(Overview, Hascall) Program Introduction and Objectives - The 5 projects in our PEG, Hyaluronan Matrices in Vascular Pathologies, explore the emerging central role that hyaluronan (HA)-based matrices have in vascular development and inflammatory pathologies of the vasculature. Members of the Research Team have already collaborated and pioneered the initial research with this matrix and its dialogue with inflammatory cells. We now propose to focus in depth on novel investigations that further investigate the HA matrix and its interactions with leukocytes in vasculopathies related to diabetes (Project 1), wound healing (Project 2), inflammatory bowel disease (Project 3), pulmonary hypertension (Project 4), and glycocalyx/pericellular matrix modification in vascular development (Project 5). The existing synergy of the Research Team is established by the co-authorship of papers in the biosketches, by new collaborations, and by the crosstalk between the aims of the projects and the methods employed. During the course of the PEG, each project will recruit two junior investigators (graduate student, medical student, or postdoctoral fellow) who will receive glycoscience and glycotechnology training through the enrichment course described in the Glycosciences Skills Development Core C and by attending courses at the Complex Carbohydrate Research Center at the University of Georgia. Shared Resource Core B will provide all projects with comprehensive analyses to determine the amounts, sizes, fine structures, and modifications of glycosaminoglycans, and will prepare tissues for sectioning and staining for HA and relevant matrix molecules. Shared Resource Core B will work with Glycosciences Skills Development Core C to provide training for the junior investigators in these techniques with emphasis on their project-related experiments. The Administration Core will provide overall leadership for the PEG and coordinate the biweekly meetings of the investigators in the Research Teams to discuss ongoing experimental results and plan future experiments. Biannual meetings of the Internal Advisory Board, and visits by the Visiting Scholars and members of an External Advisory Board will review progress, provide project guidance, and enrich scholarly activities within the PEG.
Vascular tissues and circulating leukocytes are involved in essentially all inflammatory processes. Thus, understanding the mechanisms involved in synthesizing the monocyte-adhesive hyaluronan matrix and the responses of inflammatory cells that interact with it, offers to provide a central paradigm for most inflammatory processes and subsequent pathologies.
|Kim, Yeojung; West, Gail A; Ray, Greeshma et al. (2017) Layilin is critical for mediating hyaluronan 35kDa-induced intestinal epithelial tight junction protein ZO-1 in vitro and in vivo. Matrix Biol :|
|Kessler, Sean P; Obery, Dana R; Nickerson, Kourtney P et al. (2017) Multifunctional Role of 35 Kilodalton Hyaluronan in Promoting Defense of the Intestinal Epithelium. J Histochem Cytochem :22155417746775|
|Saikia, Paramananda; Bellos, Damien; McMullen, Megan R et al. (2017) MicroRNA 181b-3p and its target importin ?5 regulate toll-like receptor 4 signaling in Kupffer cells and liver injury in mice in response to ethanol. Hepatology 66:602-615|
|Zahreddine, Hiba Ahmad; Culjkovic-Kraljacic, Biljana; Emond, Audrey et al. (2017) The eukaryotic translation initiation factor eIF4E harnesses hyaluronan production to drive its malignant activity. Elife 6:|
|Ghatak, Shibnath; Markwald, Roger R; Hascall, Vincent C et al. (2017) Transforming growth factor ?1 (TGF?1) regulates CD44V6 expression and activity through extracellular signal-regulated kinase (ERK)-induced EGR1 in pulmonary fibrogenic fibroblasts. J Biol Chem 292:10465-10489|
|Petrey, Aaron C; de la Motte, Carol A (2017) The extracellular matrix in IBD: a dynamic mediator of inflammation. Curr Opin Gastroenterol 33:234-238|
|Ghatak, Shibnath; Hascall, Vincent C; Markwald, Roger R et al. (2017) Transforming growth factor ?1 (TGF?1)-induced CD44V6-NOX4 signaling in pathogenesis of idiopathic pulmonary fibrosis. J Biol Chem 292:10490-10519|
|Asano, Keiichi; Nelson, Courtney M; Nandadasa, Sumeda et al. (2017) Stromal Versican Regulates Tumor Growth by Promoting Angiogenesis. Sci Rep 7:17225|
|Hendee, Kathryn; Wang, Lauren Weiping; Reis, Linda M et al. (2017) Identification and functional analysis of an ADAMTSL1 variant associated with a complex phenotype including congenital glaucoma, craniofacial, and other systemic features in a three-generation human pedigree. Hum Mutat 38:1485-1490|
|Stober, Vandy P; Johnson, Collin G; Majors, Alana et al. (2017) TNF-stimulated gene 6 promotes formation of hyaluronan-inter-?-inhibitor heavy chain complexes necessary for ozone-induced airway hyperresponsiveness. J Biol Chem 292:20845-20858|
Showing the most recent 10 out of 109 publications