University of Minnesota
Department of Biomedical Engineering

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Chun Wang

Paolo Provenzano








Summary of Research

The microenvironment surrounding carcinoma cells influences cell behavior through complex interactions of biochemical factors, matrix architecture and matrix mechanical properties. Our research focuses on understanding the molecular mechanisms by which the stromal extracellular matrix and stromal cell populations influence epithelial cell behavior in cancer. We are particularly interested in how these factors influence disease progression and resistance to therapeutic intervention in breast and pancreas cancer. We utilize advanced quantitative imaging, cell and matrix mechanics, tissue engineered 3D microenvironments as well as cell and molecular biology techniques to gain a quantitative understanding of cancer cells behavior and develop novel technologies and therapeutic strategies for cancer diagnosis and treatment.

Focus Areas: Quantitative cancer biology, Cell-matrix interactions, Signal transduction, Mechanotransduction, Advanced optical imaging/Biophotonics

Selected Publications

Ray A, Lee O, Win Z, Edward RM, Alford PW, Kim DH, Provenzano PP Anisotropic forces from spatially constrained focal adhesions mediate contact guidance directed cell migration. Nature Communications 8:14923, 2017

Ray A, Slama ZM, Morford RK, Madden SA, Provenzano PP Enhanced Directional Migration of Cancer Stem Cells in 3D Aligned Collagen Matrices, Biophysical Journal, 112(5):1023-1036, 2017

Nam KH, Kim P, Wood D, Kwon S, Provenzano PP*, Kim DH*, Multiscale Cues Drive Collective Cell Migration, *Co-senior / corresponding authors Scientific Reports 6(29749), 2016

DuFort CC, DelGiorno KE, Carlson M, Osgood RJ, Zhao C, Huang Z, Shepard MH, Thompson CB, Conner RJ, Thanos CD, Brockenbrough S, Provenzano PP, Frost GI, Shepard MH, Hingorani SR Interstitial pressure in pancreatic ductal adenocarcinoma is dominated by a gel-fluid phase Biophysical Journal 110(9):2106-19, 2016

Provenzano PP, Cuevas C, Chang AE, Von Hoff DD, Hingorani, SR, Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma, Cancer Cell, 21(3), 418-429, 2012

Kim DH, Provenzano PP, Smith CL, Levchenko A, Understanding the role of nanotopographic cues in controlling cell functions, Journal of Cell Biology (review), 197(3), 351-60, 2012

Provenzano PP, Keely PJ, Mechanical signaling through the cytoskeleton regulates cell proliferation by coordinated focal adhesion and Rho GTPase singaling, Journal of Cell Science (review) 124(8), 1195-1205, 2011

Conklin MW, Eickhoff JC, Riching KM, Pehlke CA, Eliceiri KW, Provenzano PP, Friedl A, Keely PJ, Aligned collagen is a prognostic signature for survival in human breast carcinoma, American Journal of Pathology, 178(3): 1221-1232, 2011

Provenzano PP, Eliceiri KW, Keely PJ, Shining new light on 3D motility and the metastatic process, Trends in Cell Biology (review) 19(11): 638-648, 2009

Provenzano PP, Inman DR, Eliceiri KW, Keely PJ, Matrix density-induced stiffness regulates breast cell phenotype, signaling, and gene expression through a FAK-ERK linkage, Oncogene 28(49): 4326-4343, 2009

Rueden CT, Conklin MW, Provenzano PP, Keely PJ, Eliceiri KW, Nonlinear optical microscopy and computational analysis of intrinsic signatures in breast cancer, Proc IEEE Eng. Med. Biol. Soc. 4077-4090, 2009

Provenzano PP, Inman DR, Eliceiri KW, Keely PJ, Multiphoton microscopy and fluorescence lifetime imaging microscopy (FLIM) to monitor metastasis and the tumor microenvironment, Clinical & Experimental Metastasis – Special Issue: Imaging the Dynamics of Cancer (invited review) 26(4): 357-70, 2009

Conklin MW, Provenzano PP, Eliceiri KW, Sullivan R, Keely PJ, Fluorescence lifetime imaging of endogenous fluorophores in histopathology sections reveals differences between normal and tumor epithelium in carcinoma in situ of the breast, Cell Biochemistry and Biophysics, 53(3): 145-157, 2009

Provenzano PP, Inman DR, Trier SM, Eliceiri KW, Keely PJ, Contact guidance mediated 3D cell migration is regulated by Rho/ROCK-dependent matrix reorganization, Biophysical Journal, 95: 5374-5384, 2008

Provenzano PP, Inman DR, Eliceiri KW, Beggs HE, Keely PJ, Mammary epithelial-specific disruption of focal adhesion kinase retards tumor formation and metastasis in a transgenic mouse model of human breast cancer, American Journal of Pathology, 173(5): 1551-1565, 2008

Provenzano PP, Rueden CT, Trier SM, Yan L, Ponik SM, Inman DR, Keely PJ, and Eliceiri KW, Nonlinear optical imaging and spectral-lifetime computational analysis of endogenous and exogenous fluorophores in breast cancer, Journal of Biomedical Optics, 13(3): 031220, 2008

Provenzano PP, Eliceiri KW, Campbell JW, Inman DR, White JG, Keely PJ, Collagen reorganization at the tumor-stromal interface facilitates local invasion, BMC Medicine 34(1): 2006