The Chen Lab

A 3D biomimetic model of lymphatics reveals cell-cell junction tightening and lymphedema via a cytokine-indced ROCK2/JAM-A complex. 

Lee, E., Chan, S.L., Lee, Y., Polacheck, W.J., Kwak, S., Wen, A., Nguyen, D.H.T., Kutys, M.L., Alimperti, S., Kolarzyk, A.M., Kwak, T.J., Eyckmans, J., Bielenberg, D.R., Chen, H., Chen, C.S. (2023) Proc Natl Acad Sci USA. 120(41):e2308941120. doi: 10.1073/pnas.2308941120.  PMCID: PMC10576061

Next-generation engineered microsystems for cell biology: a systems-level roadmap.

Sundaram S, Chen CS. Trends Cell Biol. 2022 Jun;32(6):490-500.

Notch1 and Notch3 coordinate for pericyte-induced stabilization of vasculature.

Am J Physiol Cell Physiol. Tefft JB, Bays JL, Lammers A, Kim S, Eyckmans J, Chen CS.2022 Feb 1;322(2):C185-C196.

Plakophilin-2 truncating variants impair cardiac contractility by disrupting sarcomere stability and organization.

Zhang K, Cloonan PE, Sundaram S, Liu F, Das SL, Ewoldt JK, Bays JL, Tomp S, Toepfer CN, Marsiglia JDC, Gorham J, Reichart D, Eyckmans J, Seidman JG, Seidman CE, Chen CS. Sci Adv. 2021 Oct 15;7(42):eabh3995.

Filamin C Cardiomyopathy Variants Cause Protein and Lysosome Accumulation.

Agarwal R, Paulo JA, Toepfer CN, Ewoldt JK, Sundaram S, Chopra A, Zhang Q, Gorham J, DePalma SR, Chen CS, Gygi SP, Seidman CE, Seidman JG. Circ Res. 2021 Sep 17;129(7):751-766.

SARS-CoV-2 Disrupts Proximal Elements in the JAK-STAT Pathway.

Chen DY, Khan N, Close BJ, Goel RK, Blum B, Tavares AH, Kenney D, Conway HL, Ewoldt JK, Chitalia VC, Crossland NA, Chen CS, Kotton DN, Baker SC, Fuchs SY, Connor JH, Douam F, Emili A, Saeed M. J Virol. 2021 Sep 9;95(19):e0086221.

Force-FAK signaling coupling at individual focal adhesions coordinates mechanosensing and microtissue repair.

Zhou DW, Fernández-Yagüe MA, Holland EN, García AF, Castro NS, O'Neill EB, Eyckmans J, Chen CS, Fu J, Schlaepfer DD, García AJ. Nat Commun. 2021 Apr 21;12(1):2359.

Probing the subcellular nanostructure of engineered human cardiomyocytes in 3D tissue.

Javor J, Ewoldt JK, Cloonan PE, Chopra A, Luu RJ, Freychet G, Zhernenkov M, Ludwig K, Seidman JG, Seidman CE, Chen CS, Bishop DJ. Microsyst Nanoeng. 2021 Jan 27;7:10.

Responses to acute infection with SARS-CoV-2 in the lungs of rhesus macaques, baboons and marmosets.

Singh DK, Singh B, Ganatra SR, Gazi M, Cole J, Thippeshappa R, Alfson KJ, Clemmons E, Gonzalez O, Escobedo R, Lee TH, Chatterjee A, Goez-Gazi Y, Sharan R, Gough M, Alvarez C, Blakley A, Ferdin J, Bartley C, Staples H, Parodi L, Callery J, Mannino A, Klaffke B, Escareno P, Platt RN 2nd, Hodara V, Scordo J, Gautam S, Vilanova AG, Olmo-Fontanez A, Schami A, Oyejide A, Ajithdoss DK, Copin R, Baum A, Kyratsous C, Alvarez X, Ahmed M, Rosa B, Goodroe A, Dutton J, Hall-Ursone S, Frost PA, Voges AK, Ross CN, Sayers K, Chen C, Hallam C, Khader SA, Mitreva M, Anderson TJC, Martinez-Sobrido L, Patterson JL, Turner J, Torrelles JB, Dick EJ Jr, Brasky K, Schlesinger LS, Giavedoni LD, Carrion R Jr, Kaushal D. Nat Microbiol. 2021 Jan;6(1):73-86.

Optogenetic current in myofibroblasts acutely alters electrophysiology and conduction of co-cultured cardiomyocytes. 

GM Kostecki, Y Shi, CS Chen, DH Reich, E Entcheva, L Tung. Scientific Reports 11 (1), 1-12

Harnessing Mechanobiology for Tissue Engineering.

Kim, S. Uroz, M. Bays, J.L., Chen, C.S. (2021).  Dev. Cell. doi: 10.1016/j.devcel.2020.12.017. PMCID: PMC7855812.

Reconstituting the dynamics of endothelial cells and fibroblasts in wound closure. 

Tefft, J. Eyckmans, J., Chen, C.S. (2021). APL Bioeng. doi: 10.1063/5.0028651. PMCID: PMC7817247.

Extracellular Matrix Alignment Directs Provisional Matrix Assembly and 3D Fibrous Tissue Closure. 

Das, S.L., Bose, P., Lejeune, E., Reich, D., Chen, C.S., Eyckmans, J. (2021). Tissue Engineering. doi: 10.1089/ten.TEA.2020.0332.

Controlled Cell Alignment Using Two-Photon Direct Laser Writing-Patterned Hydrogels in 2D and 3D. 

Song, J., Michas, C., Chen, C.S., White, A.E., Grinstaff, M.W. (2021). Macromolecular Bioscience. doi: 10.1002/mabi.202100051. PMID:33738917.

Direct Laser Writing for Cardiac Tissue Engineering: a Microfluidic Heart on a Chip with Integrated Transducers. 

Jayne, R.K., Karakan, M.C., Zhang, K., Pierce, N., Michas, C., Bishop, D.J., Chen, C.S., Ekinci, K.L., White, A.E. (2021) Lab on a Chip. doi: 10.1039/D0LC01078B.

Probing the subcellular nanostructure of engineered human cardiomyocytes in 3D tissue. 

Javor, J., Ewoldt, J.K., Cloonan, P.E., Chopra, A., Luu, R. J., Freychet, G., Zhernenkov, M., Ludwig, K., Seidman, J.G., Seidman, C. E., Chen, C.S., Bishop, D.J. (2021). Microsystems and Nanoengineering. 7:10. doi: 10.1038/s41378-020-00234-x

Mechanisms of Congenital Heart Disease Caused by NAA15 Haploinsufficiency

Ward, T., Warren, T.,  Morton, S., Impens, F., Van Damme, P., Van Haver, D., Timmerman, E., Venturini, G., Zhang, K., Jang, M.Y., Willcox, J. A. L., Haghighi, A., Gelb, B.G., Chung, W.K., Goldmuntz, E., Porter Jr., G. A., Lifton, R. P., Brueckner, M., Yost, H. J.,  Bruneau, B. G., Gorham, J., Kim, Y., Pereira, A., Homsy, J., Benson, C. C., DePalma S.R., Varland, S., Chen, C.S., Arnesen, T. (2021) doi: 10.1161/CIRCRESAHA.120.316966.

Recovery of Tractions Exerted by Single Cells in Three-Dimensional Nonlinear Matrices.

Song, D., Dong, L., Gupta, M., Li, L., Klaas, O., Loghin, A., Beall, M., Chen, C. S., Oberai, A. A. (2020). ASME. J Biomech Eng. 142(8): 081012. doi:10.1115/1.4046974

Uncovering Mutation-specific Morphogenic Phenotypes and Paracrine-mediated Vessel Dysfunction in a Biomimetic Vascularized Mammary Duct Platform. 

Kutys M.L., Polacheck, W.J., Welch M.K., Gagnon K.A., Koorman T., Kim S., Li L., McClatchey A.I., Chen C.S. (2020) Nature Comm. 11 (1): 1-11.

Transient Support from Fibroblasts is Sufficient to Drive Functional Vascularization in Engineered Tissues.

Song H.H., Lammers A., Sundaram S., Rubio R., Chen A.X., Li L., Eyckmans J., Bhatia S.N., Chen C.S. (2020) Adv. Funct. Mater. 2020; 2003777. doi:10.1002/adfm.202003777

Mechanical Regulation of Glycolysis via Cytoskeleton Architecture.

Park J.S., Burckhardt C.J., Lazcano R., Solis L.M., Isogai T., Li L., Chen C.S., Gao B., Minna J.D., Bachoo R., DeBerardinis R.J., Danuser G. (2020) Nature (London). 578 (7796): 621-26. PMID: 32051585

Myosin Sequestration Regulates Sarcomere Function, Cardiomyocyte Energetics, and Metabolism, Informing the Pathogenesis of Hypertrophic Cardiomyopathy. 

Toepfer C.N., Garfinkel A.C., Venturini G.,Wakimoto, H., Repetti, G., Alamo, L., Sharma,A., Agarwal, R., Ewoldt, J.F., Cloonan, P., Letendre, J., Lun, M., Olivotto, I., Colan, S., Ashley, E., Jacoby, D., Michels, M., Redwood,C.S., Watkins, H.C., Day, S.M., Staples, J.F., Padrón, R., Chopra, A., Ho, C.Y., Chen, C.S., Pereira, A.C., Seidman, J.G., Seidman, C.E. Circulation. 2020;141(10):828-842. PMID: 32150472

Controlled Apoptosis of Stromal Cells to Engineer Human Microlivers.

Chen, A. X., Chhabra, A., Song, H.‐H. G., Fleming, H. E., Chen, C. S., Bhatia, S. N. Adv. Funct. Mater. 2020, 1910442.

From Simple to Architecturally Complex Hydrogel Scaffolds for Cell and Tissue Engineering Applications: Opportunities Presented by Two-Photon Polymerization.

Song, J., Michas, C., Chen, C. S., White, A. E., & Grinstaff, M. W. (2020). Adv Healthc Mater, 9(1), e1901217.3 PMID: 31746140

Voltage Imaging of Cardiac Cells and Tissue Using the Genetically Encoded Voltage Sensor Archon1.

Shroff, S. N., Das, S. L., Tseng, H. -A., Noueihed, J., Fernandez, F., White, J. A., Chen, C.S., Han, X. (2020). iScience, 23(4), 100974. PMCID: PMC7160579

SarcTrack An Adaptable Software Tool for Efficient Large-Scale Analysis of Sarcomere Function in hiPSC-Cardiomyocytes. 

Toepfer, C.N., Sharma, A., Cicconet, M., Garfinkel, A.C., Mücke, M., Neyazi, M., Wilcox, J.A. L., Agarwal, R., Schmid, M., Rao, J., Ewoldt, J., Pourquié, O., Chopra, A., Chen, C.S., Seidman, J.G., Seidman, C.E (2019)., Circulation Research. 124:1172-1183. doi:10.1161/CIRCRESAHA.118.314505. PMCID: PMC6485312

A Biomimetic Pancreatic Cancer On-Chip Reveals Endothelial Ablation via ALK7 Signaling. 

Nguyen D.T., Lee E., Alimperti S., Norgard R.J., Wong A., Lee J.J., Eyckmans J., Stanger B.Z., Chen C.S. (2019) Sci Adv. 28:5. PMCID: PMC6713506

Myosin IIA-mediated forces regulate multicellular integrity during vascular sprouting.

Yoon C., Choi C., Stapleton S., Mirabella T., Howes C., Dong L., King J., Yang J., Oberai A., Eyckmans J., Chen C.S. (2019) Mol Biol Cell. 16:1974-1984. doi: 10.1091/mbc.E19-02-0076 PMCID: PMC6727772

A Bile Duct-on-a-Chip with Organ-Level Functions.

Du Y., Khandekar G., Llewellyn J., Polacheck W., Chen C.S., Wells R.G. (2019) Hepatology. 71(4), 1350-1363 doi: 10.1002/hep.30918 PMCID: PMC7048662

Microfabricated blood vessels for modeling the vascular transport barrier.

Polacheck W.J., Kutys M.L., Tefft J.L., Chen C.S. (2019) Nature Protocols 14:1425–1454. doi: 10.1038/s41596-019-0144-8 PMCID: PMC7046311

A BMP/activin A chimera is superior to native BMPs and induces bone repair in nonhuman primates when delivered in a composite matrix.

Seeherman H.J., Berasi S.P., Brown, C.T., Martinez, R.X., Juo, Z.S., Jelinsky, S., Cain, M.J., Grode, J., Tumelty, K.E., Bohner, M., Grinberg, O., Orr, N., Shoseyov, O., Eyckmans, J., Chen, C.S., Morales, P.R., Wilson, C.G., Vanderploeg, E.J., Wozney, J.M. (2019) Sci Transl Med. 11 PMID: 31019025

Studies of 3D directed cell migration enabled by direct laser writing of curved wave topography.

Cheng D., Jayne R.K., Tamborini A., Eyckmans J., White A.E., Chen C.S. (2019) Biofabrication 11:2. doi: 10.1088/1758-5090/ab047f PMID: 30721899

Sarco/endoplasmic reticulum Ca2+-ATPase is a more effective calcium remover than sodium-calcium exchanger in human embryonic stem cell-derived cardiomyocytes.

Li, S., Chopra, A., Keung, W., Chan, C. W. Y., Costa, K. D., Kong, C. -W., Hajjar, R., Chen, C.S., Li, R. A. (2019). Am J Physiol Heart Circ Physiol, 317(5), H1105-H1115. doi:10.1152/ajpheart.00540.2018 PMID: 31347915

Modeling Monogenic Diabetes using Human ESCs Reveals Developmental and Metabolic Deficiencies Caused by Mutations in HNF1A.

Cardenas-Diaz, F. L., Osorio-Quintero, C., Diaz-Miranda, M. A., Kishore, S., Leavens, K., Jobaliya, Stanescu,D., Ortiz-Gonzalez, X., Yoon, C., Chen,C.S., Haliyur, R., Brissova,M., Powers, A.C., French, D.L., Gadue, P. (2019). Cell Stem Cell, 25(2), 273-289.e5. doi:10.1016/j.stem.2019.07.007 PMCID: PMC6785828

Proliferation-independent role of NF2 (merlin) in limiting biliary morphogenesis.

Benhamouche-Trouillet, S., O'Loughlin, E., Liu, C.H., Polacheck, W., Fitamant, J., McKee, M., El-Bardeesy, N., Chen C.S., McClatchey, A. (2018). Development, 145:9. doi: 10.1242/dev.162123. PMID: 29712669

The Effects of Geometry on the Mechanics and Alignment of 3D Engineered Microtissues.

Bose P., Eyckmans J., Nguyen T.D., Chen C.S., Reich D.H. (2018) ACS Biomaterials Science & Engineering. 5: 3843−3855. doi: 10.1021/acsbiomaterials.8b01183. PMCID: PMC7001849

Extracellular matrix alignment dictates the organization of focal adhesions and directs uniaxial cell migration.

Wang W.Y., Pearson A.T., Kutys M.L., Choi C.K., Wozniak M.A., Baker B.M., Chen C.S. (2018) APL Bioengineering. 2: 046107. doi: 10.1063/1.5052239. PMCID: PMC6481732

Epstein-Barr virus-encoded EBNA2 alters immune checkpoint PD-L1 expression by downregulating miR-34a in B-cell lymphomas.

Anastasiadou E., Stroopinsky D., Alimperti S, Jiao A.L., Pyzer A.R., Cippitelli C., Pepe G., Severa M., Rosenblatt J., Etna M.P., Rieger S., Kempkes B., Coccia E.M., Ho Sui S.J., Chen C.S., Uccini S., Avigan D., Faggioni A., Trivedi P., Slack F. J. (2018) Leukemia. 33:132–147. doi: 10.1038/s41375-018-0178-x. PMCID: PMC6327052

Motile Dendritic Cells Sense and Respond to Substrate Geometry.

Bendell A.C., Anderson N., Blumenthal D., Williamson E.K., Chen C.S., Burkhardt J.K., Hammer D.A. (2018) Ann Biomed Eng. 46(9):1348-1361. doi: 10.1007/s10439-018-2041-7. PMCID: PMC6095716

Amino Acid Restriction Triggers Angiogenesis via GCN2/ATF4 Regulation of VEGF and H2S Production.

Longchamp A., Mirabella T., Arduini A., MacArthur M.R., Das A., Trevio-Villarreal J.H., Hine C., Ben-Sahra I., Knudsen N.H., Brace L.E., Reynolds J., Mejia P., Tao M., Sharma G., Wang R., Corpataux J.M., Haefliger J.A., Ahn K.H., Lee C.H., Manning B.D., Sinclair D.A., Chen C.S., Ozaki C.K., Mitchell J.R. (2018) Cell. 173(1):117-129.e14. doi:10.1016/j.cell.2018.03.001. PMCID: PMC5901681

Vascular Tissue Engineering: Progress, Challenges, and Clinical Promise.

Song H.H., Rumma R.T., Ozaki C.K., Edelman E.R., Chen C.S. (2018) Cell Stem Cell. 5;22(4):608. doi: 10.1016/j.stem.2018.03.014. PMCID: PMC5909377

Cell-geometry-dependent changes in plasma membrane order direct stem cell signalling and fate. 

von Erlach T.C., Bertazzo S., Wozniak M.A., Horejs C.M., Maynard S.A., Attwood S., Robinson B.K., Autefage H., Kallepitis C., Del Rao Hernandez A., Chen C.S., Goldoni S., Stevens M.M. (2018) Nat Mater. 17(3):237-242. doi: 10.1038/s41563-017-0014-0. PMCID: PMC5901718

Force Generation via β²-Cardiac Myosin, Titin, and α-Actinin Drives Cardiac Sarcomere Assembly from Cell-Matrix Adhesions.

Chopra, A, Kutys, M.L., Zhang, K., Polacheck, W.J., Sheng, C.C., Luu, R.J., Eyckmans, J., Hinson, J.T., Seidman, J.G., Seidman, C.E., Chen, C.S. (2018) Dev. Cell. 44(1):87-96. PMCID: PMC6421364

Laminar flow downregulates Notch activity to promote lymphatic sprouting. 

Choi, D., Park, E., Jung, E., Seong, Y.J., yoo, J., Lee, E., Hong, M., Lee, S., Ishida, H., Burford, J., Peti-Peterdi, J., Adams, R. H., Srikant, S., Gwack, Y., Chen, C.S., Vogel, H. J., Koh, C.J., Wong, A.K., Hong, Y. (2017). J Clin Invest. 127 (4): 1225-12450. doi: 10.1172/JCI87442. PMCID: PMC5373895

A non-canonical Notch complex regulates adherens junctions and vascular barrier function.

Polacheck, W.J., Kutys, M.L., Yang, J., Eyckmans, J., Wu, Y., Vasavada, H., Hirschi, K.K., Chen, C.S. (2017) Nature. 552(7684):258-262. PMCID: PMC5730479

The Arp2/3 complex binding protein HS1 is required for efficient dendritic cell random migration and force generation.

Bendell, A.C., Williamson, E.K., Chen, C.S., Burkhardt, J.K., Hammer, D.A. (2017) Integr. Biol. 9(8):695-708. PMCID: PMC5830129

3D-printed vascular networks direct therapeutic angiogenesis in ischaemia.

Mirabella, T., MacArthur, J.W., Cheng, D., Ozaki, C.K., Woo, Y.J., Yang, M.T., Chen, C.S. (2017) Nat. Biomed. Eng. 1(83) doi:10.1038/s41551-017-0083. PMCID: PMC5837070

Human Organ Chip Models Recapitulate Orthotopic Lung Cancer Growth, Therapeutic Responses, and Tumor Dormancy In Vitro.

Hassell, B.A., Goyal, G., Lee, E., Sontheimer-Phelps, A., Levy, O., Chen, C.S., Ingber, D.E. (2017) Cell Rep. 21(2):508-516. PMID: 29020635

Forces as regulators of cell adhesions.

Chen, C.S. (2017) Nat. Rev. Mol. Cell Biol. 18(12):715. PMCID: PMC7001849

Matrix degradability controls multicellularity of 3D cell migration.

Trappmann, B., Baker, B.M., Polacheck, W.J., Choi, C.K., Burdick, J.A., Chen, C.S. (2017) Nat Commun. 8(1):371. PMCID: PMC5575316

Three-dimensional biomimetic vascular model reveals a RhoA, Rac1, and N-cadherin balance in mural cell-endothelial cell-regulated barrier function.

Alimperti, S., Mirabella, T., Bajaj, V., Polacheck, W., Pirone, D.M., Duffield, J., Eyckmans, J., Assoian, R.K., Chen, C.S. (2017) Proc. Natl. Acad. Sci. USA 114(33):8758-8763. PMCID: PMC5565405

In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease.

Stevens, K.R., Scull, M.A., Ramanan, V., Fortin, C.L., Chaturvedi, R.R., Knouse, K.A., Xiao, J.W., Fung, C., Mirabella, T., Chen, A.X., McCue, M.G., Yang, M.T., Fleming, H.E., Chung, K., de Jong, Y.P., Chen, C.S., Rice, C.M., Bhatia, S.N. (2017) Sci. Transl. Med. 9(399).pii:aah5505. PMCID: PMC5896001

Designer biomaterials for mechanobiology.

Li, L., Eyckmans, J., Chen, C.S. (2017) Nat Mater. 16(12):1164-1168. PMCID: PMC7001850

Multiscale model predicts increasing focal adhesion size with decreasing stiffness in fibrous matrices.

Cao, X., Ban, E., Baker, B.M., Lin, Y., Burdick, J.A., Chen, C.S., Shenoy, V.B. (2017) Proc Natl Acad Sci USA 114(23):E4549-E4555. PMCID: PMC5468675

Cdc42 regulates branching in angiogenic sprouting in vitro.

Nguyen, D.T., Gao, L., Wong, A., Chen, C.S. (2017) Microcirculation 24(5). PMCID: PMC5505782

Cell-Cell Contact Area Affects Notch Signaling and Notch-Dependent Patterning.

Shaya, O., Binshtok, U., Hersch, M., Rivkin, D., Weinreb, S., Amir-Zilberstein, L., Khamaisi, B., Oppenheim, O., Desai, R.A., Goodyear, R.J., Richardson, G.P., Chen, C.S., Sprinzak, D. (2017) Dev Cell. 40(5):505-511. PMCID: PMC5435110

3D culture models of tissues under tension.

Eyckmans, J., Chen, C.S. (2017) J Cell Sci. 130(1):63-70. PMCID: PMC5394782

Inhibition of αvβ5 Integrin Attenuates Vascular Permeability and Protects against Renal Ischemia-Reperfusion Injury.

McCurley, A., Alimperti, S., Campos-Bilderback, S.B., Sandoval, R.M., Calvino, J.E., Reynolds, T.L., Quigley, C., Mugford, J.W., Polacheck, W.J., Gomez, I.G., Dovey, J., Marsh, G., Huang, A., Qian, F., Weinreb, P.H., Dolinski, B.M., Moore, S., Duffield, J.S., Chen, C.S., Molitoris, B.A., Violette, S.M., Crackower, M.A. (2017) J Am Soc Nephrol. 28(6):1741-1752. PMCID: PMC5461783

Non-cell autonomous cues for enhanced functionality of human embryonic stem cell-derived cardiomyocytes via maturation of sarcolemmal and mitochondrial KATP channels.

Keung, W., Ren, L., Li, S., Wong, A.O., Chopra, A., Kong, C., Tomaselli, G.F., Chen, C.S., Li, R.A. (2016).Sci Rep. 6:34154. doi: 10.1038/srep34154. PMCID: PMC5039730.

3D Biomimetic Cultures: The Next Platform for Cell Biology.

Chen, C.S. (2016) Trends in Cell Biol. 1278:1-3. PMCID: PMC5184827

Integrative Analysis of PRKAG2 Cardiomyopathy iPS and Microtissue Models Identifies AMPK as a Regulator of Metabolism, Survival, and Fibrosis.

Hinson, J.T., Chopra, A., Lowe, A., Sheng, C.C., Gupta, R.M. Kuppusamy, R., O'Sullivan, J., Rowe, G., Wakimoto, H., Gorham, J., Burke, M.A., Zhang, K., Musunuru, K., Gerszten, R.E., Wu, S.M., Chen, C.S., Seidman, J.G., Seidman, C.E. (2016) Cell Rep. 17(12):3292-3304. PMCID: PMC5193246

Differentiation alters stem cell nuclear architecture, mechanics, and mechano-sensitivity.

Heo, S.J., Driscoll, T.P., Thorpe, S.D. Nerurkar, N.L. Baker, B.M., Yang, M.T., Chen, C.S., Lee, D.A., Mauck, R.L. (2016) eLife 5:e18207. PMCID: PMC5148611