CC, ERGUL The projects in this Program Project Grant application focus on two key damage associated molecular patterns (DAMPs), high mobility group box 1 (HMGB1) and mitochondrial (mt) DNA, activating the innate immune response via their respective pattern recognition receptors (PPRs) TLR4 and TLR9 resulting in stimulation of a number of cytokines in experimental animal models of hypertension. The Bioinflammation Core (Core C) is structured to serve all three projects with centralized measurements of DAMPs, PRRs, immune cells and downstream cytokines to facilitate the success of the individual projects and achieve the overall goals of this Program Project. The secondary goal is to provide necessary services to enhance the synergy among projects. Core C will be directed by Dr. Ergul and supported by Dr. Babak Baban. Both investigators have a long- standing record of analyzing experimental and clinical specimens with a highly qualified staff. A centralized Core is essential to the success of each project and the Program Project as a whole and offers the following benefits: 1. The coordination of sample preparation within the Bioinflammation Core C will benefit all Projects as Core C will optimize sample recovery and increase efficiency and rigor by allowing analysis of more samples in one run while providing blinded analyses of the samples. 2. Common approach (in many cases identical methods and reagents) to measure the same markers across the projects will provide synergy, quality control and consistency among the projects. 3. The measurement of primary and secondary DAMPs/PRRS in all Projects will cross cultivate the Projects and allow the development of new venues of investigation that otherwise would not have been possible with regular R01 applications. 4. Higher numbers of measurements will be completed at a relatively lower cost with highly skilled research personnel. 5. A close interaction with the Animal Models Core (Core B) will ensure proper collection and storage of specimens and increase reproducibility.
CC, ERGUL Uncontrolled hypertension increases the risk of chronic kidney disease, stroke, heart attack, heart failure and peripheral artery disease and in ~85% of cases, the cause of hypertension remains unknown. The proposed project (Core C) will provide centralized measurements and provide quality control for 3 projects in the program project addressing novel immune mechanisms that may contribute to the development and consequences of hypertension.
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