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Roles of Red Blood Cell Derived Extracellular Vesicles in Complement Activation and Thromboinflammation in sickle cell disease

US · IL NIH grant awarded #nih-5K25HL159358-04

Summary

This project aims to understand the roles of red blood cell-derived extracellular vesicles (REVs) in complement activation and thromboinflammation in sickle cell disease (SCD) and to develop REVs as biomarkers for disease activity and therapeutic response.

What they want

The project proposes three aims: 1) Determine the responses of SCD red blood cells and the complement system to various stresses (shear, hypoxia, hypoxia-reoxygenation) using microfluidic systems, characterizing autologous and endogenous REVs for surface protein expression, proteomic content, and effect on complement activation. 2) Elucidate the roles of REVs and complement system activation in thromboinflammation by assessing REV-mediated endothelial activation and complement activation using analytical and functional endpoints like cellular adhesion and thrombus formation. 3) Utilize analytical and functional assays with endogenous and autologous REVs to assess and predict clinical outcomes and therapeutic efficacies for individual patients, establishing a temporal and progressive database of REV-initiated complement activation and thromboinflammation.
Deliverables
  • Mechanistic understanding of stress-induced complement system activation and REV generation
  • Characterization of autologous and endogenous REVs (surface protein expression, proteomic content)
  • Elucidation of REV and complement system roles in thromboinflammation
  • Analytical and functional assays for assessing and predicting clinical outcomes and therapeutic efficacies
  • Temporal and progressive database of REV-initiated complement activation and thromboinflammation
Technical requirements
  • Microfluidic systems
  • Functional assays
  • Analytical assays
  • Surface protein expression definition
  • Proteomic content analysis
Roles of Red Blood Cell Derived Extracellu…
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