The Core C microarray core facility supports the proposed project aims to address the central hypothesis of the program, as stated that Protein glycosylation and glycoprotein remodeling modulate the coagulopathy and inflammation of sepsis. Core C provides unique technological capabilities and high throughput microarray analyses of blood-derived experimental samples to most effectively achieve the research aims of all three projects. Core C has developed a rapid and sensitive microarray-based analytical technology using immobilized lectins to detect changes in glycan linkages in biological fluids. This lectin microarray has detected the remodeling of glycoproteins in the blood during sepsis that includes the appearance of asialoglycoproteins coincident with the expression of host and pathogen neuraminidases. The glycan linkages of circulating and vascular glycoproteins including the proteoglycans have recently been found to play significant roles in the pathogenesis of inflammation and coagulopathy during sepsis. Core C will undertake studies designed by the projects to investigate these newly discovered changes to blood glycoproteins that are activated in the host and which modulate the coagulopathy and inflammation of sepsis. In parallel, Core C will provide a custom antibody-based microarray to detect changes in selected circulating proteins that are under study by the projects as well as those known to participate in the onset of inflammation that can lead to extensive vascular and organ damage during sepsis. Analyses provided by by Core C will compare and quantify these changes in the blood during sepsis as well as in the non-microbial Systemic Inflammatory Response Syndrome. As detailed in the Core C Research Strategy, Core C will accomplish lectin and antibody microarray analyses of blood plasma samples from mice and humans, accomplish hematology data profiling of blood samples from mice and humans, and determine pathogen colony forming unit measurements of blood samples when requested. As with mouse plasma samples provided by the projects, Core C will analyze human plasma for changes in glycan linkages among secreted proteins as well as compare the abundance of inflammatory markers. Core C microarray assays include plasma measurements of heparan sulfate proteoglycans that have recently been found to modulate the inflammation and coagulopathy in sepsis. Core C will enhance the rate of progress of program research and facilitate research integration and synergies among the studies proposed. Although analyses of blood and blood components remain the focus of Core C activity, the Core C core facility can extend screening capabilities to other biological fluids if needed.

Public Health Relevance

This core facility supports multiple research projects investigating recent discoveries pertaining to the pathogenesis of sepsis, which is a frequently lethal syndrome afflicting millions of people each year in the U.S. and costing many billions of dollars in health care . Support provided by this core facility will enable project research goals focused on the debilitating and often lethal complications of sepsis that arise from host inflammation and coagulopathy.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL131474-02
Application #
9315204
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Sarkar, Rita
Project Start
Project End
Budget Start
2017-05-01
Budget End
2018-04-30
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Sanford Burnham Prebys Medical Discovery Institute
Department
Type
DUNS #
020520466
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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