Vito Quaranta, M.D.
Professor of Cancer Biology
771 Preston Building
2220 Pierce Avenue
Nashville, TN 37232
Dr. Vito Quaranta is a Professor of Cancer Biology, Director of the Integrative Cancer Biology Center and Co-Director of the Center for Matrix Biology at Vanderbilt University Medical School, Nashville, TN. His fields of interest are oncology and matrix biology.
Cancer Systems Biology; Cell Adhesion and Migration
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.
My background is in cancer cell biology, and since 2004 I have gradually transitioned my interests to Cancer Systems Biology. Before my systems biology time, my main interest was discovery of molecular mechanisms whereby integrins and extracellular matrix, especially laminins, modify the microenvironment of cancer cells and affect their behavior. My laboratory has made several contributions on integrin structure/function, and on cancer cell motility onto matrix digested by proteases. These cancer microenvironment studies motivated me to seek approaches that evaluate simultaneously the many variables affecting cancer cell functional phenotypes. Computer and mathematical modeling was an obvious avenue to pursue, and I have been fortunate to encounter brilliant mathematicians with whom I have established productive and exciting collaborations. Through these, I entertain connections with a large world-wide community of systems biologists and mathematical modelers. Our Center for Cancer Systems Biology at Vanderbilt is part of an NCI-funded Integrative Cancer Biology Program that links 12 Centers nationwide with biannual meetings. My group has diversified to include an interdisciplinary collection of cell and molecular biologists, mathematicians, engineers, bioengineers, bioinformaticians and computational biologists. In my group we specialize in connecting cell functional phenotypes with underlying molecular networks, using cell-based modeling techniques resulting in models that can accept large cellular datasets. Vice versa, we insist on establishing in advance that simulation outputs and predictions of computer models we build and study can in fact be validated experimentally. We also investigate noise and robustness in signaling, as it may become modified in cancer progression or in response to stress, drugs (e.g., molecular therapeutics) and microenvironmental perturbations. The goal of our systems approach is to build fundamental knowledge of cancer as a complex process, and seek short-term translational applications of this knowledge. The latter goal is most relevant to rational deployment of targeted therapeutics, one of the most exciting development for cancer treatment in decades. With respect to this goal, my group interacts productively with oncologists (both clinical and surgica
- Xu, J, Xie, J, Jourquin, J, Colvin, DC, Does, MD, Quaranta, V, Gore, JC Influence of cell cycle phase on apparent diffusion coefficient in synchronized cells detected using temporal diffusion spectroscopy. Magn Reson Med, 65(4), 920-6, 2011.
- Tripathi, M, Potdar, AA, Yamashita, H, Weidow, B, Cummings, PT, Kirchhofer, D, Quaranta, V Laminin-332 cleavage by matriptase alters motility parameters of prostate cancer cells. Prostate, 71(2), 184-96, 2011.
- Jeon, J, Quaranta, V, Cummings, PT An off-lattice hybrid discrete-continuum model of tumor growth and invasion. Biophys J, 98(1), 37-47, 2010.
- Gruver, JS, Potdar, AA, Jeon, J, Sai, J, Anderson, B, Webb, D, Richmond, A, Quaranta, V, Cummings, PT, Chung, CY Bimodal analysis reveals a general scaling law governing nondirected and chemotactic cell motility. Biophys J, 99(2), 367-76, 2010.
- Ocak, S, Yamashita, H, Udyavar, AR, Miller, AN, Gonzalez, AL, Zou, Y, Jiang, A, Yi, Y, Shyr, Y, Estrada, L, Quaranta, V, Massion, PP DNA copy number aberrations in small-cell lung cancer reveal activation of the focal adhesion pathway. Oncogene, 29(48), 6331-42, 2010.
- Hassanein, M, Weidow, B, Koehler, E, Bakane, N, Garbett, S, Shyr, Y, Quaranta, V Development of High-Throughput Quantitative Assays for Glucose Uptake in Cancer Cell Lines. Mol Imaging Biol, 2010.
- Yamashita, H, Shang, M, Tripathi, M, Jourquin, J, Georgescu, W, Liu, S, Weidow, B, Quaranta, V Epitope mapping of function-blocking monoclonal antibody CM6 suggests a "weak" integrin binding site on the laminin-332 LG2 domain. J Cell Physiol, 223(3), 541-8, 2010.
- Potdar, AA, Jeon, J, Weaver, AM, Quaranta, V, Cummings, PT Human mammary epithelial cells exhibit a bimodal correlated random walk pattern. PLoS One, 5(3), e9636, 2010.
- Liu, S, Yamashita, H, Weidow, B, Weaver, AM, Quaranta, V Laminin-332-beta1 integrin interactions negatively regulate invadopodia. J Cell Physiol, 223(1), 134-42, 2010.
- Yamashita, H, Tripathi, M, Jourquin, J, Kam, Y, Liu, S, Weidow, B, Quaranta, V Lysophosphatidic Acid Upregulates Laminin-332 Expression during A431 Cell Colony Dispersal. J Oncol, 20102010.
- Riggins, KS, Mernaugh, G, Su, Y, Quaranta, V, Koshikawa, N, Seiki, M, Pozzi, A, Zent, R MT1-MMP-mediated basement membrane remodeling modulates renal development. Exp Cell Res, 316(17), 2993-3005, 2010.
- Quaranta, V, Garbett, SP Not all noise is waste. Nat Methods, 7(4), 269-72, 2010.
- Yamashita, H, Tripathi, M, Harris, MP, Liu, S, Weidow, B, Zent, R, Quaranta, V The role of a recombinant fragment of laminin-332 in integrin alpha3beta1-dependent cell binding, spreading and migration. Biomaterials, 31(19), 5110-21, 2010.
- 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, 18(5), 1584-90, 2009.
- 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, 6(3), 521-46, 2009.
- 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, 4(2), e4580, 2009.
- Guess, CM, Quaranta, V Defining the role of laminin-332 in carcinoma. Matrix Biol, 28(8), 445-55, 2009.
- Anderson, AR, Rejniak, KA, Gerlee, P, Quaranta, V Microenvironment driven invasion: a multiscale multimodel investigation. J Math Biol, 58(4-5), 579-624, 2009.
- Quaranta, V, Tyson, DR, Garbett, SP, Weidow, B, Harris, MP, Georgescu, W Trait variability of cancer cells quantified by high-content automated microscopy of single cells. Methods Enzymol, 46723-57, 2009.
- 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, 69(2), 475-82, 2009.
- 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, 8198, 2008.
- Anderson, AR, Quaranta, V Integrative mathematical oncology. Nat Rev Cancer, 8(3), 227-34, 2008.
- 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, 18(5), 338-48, 2008.
- 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, 283(45), 30576-84, 2008.
- 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, 2(2), 127-36, 2008.
- 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, 8(2), 238-44, 2008.
- Hu, G, Quaranta, V, Li, D Modeling of effects of nutrient gradients on cell proliferation in microfluidic bioreactor. Biotechnol Prog, 23(6), 1347-54, 2007.
- Jourquin, J, Yang, N, Kam, Y, Guess, C, Quaranta, V Dispersal of epithelial cancer cell colonies by lysophosphatidic acid (LPA). J Cell Physiol, 206(2), 337-46, 2006.
- Anderson, AR, Weaver, AM, Cummings, PT, Quaranta, V Tumor morphology and phenotypic evolution driven by selective pressure from the microenvironment. Cell, 127(5), 905-15, 2006.
- 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, 280(9), 8004-15, 2005.
- Quaranta, V, Weaver, AM, Cummings, PT, Anderson, AR Mathematical modeling of cancer: the future of prognosis and treatment. Clin Chim Acta, 357(2), 173-9, 2005.
- Hintermann, E, Quaranta, V Epithelial cell motility on laminin-5: regulation by matrix assembly, proteolysis, integrins and erbB receptors. Matrix Biol, 23(2), 75-85, 2004.
- Bilban, M, Ghaffari-Tabrizi, N, Hintermann, E, Bauer, S, Molzer, S, Zoratti, C, Malli, R, Sharabi, A, Hiden, U, Graier, W, KnÃ¶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, 117(Pt 8), 1319-28, 2004.
- 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, 164935-941, 2004.
- 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, 161197-209, 2003.
- Quaranta, V., Giannelli, G. "Cancer invasion:watch your neighbourhood." Tumori, 89343-348, 2003.
- 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, 274185-97, 2003.
- PirilÃ¤, Emma, Sharabi, Andrew, Salo, Tuula, Quaranta, Vito, Tu, Hongmin, Heljasvaara, Ritva, Koshikawa, Naohiko, Sorsa, Timo, Maisi, PÃ¤ivi, Matrix metalloproteinases process the laminin-5 gamma 2-chain and regulate epithelial cell migration.. Biochem Biophys Res Commun, 3031012-7, 2003.
- 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, 995151-61, 2003.
- Schenk, S., Quaranta, V. "Tales from the crypt [ic] sites of the extracellular matrix." Trends Cell Biol, 13366-375, 2003.
- Schenk, Susann, Quaranta, Vito, Tales from the crypt[ic] sites of the extracellular matrix.. Trends Cell Biol, 13366-75, 2003.
- 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, 70(10), 5846-56, 2002.
- Quaranta, V Motility cues in the tumor microenvironment. Differentiation, 70(9-10), 590-8, 2002.
- Quaranta, V "Motility cues in the tumor microenvironment." Differentiation, 590-598, 2002.
- 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, 829-44, 2001.
- 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, 616322-6327, 2001.
- 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, 81613-627, 2001.
- 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, 153(3), 465-78, 2001.
- 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, 153465-475, 2001.
- 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, 238289-302, 2001.
- 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, 27633045-33053, 2001.
- 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 , 4129-135, 2000.
- Quaranta, V. "Cell migration through extracellular matrix; membrane-type metalloproteinases make the way.." J Cell Biol, (149), 1167-1179, 2000.
- 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, 3416-24, 1999.
- 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, 25149-55, 1998.
- 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, 277225-228, 1997.
- Quaranta, V., Plopper, G.E. "Integrins and laminins in tissue remodeling." Kidney Int., 511441-1446, 1997.
- 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 , 2509-2520, 1996.
- 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 , 1092509-2520, 1996.
- 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. , 228262-270, 1996.
- 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, 557-561, 1995.
- 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, 141-161, 1994.
- 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 , 1073339-3349 , 1994.
- Quaranta, V., Collo, G., Rozzo, C., Starr, L., Gaietta, G., Tamura, R.N. "The integrin alpha6beta4 in epithelial and carcinoma cells.." The Integrins, 147-176, 1994.
- 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, 26819019-19024, 1993.
- Quaranta, V. "Integrin expression and epithelial cell differentiation. I." Cell Adhesion Molecules, 13-27, 1993.
- 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, 711503-1508, 1992.
- 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 , A 8810183-10187, 1991.
- Quaranta, V., Jones, J.C. "The internal affairs of an integrin.." Trends in Cell Biology, 12-4, 1991.