(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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Special Emphasis Panel (ZHL1-CSR-H (F1))
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Danthi, Narasimhan
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Cleveland Clinic Lerner
Other Basic Sciences
Schools of Medicine
United States
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Schnellmann, Rahel; Sack, Ragna; Hess, Daniel et al. (2018) A Selective Extracellular Matrix Proteomics Approach Identifies Fibronectin Proteolysis by A Disintegrin-like and Metalloprotease Domain with Thrombospondin Type 1 Motifs (ADAMTS16) and Its Impact on Spheroid Morphogenesis. Mol Cell Proteomics 17:1410-1425
Mead, Timothy J; Du, Yaoyao; Nelson, Courtney M et al. (2018) ADAMTS9-Regulated Pericellular Matrix Dynamics Governs Focal Adhesion-Dependent Smooth Muscle Differentiation. Cell Rep 23:485-498
Cikach, Frank S; Koch, Christopher D; Mead, Timothy J et al. (2018) Massive aggrecan and versican accumulation in thoracic aortic aneurysm and dissection. JCI Insight 3:
Sivakumar, Aravind; Mahadevan, Aparna; Lauer, Mark E et al. (2018) Midgut Laterality Is Driven by Hyaluronan on the Right. Dev Cell 46:533-551.e5
Kim, Yeojung; West, Gail A; Ray, Greeshma et al. (2018) Layilin is critical for mediating hyaluronan 35kDa-induced intestinal epithelial tight junction protein ZO-1 in vitro and in vivo. Matrix Biol 66:93-109
Sikes, Katie J; Renner, Kristen; Li, Jun et al. (2018) Knockout of hyaluronan synthase 1, but not 3, impairs formation of the retrocalcaneal bursa. J Orthop Res 36:2622-2632
Kessler, Sean P; Obery, Dana R; Nickerson, Kourtney P et al. (2018) Multifunctional Role of 35 Kilodalton Hyaluronan in Promoting Defense of the Intestinal Epithelium. J Histochem Cytochem 66:273-287
Chen, Jee-Wei E; Pedron, Sara; Shyu, Peter et al. (2018) Influence of Hyaluronic Acid Transitions in Tumor Microenvironment on Glioblastoma Malignancy and Invasive Behavior. Front Mater 5:
Ni, Kevin; Gill, Amar; Tseng, Victor et al. (2018) Rapid clearance of heavy chain-modified hyaluronan during resolving acute lung injury. Respir Res 19:107
Prins, Bram P; Mead, Timothy J; Brody, Jennifer A et al. (2018) Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6. Genome Biol 19:87

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