(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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL107147-03
Application #
8494077
Study Section
Special Emphasis Panel (ZHL1-CSR-H (F1))
Program Officer
Danthi, Narasimhan
Project Start
2011-07-01
Project End
2018-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
3
Fiscal Year
2013
Total Cost
$2,175,403
Indirect Cost
$774,865
Name
Cleveland Clinic Lerner
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
135781701
City
Cleveland
State
OH
Country
United States
Zip Code
44195
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