Thomas H Barker

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Primary Appointment

Professor, Biomedical Engineering

Education

  • PhD, Biomedical Engineering, University of Alabama, Birmingham

Research Disciplines

Biomedical Engineering, Cell and Developmental Biology, Development, Stem Cells & Regeneration, Experimental Pathology

Research Interests

Matrix Biology and Engineering

Research Description

My lab is primarily focused on both understanding and manipulating cell-ECM mechanotransduction pathways in homeostasis and disease. Our primary interest is in understanding how cells' changing microenvironment direct their phenotype and initiate pathological programs, primarily tissue fibrosis and scar formation. Both cells and their extracellular matrix (ECM) are exquisitely sensitive to mechanical forces and slight perturbations in the mechanical homeostasis between cells and their ECM can initiate pathological programs that lead to tissue destruction and even death. For example, pulmonary fibrosis is a fatal disease driven in large part by stiffening of lung tissue due to chronic wound repair. Once the tissue becomes stiff, normal cells are recruited into a pathological program that ultimately leads to complete destruction of the lung and death of the patient. There are no cures and very few viable medical options for treating the disease. For these reasons, understanding how the fibrotic program is both initiated and persists will lead to new breakthroughs in treating these fatal diseases.

Personal Statement

"We develop therapeutics to fibrosis, or scar formation. While scars of the skin might be unsightly, scars in organs, like the lung, kill people."
THOMAS H. BARKER, PROFESSOR
Dr. Barker is a Professor in Biomedical Engineering in the Schools of Engineering and Medicine at the University of Virginia. He performed his academic and scientific training with Drs. James Hagood, Joanne Murhpy-Ullrich, Helene Sage, and Jeffrey Hubbell prior to his first faculty post at Georgia Institute of Technology, where he spend 10 years as an Assistant and Associate Professor. Dr. Barkerâs research integrates engineering and quantitative approaches with basic cell and molecular biology to understand and control cell phenotype through their interactions with natural and engineered extracellular matrices. Dr. Barker is also focused on understanding the fundamental roles of cell mechanotransduction and mechanical forces in regulating the biochemical activity of proteins in the extracellular matrix toward wound repair, regeneration, and fibrosis. Dr. Barker has established a number of fundamental systems based on rational mutagenesis, molecular evolution of extracellular matrix protein fragments and antibodies that allow both basic biochemical and cell biological studies on the ECM and detection and treatment of organ fibrosis. Dr. Barker has co-authored research and review papers in leading cell biology, matrix biology, and biomaterials journals, he received the NIH Directorâs Transformative Research Award in 2015. Dr. Barker was also the recipient of the American Society for Matrix Biologyâs Young Investigator Award in 2012 and Iozzo Award in 2016.

Training

  • Basic Cardiovascular Research Training Grant
  • Biotechnology Training Grant
  • Cancer Research Training in Molecular Biology

Selected Publications

2024

Nellenbach, K., Mihalko, E., Nandi, S., Koch, D. W., Shetty, J., Moretti, L., . . . Brown, A. C. (2024). Ultrasoft platelet-like particles stop bleeding in rodent and porcine models of trauma.. Science translational medicine, 16(742), eadi4490. doi:10.1126/scitranslmed.adi4490

Younesi, F. S., Miller, A. E., Barker, T. H., Rossi, F. M. V., & Hinz, B. (2024). Fibroblast and myofibroblast activation in normal tissue repair and fibrosis.. Nature reviews. Molecular cell biology. doi:10.1038/s41580-024-00716-0

2023

Hu, P., Miller, A. E., Yeh, C. -R., Bingham, G. C., Civelek, M., & Barker, T. H. (2023). SEMA7a primes integrin α581 engagement instructing fibroblast mechanotransduction, phenotype and transcriptional programming. MATRIX BIOLOGY, 121, 179-193. doi:10.1016/j.matbio.2023.06.006

2022

Cook, C. J., Miller, A. E., Barker, T. H., Di, Y., & Fogg, K. C. (2022). Characterizing the extracellular matrix transcriptome of cervical, endometrial, and uterine cancers.. Matrix biology plus, 15, 100117. doi:10.1016/j.mbplus.2022.100117

Hata, A., Guo, Y., Miller, A. E., Hata, M., Mei, Z., Manafi, A., . . . Krupnick, A. S. (2022). Loss of stromal cell Thy-1 plays a critical role in lipopolysaccharide induced chronic lung allograft dysfunction. JOURNAL OF HEART AND LUNG TRANSPLANTATION, 41(8), 1044-1054. doi:10.1016/j.healun.2022.05.009

Hu, P., Leyton, L., Hagood, J. S., & Barker, T. H. (2022). Thy-1-Integrin Interactions in cis and Trans Mediate Distinctive Signaling. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 10. doi:10.3389/fcell.2022.928510

2021

Moretti, L., Stalfort, J., Barker, T. H., & Abebayehu, D. (2022). The interplay of fibroblasts, the extracellular matrix, and inflammation in scar formation. JOURNAL OF BIOLOGICAL CHEMISTRY, 298(2). doi:10.1016/j.jbc.2021.101530

Hannan, R. T., Miller, A. E., Hung, R. -C., Sano, C., Peirce, S. M., & Barker, T. H. (2021). Extracellular matrix remodeling associated with bleomycin-induced lung injury supports pericyte-to-myofibroblast transition.. Matrix biology plus, 10, 100056. doi:10.1016/j.mbplus.2020.100056

Zhang, Y., Zhang, Y., Kameishi, S., Barutello, G., Zheng, Y., Tobin, N. P., . . . Holmgren, L. (2021). The Amot/integrin protein complex transmits mechanical forces required for vascular expansion. CELL REPORTS, 36(8). doi:10.1016/j.celrep.2021.109616

Hui, E., Moretti, L., Barker, T. H., & Caliari, S. R. (2021). The Combined Influence of Viscoelastic and Adhesive Cues on Fibroblast Spreading and Focal Adhesion Organization. CELLULAR AND MOLECULAR BIOENGINEERING, 14(5), 427-440. doi:10.1007/s12195-021-00672-1

Yeh, C. -R., Bingham, G. C., Shetty, J., Hu, P., & Barker, T. H. (2021). Decellularized Extracellular Matrix (ECM) as a Model to Study Fibrotic ECM Mechanobiology. MYOFIBROBLASTS, 2299, 237-261. doi:10.1007/978-1-0716-1382-5_18

Nandi, S., Mihalko, E., Nellenbach, K., Castaneda, M., Schneible, J., Harp, M., . . . Brown, A. C. (2021). Synthetic Platelet Microgels Containing Fibrin Knob B Mimetic Motifs Enhance Clotting Responses. ADVANCED THERAPEUTICS, 4(5). doi:10.1002/adtp.202100010

2020

Leonard-Duke, J., Evans, S., Hannan, R. T., Barker, T. H., Bates, J. H. T., Bonham, C. A., . . . Peirce, S. M. (2020). Multi-scale models of lung fibrosis. MATRIX BIOLOGY, 91-92, 35-50. doi:10.1016/j.matbio.2020.04.003

Melchor, S. J., Hatter, J. A., Castillo, E. A. L., Saunders, C. M., Byrnes, K. A., Sanders, I., . . . Ewald, S. E. (2020). T. gondii infection induces IL-1R dependent chronic cachexia and perivascular fibrosis in the liver and skeletal muscle. SCIENTIFIC REPORTS, 10(1). doi:10.1038/s41598-020-72767-0

DeLeon-Pennell, K. Y., Barker, T. H., & Lindsey, M. L. (2020). Fibroblasts: The arbiters of extracellular matrix remodeling. MATRIX BIOLOGY, 91-92, 1-7. doi:10.1016/j.matbio.2020.05.006

Bingham, G. C., Lee, F., Naba, A., & Barker, T. H. (2020). Spatial-omics: Novel approaches to probe cell heterogeneity and extracellular matrix biology. MATRIX BIOLOGY, 91-92, 152-166. doi:10.1016/j.matbio.2020.04.004

Miller, A. E., Hu, P., & Barker, T. H. (2020). Feeling Things Out: Bidirectional Signaling of the Cell-ECM Interface, Implications in the Mechanobiology of Cell Spreading, Migration, Proliferation, and Differentiation. ADVANCED HEALTHCARE MATERIALS, 9(8). doi:10.1002/adhm.201901445

2019

Witherel, C. E., Abebayehu, D., Barker, T. H., & Spiller, K. L. (2019). Macrophage and Fibroblast Interactions in Biomaterial-Mediated Fibrosis. ADVANCED HEALTHCARE MATERIALS, 8(4). doi:10.1002/adhm.201801451

Guo, Y., Wang, Q., Li, D., Onyema, O. O., Mei, Z., Manafi, A., . . . Krupnick, A. S. (2019). Vendor-specific microbiome controls both acute and chronic murine lung allograft rejection by altering CD4+Foxp3+ regulatory T cell levels. AMERICAN JOURNAL OF TRANSPLANTATION, 19(10), 2705-2718. doi:10.1111/ajt.15523

Stefanelli, V. L., Choudhury, S., Hu, P., Liu, Y., Schwenzer, A., Yeh, C. -R., . . . Barker, T. H. (2019). Citrullination of fibronectin alters integrin clustering and focal adhesion stability promoting stromal cell invasion. MATRIX BIOLOGY, 82, 86-104. doi:10.1016/j.matbio.2019.04.002

Hu, P., & Barker, T. H. (2019). Thy-1 in Integrin Mediated Mechanotransduction. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 7. doi:10.3389/fcell.2019.00022

2018

Chambers, D. M., Moretti, L., Zhang, J. J., Cooper, S. W., Chambers, D. M., Santangelo, P. J., & Barker, T. H. (2018). LEM domain-containing protein 3 antagonizes TGFβ-SMAD2/3 signaling in a stiffness-dependent manner in both the nucleus and cytosol. JOURNAL OF BIOLOGICAL CHEMISTRY, 293(41), 15867-15886. doi:10.1074/jbc.RA118.003658

Welsch, N., Brown, A. C., Barker, T. H., & Lyon, L. A. (2018). Enhancing clot properties through fibrin-specific self-cross-linked PEG side-chain microgels. COLLOIDS AND SURFACES B-BIOINTERFACES, 166, 89-97. doi:10.1016/j.colsurfb.2018.03.003

Yamauchi, M., Barker, T. H., Gibbons, D. L., & Kurie, J. M. (2018). The fibrotic tumor stroma. JOURNAL OF CLINICAL INVESTIGATION, 128(1), 16-25. doi:10.1172/JCI93554

Fiore, V. F., Wong, S. S., Tran, C., Tan, C., Xu, W., Sulchek, T., . . . Barker, T. H. (2018). αvβ3 Integrin drives fibroblast contraction and strain stiffening of soft provisional matrix during progressive fibrosis. JCI INSIGHT, 3(20). doi:10.1172/jci.insight.97597

Hay, J. J., Rodrigo-Navarro, A., Petaroudi, M., Bryksin, A. V., Garcia, A. J., Barker, T. H., . . . Salmeron-Sanchez, M. (2018). Bacteria-Based Materials for Stem Cell Engineering. ADVANCED MATERIALS, 30(43). doi:10.1002/adma.201804310

Hardy, E. T., Wang, Y. J., Iyer, S., Mannino, R. G., Sakurai, Y., Barker, T. H., . . . Lam, W. A. (2018). Interdigitated microelectronic bandage augments hemostasis and clot formation at low applied voltage in vitro and in vivo. LAB ON A CHIP, 18(19), 2985-2993. doi:10.1039/c8lc00573g

Kim, D. J., Dunleavey, J. M., Xiao, L., Ollila, D. W., Troester, M. A., Otey, C. A., . . . Dudley, A. C. (2018). Suppression of TGFβ-mediated conversion of endothelial cells and fibroblasts into cancer associated (myo) fibroblasts via HDAC inhibition. BRITISH JOURNAL OF CANCER, 118(10), 1359-1368. doi:10.1038/s41416-018-0072-3

2017

Li, S., Nih, L. R., Bachman, H., Fei, P., Li, Y., Nam, E., . . . Segura, T. (2017). Hydrogels with precisely controlled integrin activation dictate vascular patterning and permeability. NATURE MATERIALS, 16(9), 953-+. doi:10.1038/NMAT4954

Cao, L., Nicosia, J., Larouche, J., Zhang, Y., Bachman, H., Brown, A. C., . . . Barker, T. H. (2017). Detection of an Integrin-Binding Mechanoswitch within Fibronectin during Tissue Formation and Fibrosis. ACS NANO, 11(7), 7110-7117. doi:10.1021/acsnano.7b02755

Hannan, R. T., Peirce, S. M., & Barker, T. H. (2018). Fibroblasts: Diverse Cells Critical to Biomaterials Integration. ACS BIOMATERIALS SCIENCE & ENGINEERING, 4(4), 1223-1232. doi:10.1021/acsbiomaterials.7b00244

Douglas, A. M., Fragkopoulos, A. A., Gaines, M. K., Lyon, L. A., Fernandez-Nieves, A., & Barker, T. H. (2017). Dynamic assembly of ultrasoft colloidal networks enables cell invasion within restrictive fibrillar polymers. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 114(5), 885-890. doi:10.1073/pnas.1607350114

Barker, T. H., & Engler, A. J. (2017). The provisional matrix: setting the stage for tissue repair outcomes. MATRIX BIOLOGY, 60-61, 1-4. doi:10.1016/j.matbio.2017.04.003

Hyatt, J. S., Douglas, A. M., Stanley, C., Do, C., Barker, T. H., & Fernandez-Nieves, A. (2017). Charge segregation in weakly ionized microgels. PHYSICAL REVIEW E, 95(1). doi:10.1103/PhysRevE.95.012608

2014

Qiu, Y., Brown, A. C., Myers, D. R., Sakurai, Y., Mannino, R. G., Tran, R., . . . Lam, W. A. (2014). Platelet mechanosensing of substrate stiffness during clot formation mediates adhesion, spreading, and activation.. Proceedings of the National Academy of Sciences of the United States of America, 111(40), 14430-14435. doi:10.1073/pnas.1322917111

2012

Huang, X., Yang, N., Fiore, V. F., Barker, T. H., Sun, Y., Morris, S. W., . . . Zhou, Y. (2012). Matrix Stiffness-Induced Myofibroblast Differentiation Is Mediated by Intrinsic Mechanotransduction. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 47(3), 340-348. doi:10.1165/rcmb.2012-0050OC