoorian, S., Savarese, D. and Liotta, L.A. 1994. Actin polymerization and gel osmotic swelling in tumor cell pseudopod formation. Cell Mechanics and Cellular Engineering, Springer-Verlag, New York, pp. 515-533.

Dong, C., S. Aznavoorian, and Liotta, L. A., 1994. Two phases of pseudopod protrusion in tumor cells revealed by a micropipette. Microvasc. Res. 47: 55-67.

Dong, C., R. Skalak, and Sung, K.-L. P., 1991. Cytoplasmic rheology of passive neutrophils. Biorheology 28: 557-567.

Dong, C., R. Skalak, K.-L. P. Sung, G. W. Schmid-Schnbein, and S. Chien. Passive deformation analysis of human leukocytes. J Biomech Eng. 110: 27-36, 1988.

Sung, K.-L. P., Dong, C., Schmid-Schönbein, G. W., Chien, S., and Skalak, R. 1988. Leukocytes relaxation properties. Biophys. J. 54: 331-336.