Center for Matrix Biology - Vanderbilt University and Medical Center

Vito Quaranta, M.D.
Professor in the Department of Cancer Biology
Co-Director, Vanderbilt Center for Matrix Biology

	Office Address:	771 PRB
	Mailing Address:	2220 Pierce Avenue 771 PRB Nashville, TN 37232
	Lab address:	446B PRB
	Phone:	(615) 936-2868
		email \| website

Research Summary

CANCER SYSTEMS BIOLOGY

Cancer Systems Biology is the definition of our mixed experimental and theoretical approach to studying many aspects of cancer progression, including invasion, metastasis, resistance to drugs, effects of mutations. Rather than focusing on clarifying details of a molecular or genetic pathway, or specific effects of growth or differentiation factors or proteases or drugs, we try and combine these details into a global picture that specifies overall trends in growth and progression of specific cancer cells under distinct microenvironmental conditions. Thus, we build quantitative hypotheses that translate experimental observations or datasets into computer simulations based of several mathematical modeling techniques, including ordinary or partial differential equations, cellular automata, neural networks, immersed boundary method. To test the hypotheses, we populate these models with datasets from in vitro or animal experiments, or from clinical material. The simulations make theoretical predictions on specific ways experimental variables may affect cancer progression. We then design and perform experiments to validate these predictions, and the outcome of the experimentation is used to evaluate the realism of computer simulations and possibly modify their underlying mathematics. Our group is comprised of an interdisciplinary collection of scientists, including cell and molecular biologists, mathematicians, engineers, bioengineers, bioinformaticians and computational biologists. We thrive on continued personal exchange and looking at cancer research problems through the eyes of different disciplines.

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Associated initiative(s):

Angiogenesis

Biomaterials

Tissue Regeneration

Tumor Microenvironment

Wound Repair

Career opportunities:
Postdoctoral Position Available

Selected Publications

» Hinow, P, Gerlee, P, McCawley, LJ, Quaranta, V, Ciobanu, M, Wang, S, Graham, JM, Ayati, BP, Claridge, J, Swanson, KR, Loveless, M, Anderson, AR A spatial model of tumor-host interaction: Application of chemotherapy Math Biosci Eng 2009. 6:521-46

» Guess, CM, Lafleur, BJ, Weidow, BL, Quaranta, V A decreased ratio of laminin-332 beta3 to gamma2 subunit mRNA is associated with poor prognosis in colon cancer Cancer Epidemiol Biomarkers Prev 2009. 18:1584-90

» Kam, Y, Quaranta, V Cadherin-bound beta-catenin feeds into the Wnt pathway upon adherens junctions dissociation: evidence for an intersection between beta-catenin pools PLoS One 2009. 4:e4580

» Wang, SE, Xiang, B, Zent, R, Quaranta, V, Pozzi, A, Arteaga, CL Transforming growth factor beta induces clustering of HER2 and integrins by activating Src-focal adhesion kinase and receptor association to the cytoskeleton Cancer Res 2009. 69:475-82

» Anderson, AR, Rejniak, KA, Gerlee, P, Quaranta, V Microenvironment driven invasion: a multiscale multimodel investigation J Math Biol 2009. 58:579-624

» Kam, Y, Guess, C, Estrada, L, Weidow, B, Quaranta, V A novel circular invasion assay mimics in vivo invasive behavior of cancer cell lines and distinguishes single-cell motility in vitro BMC Cancer 2008. 8:198

» Quaranta, V, Rejniak, KA, Gerlee, P, Anderson, AR Invasion emerges from cancer cell adaptation to competitive microenvironments: quantitative predictions from multiscale mathematical models Semin Cancer Biol 2008. 18:338-48

» Georgescu, W, Jourquin, J, Estrada, L, Anderson, AR, Quaranta, V, Wikswo, JP Model-controlled hydrodynamic focusing to generate multiple overlapping gradients of surface-immobilized proteins in microfluidic devices Lab Chip 2008. 8:238-44

» Harris, MP, Kim, E, Weidow, B, Wikswo, JP, Quaranta, V Migration of isogenic cell lines quantified by dynamic multivariate analysis of single-cell motility Cell Adh Migr 2008. 2:127-36

» Tripathi, M, Nandana, S, Yamashita, H, Ganesan, R, Kirchhofer, D, Quaranta, V Laminin-332 is a substrate for hepsin, a protease associated with prostate cancer progression J Biol Chem 2008. 283:30576-84

» Anderson, AR, Quaranta, V Integrative mathematical oncology Nat Rev Cancer 2008. 8:227-34

» Hu, G, Quaranta, V, Li, D Modeling of effects of nutrient gradients on cell proliferation in microfluidic bioreactor Biotechnol Prog 2007. 23:1347-54

» Jourquin, J, Yang, N, Kam, Y, Guess, C, Quaranta, V Dispersal of epithelial cancer cell colonies by lysophosphatidic acid (LPA) J Cell Physiol 2006. 206:337-46

» Anderson, AR, Weaver, AM, Cummings, PT, Quaranta, V Tumor morphology and phenotypic evolution driven by selective pressure from the microenvironment Cell 2006. 127:905-15

» Quaranta, V, Weaver, AM, Cummings, PT, Anderson, AR Mathematical modeling of cancer: the future of prognosis and treatment Clin Chim Acta 2005. 357:173-9

» Hintermann, E, Yang, N, O''Sullivan, D, Higgins, JM, Quaranta, V Integrin alpha6beta4-erbB2 complex inhibits haptotaxis by up-regulating E-cadherin cell-cell junctions in keratinocytes J Biol Chem 2005. 280:8004-15

» Wang, H., Fu, W., Im, J.H., Zhou, Z., Santoro, S.A., Iyer, V., Dipersio, C.M., Yu, Q.C., Quaranta, V. Tumor cell alpha3beta 1 integrin and vascular laminin-5 mediate pulmonary arrest and metastasis. J Cell Biol 2004. 164:935-941

» Hintermann, E, Quaranta, V Epithelial cell motility on laminin-5: regulation by matrix assembly, proteolysis, integrins and erbB receptors Matrix Biol 2004. 23:75-85

» Bilban, M, Ghaffari-Tabrizi, N, Hintermann, E, Bauer, S, Molzer, S, Zoratti, C, Malli, R, Sharabi, A, Hiden, U, Graier, W, Kn??fler, M, Andreae, F, Wagner, O, Quaranta, V, Desoye, G Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts J Cell Sci 2004. 117:1319-28

» Schenk, S., Quaranta, V. Tales from the crypt [ic] sites of the extracellular matrix Trends Cell Biol 2003. 13:366-375

» Quaranta, V., Giannelli, G. Cancer invasion:watch your neighbourhood Tumori 2003. 89:343-348

» Gao, Changshou, Mao, Shenlan, Ronca, Francesca, Zhuang, Sufei, Quaranta, Vito, Wirsching, Peter, Janda, Kim D, De novo identification of tumor-specific internalizing human antibody-receptor pairs by phage-display methods. J Immunol Methods 2003. 274:185-97

» Piril??, Emma, Sharabi, Andrew, Salo, Tuula, Quaranta, Vito, Tu, Hongmin, Heljasvaara, Ritva, Koshikawa, Naohiko, Sorsa, Timo, Maisi, P??ivi, Matrix metalloproteinases process the laminin-5 gamma 2-chain and regulate epithelial cell migration. Biochem Biophys Res Commun 2003. 303:1012-7

» Schenk, Susann, Hintermann, Edith, Bilban, Martin, Koshikawa, Naohiko, Hojilla, Carlo, Khokha, Rama, Quaranta, Vito, Binding to EGF receptor of a laminin-5 EGF-like fragment liberated during MMP-dependent mammary gland involution. J Cell Biol 2003. 161:197-209

» Schenk, Susann, Quaranta, Vito, Tales from the crypt[ic] sites of the extracellular matrix. Trends Cell Biol 2003. 13:366-75

» Hendrix, Mary J C, Seftor, Elisabeth A, Kirschmann, Dawn A, Quaranta, Vito, Seftor, Richard E B, Remodeling of the microenvironment by aggressive melanoma tumor cells. Ann N Y Acad Sci 2003. 995:151-61

» Quaranta, V Motility cues in the tumor microenvironment Differentiation 2002. 70:590-8

» Hintermann, E, Haake, SK, Christen, U, Sharabi, A, Quaranta, V Discrete proteolysis of focal contact and adherens junction components in Porphyromonas gingivalis-infected oral keratinocytes: a strategy for cell adhesion and migration disabling Infect Immun 2002. 70:5846-56

» Quaranta, V Motility cues in the tumor microenvironment Differentiation 2002. :590-598

» Giannelli, G., Bergamini, C., Fransvea, E., Marinosci, F., Quaranta, V., and Antonaci, S. Human hepatocellular carcinoma (HCC) cells require both alpha3beta1 integrin and matrix metalloproteinases activity for migration and invasion. Lab Invest 2001. 81:613-627

» Hintermann, E., Bilban, M., Sharabi, A., and Quaranta, V. Inhibitory role of alpha6beta 4-associated erbB-2 and phosphoinositide 3-kinase in keratinocyte haptotactic migration dependent on alpha3beta1 integrin J Cell Biol 2001. 153:465-475

» Seftor, R.E., Seftor, E.A., Koshikawa, N., Meltzer, P.S., Gardner, L.M., Bilban, M., Stetler-Stevenson, W.G., Quaranta, V., and Hendrix, M.J. Cooperative interactions of laminin 5 gamma2 chain, matrix metalloproteinase-2, and membrane type-1-matrix/metalloproteinase are required for mimicry of embryonic vasculogenesis by aggressive melanoma. Cancer Res 2001. 61:6322-6327

» Shang, M., Koshikawa, N., Schenk, S., and Quaranta, V. The LG3 module of laminin-5 harbors a binding site for integrin alpha3beta1 that promotes cell adhesion, spreading, and migration J Biol Chem 2001. 276:33045-33053

» Hintermann, E, Bilban, M, Sharabi, A, Quaranta, V Inhibitory role of alpha 6 beta 4-associated erbB-2 and phosphoinositide 3-kinase in keratinocyte haptotactic migration dependent on alpha 3 beta 1 integrin J Cell Biol 2001. 153:465-78

» Kiosses, W.B., Hahn, K.M., Giannelli, G., and Quaranta, V. Characterization of morphological and cytoskeletal changes in MCF10A breast epithelial cells plated on laminin-5: comparison with breast cancer cell line MCF7. Cell Adhes Commun 2001. 8:29-44

» Zent, R., Bush, K.T., Pohl, M.L., Quaranta, V., Koshikawa, N., Wang, Z., Kreidberg, J.A., Sakurai, H., Stuart, R.O., and Nigam, S.K. Involvement of laminin binding integrins and laminin-5 in branching morphogenesis of the ureteric bud during kidney development. Dev Biol 2001. 238:289-302

» Plopper,G.E., Huff, J.L., Rust, W.L., Schwartz, M.A.,Quaranta, V. Antibody-induced activation of betal integrin receptors stimulates cAMP-dependent migration of breast cells on laminin-5 Mol. Cell Biol Res Commun 2000. 4:129-135

» Quaranta, V. Cell migration through extracellular matrix; membrane-type metalloproteinases make the way. J Cell Biol 2000. :1167-1179

» Mullen, L.M., Richards, D.W., Quaranta, V. Evidence that laminin-5 is a component of the tooth surface internal basal lamina, supporting epithelial cell adhesion J. Periodontal Res 1999. 34:16-24

» Falk-Marzillier, J., Domanico, S.Z., Pelletier, A, Mullen, L., Quaranta, V. Characterization of a tight molecular complex between integrin alpha6beta4 and laminin-5 extracellular matrix Biochem Biophys Res Commun 1998. 251:49-55

» Quaranta, V., Plopper, G.E. Integrins and laminins in tissue remodeling Kidney Int. 1997. 51:1441-1446

» Giannelli, G., Falk-Marzillier, J., Schiraldi, O., Stetler-Stevenson, W.G., Quaranta, V. Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5 Science 1997. 277:225-228

» Baker, S.E., DiPasquale, A.P., Stock, E.L., Quaranta, V., Fitchmum, M., Jones, J.C. Morphogenetic effects of soluble laminin-5 on cultured epithelial cells and tissue explants. Exp. Cell Res. 1996. 228:262-270

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

» Plopper, G., Falker-Marzillier, J., Glaser, S., Fitchmum, M., Giannelli, G., Romano, T., Jones, J.C., Quaranta, V. Changes in expression of monoclonal antibody epitopes on laminin-5r induced by cell contact J Cell Sci 1996. :

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

» Hormia, M., Falk-Marzillier, J., Plopper, G. Tamura, R.N., Jones, J.C., Quaranta, V. Rapid spreading and mature hemidesmosome formation in HaCaT Keratinocytes induced by incubation with soluble laminin-5r J Invest Dermatol 1995. :557-561

» Quaranta, V., Collo, G., Rozzo, C., Starr, L., Gaietta, G., Tamura, R.N. The integrin alpha6beta4 in epithelial and carcinoma cells. The Integrins 1994. :147-176

» Gaietta, G., Redelmeier, T.E., Jackson, M.R., Tamura, R.N. Quaranta, V. Quantitative measurment of alpha6beta 1 and alpha6beta 4 integrin internalization under cross-linking conditions: a possible role for alpha6 cytoplasmic domains J Cell Sci 1994. 107:3339-3349

» Quaranta, V.,Tamura, R.N. Collo, G., Cooper, H.M., Hormia, M., Rozzo, C. Gaietta, G., Starr, L. Distinctive functions of alpha6beta4 and other integrins in epithelial cells. Intergrins 1994. :141-161

» Collo, G., Starr, L., Quaranta, V. A new isoform of the laminin receptor integrin alpha 7 beta 1 is developmentally regulated in skeletal muscle. J. Biol. Chem 1993. 268:19019-19024

» Quaranta, V. Integrin expression and epithelial cell differentiation. I Cell Adhesion Molecules 1993. :13-27

» Hormia, M., Virtanen, I., Quaranta, V. Immunolocalization of intergrin alpha 6 beta 4 in mouse junctional epithelium suggests an anchoring function to both the internal and the external basal lamina. J Dent Res 1992. 71:1503-1508

» Quaranta, V., Jones, J.C. The internal affairs of an integrin. Trends in Cell Biology 1991. 1:2-4

» Tamura, R.N., Cooper, H.M., Collo, G., Quaranta, V. Cell type-specific integrin variants with alternative alpha chain cytoplasmic domains Proc Natl. Acad. Sci US 1991. A 88:10183-10187