Assistant Professor
Wayne State University-School of Medicine (Pharmacology) and Functional Fluidics
Wayne State University-School of Medicine
Detroit, Michigan, United States
Jennell White
Wayne State University School of Medicine
Department of Pharmacology
Assistant Professor (Research)
Functional Fluidics
Director of Scientific Research and Regulatory Affairs
Red blood cells (RBCs) contribute to vaso-occlusive episodes (VOEs) in sickle cell disease (SCD) by participating in a series of adhesive events mediated by cell surface adhesion molecules elevated in the SCD microenvironment. Hydroxyurea (HU), the standard of care for SCD management, reduces VOEs, in part, by decreasing adhesion receptor expression and RBC-endothelial interactions. Erythroid signaling pathways involved in the regulation of vaso-occlusive adhesive events are poorly understood. VLA-4, one of the best characterized adhesion receptors in SCD, supports avid interactions to endothelial VCAM-1. High levels of very late antigen-4 (VLA-4) and vascular cell adhesion molecule-1 (VCAM-1) have been associated with VOEs and severe disease phenotypes.
Published work established VLA-4-mediated adhesion is significantly lower in SCD subjects on SCD-modifying therapies and increased during VOEs. Also, SCD subjects with high frequency VOEs have a pro-adhesive phenotype at steady state and experience a higher frequency of vaso-occlusive events two years prospectively. Others have shown that VLA-4-dependent adhesive interactions are rapidly and reversibly modulated by cell signaling pathways that alter VLA-4 activity/binding affinity to VCAM-1. More recently, we have shown that, within minutes, HU reduces VLA-4-mediated activation and adhesion to VCAM-1 in sickle reticulocytes, suggesting rapid erythroid signaling pathways are involved. Other studies have corroborated that cell signaling pathways activate VLA-4 to provide additional adhesivity to VCAM-1 however, these mechanisms are not been well defined in red cell adhesion in SCD.
Our lab utilizes flow cytometry, mass spectrometry, and micriofluidics to assess adhesion receptor expression/activation, identify erythroid signaling pathways regulating red-cell endotyhelial interactions, and measure sickle cell adhesion to endothelial/protein substractes, respectively.
Disclosure information not submitted.
Real-World Assessment of Red Blood Cell (RBC) Health Biomarkers in Sickle Cell Disease (SCD)
Sunday, June 9, 2024
3:30 PM – 3:45 PM ET