Mechanotransduction In Disease: More Than Just Stiffness
Thomas Barker, Ph.D.
Professor of Biomedical Engineering and Cell Biology
Director, UVA Fibrosis Institute
Schools of Engineering and Medicine
University of Virginia
Friday, January 24
12 - 1 P.M.
Bryan Research 103
Abstract
Since the late 1990s, the cell biology and bioengineering communities have been both inspired by and driven to understand how the mechanics or physics of the microenvironment impact fundamental cell behaviors, from proliferation to migration and differentiation. Microenvironmental mechanics are now known to play pivotal roles in tissue development, homeostasis and disease; perhaps none as clearly as in tissue fibrosis where the unregulated remodeling and elaboration of extracellular matrix establishes an unvirtuous feedback loop whereby the stiffening microenvironment drives myofibroblast differentiation and thus further matrix elaboration. My lab has focused on the dynamic reciprocity between fibroblasts, the arbiter of tissue remodeling, and their extracellular matrix microenvironment. Although we have found significant evidence in support of canonical stiffness-driven fibroblast activation and protomyofibroblast differentiation, recent findings from the lab highlight far greater complexities in fibroblast-matrix communication that establish tissue state. I will present multiple vignettes from our recent work that shed light on 1) an integrin adaptor protein, Thy-1, the absence of which classifies a disease relevant fibroblast subpopulation that is both insensitive to matrix stiffness and activated in soft microenvironments and 2) how posttranslational modifications of the provisional matrix protein fibronectin add another level of complexity to our understanding of cell-matrix mechanotransduction in the context of disease.
Biography
Dr. Barker is a Full Professor in the Departments of Biomedical Engineering and Cell Biology at the University of Virginia and the Director of the UVA Fibrosis Initiative. Dr. Barker received his Bachelor of Science in Chemistry and Physics in 1995 from Oglethorpe University in Atlanta, GA and his Ph.D. in Biomedical Engineering from the University of Alabama at Birmingham in 2003, working under Drs. Gerry Fuller and James Hagood. Dr. Barker performed two postdoctoral fellowships in the labs of Dr. Helene Sage at the University of Washington and Dr. Jeffrey Hubbell at the École Polytéchnique de Lausanne. He was an Assistant and Associate Professor in the joint GA Tech/Emory Univ. Biomedical Engineering until 2016, when he took the position of Professor and Director at the University of Virginia.
Dr. Barker’s research activities center cell-extracellular matrix biology, mechanobiology, and biotechnology focused primarily on fibroblast-ECM interactions that drive tissue repair, regeneration, and fibrosis. His research integrates engineering applications and basic cell and molecular biology approaches to understand and control cell phenotype through cell engineering/synthetic biology and ECM engineering. Dr. Barker has co-authored 70+ research and review papers in leading cell biology, matrix biology, and biomaterials journals and has received funding from the Coulter Foundation, NIH, DOD, and Health Effects Institute. He received both the Young Investigator Award (2012) and the top research award, the Iozzo Award (2016), from the American Society for Matrix Biology and received the NIH Director’s Transformative Research Award in 2015.