Dr. George Plopper's Research Laboratory, Rensselaer Polytechnic Institute

General information.

Office: Center for Biotechnology and Interdisciplinary Studies (CBIS, aka the Biotech Building), room 2115.

Email: ploppg*at*rpi.edu

Office phone: (518) 276-8288. Fax: (518) 276-2851

From time to time, positions open up for new students in our laboratory. Interested students please check out the graduate or undergraduate prospective student information pages, as appropriate.

Current research projects.

Our laboratory is primarily concerned with determining how cellular adhesion to extracellular matrix (ECM) molecules elicits specific cellular responses, including growth, differentiation, and migration. We work human mesenchymal stem cells adhering to purified ECM proteins as our model system. Our general hypothesis is that adhesion to ECM molecules activates a subset of intracellular signaling pathways associated with integrin receptors, and that this signaling controls cell behaviors by modulating the organization of the cytoskeleton. Our research has both basic and applied elements, and is organized into two major projects:

	(1) Differentiation of human mesenchymal stem cells (hMSC) plated in/on defined ECM proteins: We are defining the effect of ECM contact on human mesenchymal stem cell differentiation. Our hypothesis is that contact with distinct ECM proteins stimulates specific integrin-associated signaling pathways that ultimately control the differentiation of these cells into bone-, cartilage-, or fat-producing cells. We are working with members of the Department of Biomedical Engineering on this project to investigate cellular response to a variety of extracellular stimuli. The project is subdivided into three subprojects, which are:(1) Encapsulation of hMSC in three-dimensional “beads” of defined ECM composition as a candidate delivery vehicle (working with Dr. Jan Stegemann at the University of Michigan), (2) Modeling of tissue formation using graph theoretical methods (with Dr. Bülent Yener in the Department of Computer Sciences), and (3) Identifying the role of key intracellular signaling pathways in controlling hMSC differentiation. Collectively, these studies should help us better understand the mechanisms governing hMSC differentiation and how to capitalize on this knowledge in tissue engineering applications.

National Institute of Arthritis and Musculoskeletal and Skin Diseases #1RO1 AR053231. Title: Defined microenvironments for controlling stem cell differentiation (Jan Stegemann, PI). August 2006-July 2010

National Institute or Biomedical Imaging and Bioengineering #1R01 EB008016. Title: Computational tool for closing the gap between tissue structure and function. July 1 2008-April 30 2012. $1,782,026.

1. Bradke, T., Hall, C., Carper, S., Plopper, G.E. Phenylboronic acid selectively inhibits human prostate and breast cancer cell migration and viability. Cell Adhesion and Migration, 2008 (In Press).

2. Yener, B., Acar, E., Agius, P., Vandenberg, S.L., Bennett , K.P.,and Plopper, G.E. Multiway modeling and analysis in stem cell systems biology. BMC-Systems Biology, Jul 14;2(1):63, 2008.

3. Bilgin, C.C., Bullough, P., Plopper, G.E., and Yener, B. ECM-Aware Cell-Graph Mining for Bone Tissue Modeling and Classification. Manuscript submitted, 2008.

4. Ward , D.F, Williams, W.A., Schapiro, N.E., Christy, S.R., Weber, G.L., Klees, R.F., Boskey, A., and Plopper, G.E. Focal adhesion kinase signaling controls cyclic tensile strain enhanced collagen I induced osteogenic differentiation of human mesenchymal stem cells. Molecular and Cellular Biomechanics, 4(4):177-188, 2007.

5. Lund, A., Stegemann, J.P., and Plopper, G.E. Inhibition of ERK Promotes Collagen Gel Compaction and Fibrillogenesis to Amplify the Osteogenesis of Human Mesenchymal Stem Cells in Three Dimensional, Collagen I Culture. Stem Cells and Development, 2008 (In Press)

6. Lund, A.W., Bush, J.A., Plopper, G.E. and Stegemann, J.P. Osteogenic Differentiation of Mesenchymal Stem Cells in Defined Protein Beads. Journal of Biomedical Materials Research (part B), 2008 (In Press).

7. Earley, S. and Plopper, G.E. Phosphorylation of Focal Adhesion Kinase Promotes Transendothelial Migration of Breast Cancer Cells. Biochemical and Biophysical Research Communications, 366(2): 476-482, 2008.

8. Klees, R.F., Salasznyk, R.M., Ward, D.F., Crone, D.E., Williams, W.A., Harris, M.A., Boskey, A., Quaranta, V., and Plopper, G.E. Dissection of the Osteogenic Effects of Ln-5 Utilizing Specific LG Domains: LG3 Induces Osteogenic Differentiation, but not Mineralization. Experimental Cell Research, Feb 15;314(4):763-73, 2008.

9. Bennett, K.P., Bergeron, C., Acar, E., Klees, R.F., Vandenberg, S.L., Yener, B., and Plopper, G.E. Multiple routes to the osteogenic phenotype in mesenchymal stem cells. BMC-Genomics, 8:380, 2007.

10. Ward, D.F., Salasznyk, R.M., Klees, R.F, Backiel, J., Boskey, A. and Plopper, G.E. Mechanical strain enhances ECM induced cell fate determination and promotes osteogenic differentiation of human mesenchymal stem cells through the ERK MAPK pathway. Stem Cells & Development, Jun;16(3):467-80, 2007.

11. Salasznyk, R.M., Klees, R.F, Vandenberg, S., Bennett, K, and Plopper, G.E. Laminin-5 activates extracellular matrix production and osteogenic gene focusing in human mesenchymal stem cells. Matrix Biology, Mar;26(2):106-14, 2007

12. Klees, R.F., Salasznyk, R.M., Boskey, A. and Plopper, G.E. Activation of FAK is necessary for the osteogenic differentiation of human mesenchymal stem cells on laminin-5. Journal of Cellular Biochemistry, Feb 1;100(2):499-514, 2007.

13. Salasznyk, R.M., Klees, R.F., Williams, W.A., Boskey, A, and Plopper, G.E. Focal adhesion kinase signaling pathways regulate the osteogenic differentiation of human mesenchymal stem cells. Experimental Cell Research, Jan 1;313(1):22-37, 2007.

14. Liu, H., Plopper, G., Earley, S., Chen, Y., Ferguson, B., and Zhang X.-C. Sensing minute changes in biological cell monolayers by THz differential time-domain spectroscopy. Biosensors and Bioelectronics, Jan 15;22(6):1075-80, 2007.

15. Plopper, G.E. Extracellular matrix and cell junctions. In: Cells, Lewin, B., Cassimeris, L., Lingappa, V.R., Plopper, G., editors. Jones & Bartlett, Sudbury MA, pp. 645-702, 2006.

16. Earley, S. and Plopper, G.E. Disruption of focal adhesion kinase slows transendothelial migration of AU-565 breast cancer cells. Biochemical and Biophysical Research Communications, Nov 17;350(2):405-12, 2006.

17. Klees, R.F., P.C. DeMarco, M. Hogg, D. Ahuja, Z.D. Lauria, L. Kamath, J.S. Dordick, and G.E. Plopper. Apocynin derivatives interrupt intracellular signaling resulting in decreased migration in breast cancer cells. Journal of Biomedicine and Biotechnology, 2006 (2006), Article ID 87246, 10 pages.

18. Williams, W.A., Schapiro, N.E., Christy, S.R., Weber, G.L., Salasznyk, R.M., and Plopper, G.E. Diminished Gene Expression in human Mesenchymal Stem Cells by Mutation of Focal Adhesion Kinase Signaling. Journal of Stem Cells, 1 (3): 173-182, 2006.

19. Kingsley, K, and G.E. Plopper. Laminin-5 modulates platelet-derived growth factor-stimulated mitogen-activated protein kinase responses in vitro. Cell Communication and Signaling, 3:2, 2005.

20. Klees, R.F., Salasznyk, R.M., Kingsley, K., Williams, W.A., Boskey, A. and Plopper, G.E. Laminin-5 induces osteogenic differentiation of human mesenchymal stem cells through an ERK dependent pathway. Molecular Biology of the Cell, 16:881-890, 2005.

21. Batorsky, A., Liao, J., Lund, A.W., Plopper, G.E., and Stegemann, J.P. Encapsulation of Adult Human Mesenchymal Stem Cells within Collagen-Agarose Microenvironments. Biotechnology and Bioengineering, 92(4):492-500, 2005.

22. Salasznyk, R.M., Klees, R.F, Vandenberg, S., Bennett, K, and Plopper, G.E. Gene focusing as a basis for controlling stem cell differentiation. Stem Cells and Development, 14:608-620, 2005.

23. Salasznyk, R.M., Westcott, A.M., Klees, R.F., Ward, D.F., Xiang, Z., Vandenberg, S., Bennett, K, and Plopper, G.E. Comparing the proteomes of human mesenchymal stem cells and human osteoblasts using gene ontologies. Stem Cells and Development, 14(4):354-66, 2005.

24. Salasznyk, R.M., Williams W.A., Boskey, A., Batorsky, A., and Plopper, G.E. Adhesion to Vitronectin and Collagen I Promotes Osteogenic Differentiation of Human Mesenchymal Stem Cells. Journal of Biomedicine and Biotechnology, 2004 (1): 24-34, 2004.

25. Salasznyk, R.M., Klees, R.F., Hughlock, M.K., and Plopper, G.E. ERK signaling pathways regulate the osteogenic differentiation of human mesenchymal stem cells on collagen I and vitronectin. Cell Communication and Adhesion, 11:137-153, 2004.

26. Kingsley, K., Rust, W.L., Huff, J.L., Smith, R.C., and Plopper, G.E. PDGF-BB enhances expression of, and reduces adhesion to, laminin-5 in vascular smooth muscle cells. Biochemical and Biophysical Research Communications, 294:1017-1022, 2002.

27. Kingsley, K., Huff, J.L., Rust, W.L., Carroll, K., Martinez, A.M., and Plopper, G.E. ERK1/2 activation mediates PDGF-BB stimulated vascular smooth muscle cell proliferation and migration on laminin-5. Biochemical and Biophysical Research Communications, 293:1000-1006, 2002.

28. Rust, W., Carper, S., and Plopper, G.E. The promise of integrins as effective targets for anti-cancer agents (invited review). Journal of Biomedicine and Biotechnology, 2(3): 124-130, 2002.

29. Raymond, J.A. and Plopper, G.E. A bacterial TMAO transporter. Comparative Biochemistry and Physiology, 133:29-34, 2002.

30. Wagner, J.E. , Huff, J.L., Rust W.L., Kingsley K., and Plopper, G.E. Perillyl alcohol inhibits breast cell migration without affecting cell adhesion. Journal of Biomedicine and Biotechnology, 2(3): 136-140, 2002.

31. Kingsley, K, K. Carroll, J.L. Huff, and G.E. Plopper. Photobleaching of arterial autofluorescence for immunofluorescence applications. BioTechniques, 30(4):794-797, 2001.

32. Buensuceso, C.S., D. Woodside, J.L.Huff, G.E. Plopper, and T.E. O’Toole. The WD protein Rack1 mediates PKC and integrin dependent cell migration. Journal of Cell Science, 114:1691-1698, 2001.

33. Rust, W.L., J.L. Huff, and G.E. Plopper. Screening assay for pro/anti-migratory compounds. Analytical Biochemistry, 280:11-19, 2000.

34. Plopper, G.E., J.L. Huff, W.L. Rust, M.A. Schwartz, and V. Quaranta. Antibody induced activation of

35. Rust, W., K. Kingsley, T. Petnicki, S. Padmanabhan, S.W. Carper, and G.E. Plopper. Hsp27 plays two distinct roles in controlling human breast cancer cell migration on laminin-5. Molecular Cell Biology Research Communications, 1:196-202, 1999.

36. Goldmann, W.H., J.L. Alonso, K. Bojanowski, C. Brangwynne, C.S. Chen, M.E. Chicurel, L. Dike, S. Huang, K.-M. Lee, A. Maniotis, R. Mannix, H. McNamee, C.J. Meyer, K. Naruse, K.K. Parker, G. Plopper, T. Polte, N. Wang, L. Yan, and D.E. Ingber. Cell shape control and mechanical signaling through the cytoskeleton. In: Carraway K, ed. The Cytoskeleton and Signaling: A Practical Approach. Oxford, England: Oxford University Press, pp. 245-276, 1999.

37. Plopper, G.E., Domanico, S., Kioses, B., and V. Quaranta. Laminin-5 induced adhesion and migration in mammary epithelial cells: Differential role of

38. Quaranta, V. and G.E. Plopper. Integrins and laminins in tissue remodeling. Kidney International 51(5):1441-1446, 1997.

39. Tamura, R.N., Oda, D., Quaranta, V., Plopper, G., Lambert, R., Glaser, S., and J.C.R. Jones. Coating of titanium alloy with soluble laminin-5R promotes cell attachment and hemidesmosome assembly in gingival epithelial cells: Potential application to dental implants. Journal of Periodontal Research 32:287-294, 1997.

40. Plopper, G., J. Falk-Marzillier, S. Glaser, M. Fitchmun, T. Romano, G. Gianelli, J.C.R. Jones, V. Quaranta. Changes in expression of monoclonal antibody epitopes on laminin-5r induced by cell contact. Journal of Cell Science 109: 1965-1973, 1996.

41. Baker, S.E., Hopkinson, S.B., Fitchmun, M., Andreason, G.L., Frasier, F., Plopper, G., Quaranta, V. and Jones, J.C.R. Laminin-5 and hemidesmosomes: role of the alpha3 chain subunit in hemidesmosome stability and assembly. Journal of Cell Science 109: 2509 - 2520, 1996.

42. Hormia, M., J. Falk-Marzillier, G. Plopper, R.N. Tamura, J.C.R. Jones, and V. Quaranta. Rapid spreading and mature hemidesmosome formation in HaCaT keratinocytes induced by incubation with soluble laminin-5r. Journal of Investigative Dermatology 105:557-561, 1995.

43. Plopper, G.E., H.P. McNamee, L.E. Dike, K. Bojanowski, D.E. Ingber. Integration of integrin and growth factor receptor signaling pathways within the focal adhesion complex. Molecular Biology of the Cell 6:1349-1365, 1995.

44. Kieffer, J.D., G. Plopper, D.E. Ingber, J.H. Hartwig, T.S. Kupper. Direct binding of F actin to the cytoplasmic domain of the beta1 integrin chain in vitro. Biochemical and Biophysical Research Communications 217:466-474, 1995.

45. Ingber, D.E. , L. Dike, L. Hansen, S. Karp, H. Liley, A. Maniotis, H. McNamee, D. Mooney, G. Plopper, J. Sims, and N. Wang. Cellular tensegrity: Expoloring how mechanical changes in the cytoskeleton regulate cell growth, migration, and tissue pattern during morphogenesis. International Reviws in Cytology 150:173-224, 1994.

46. Ingber, D., S. Karp, G. Plopper, L. Hansen, and D. Mooney. Mechanochemical transduction across extracellular matrix and through the cytoskeleton. In: Physical Forces and The Mammalian Cell (J. Francis and C.L. Ives, eds.). Academic Press: San Diego, 1993.

47. Plopper, G., and D.E. Ingber. Rapid induction and isolation of focal adhesion complexes. Biochemical and Biophysical Research Communications 193:571- 578, 1993.

48. Narula, N., I. McMorrow, G. Plopper, J. Doherty, K. Matlin, B. Burke, J. Stow. Identification of a 200-kD, brefeldin-sensitive protein on golgi membranes. Journal of Cell Biology 117:27-38, 1992.

49. McMorrow, I., W.E. Souter, G. Plopper, and B. Burke. Identification of a golgi-associated protein that undergoes mitosis dependent phosphorylation and relocation. Journal of Cell Biology 110:1513-24, 1990.

50. Renkin, E.M., W.L. Joyner, M. Gustafson-Sgro, G. Plopper, and L. Sibley. Albumin extravasation rates in tissues of anesthetized and unanesthetized rats. Journal of Applied Physiology 66:2056-60, 1989.