LID-PEG Project 3 will develop enhanced Siglec-8 & Siglec-9 ligands, and use them to detect and isolate counter-receptors in human lung.
Asthma and chronic obstructive pulmonary disease (COPD) are the most common inflammatory diseases of the lung. Inflammation in allergic asthma primarily targets larger airways and bronchi, and is marked by the influx of eosinophils whereas COPD involves the small airways and lung parenchyma, and is marked by the influx of neutrophils. The glycan binding protein Siglec-8 is expressed on allergic inflammatory cells (eosinophils, mast cells and basophils) whereas Siglec-9 is expressed on monocytes, neutrophils, and certain T-cells. Both suppress inflammation, and crosslinking these Siglecs on inflammatory cells induces their apoptosis, inhibits release of pro-inflammatory mediators, or enhances release of anti-inflammatory mediators, depending on the inflammatory cell type.
Glycan counter-receptors (siglec ligands) in the lung, as yet unidentified, engage Siglec-8 or Siglec-9 on inflammatory cells as a feedback mechanism to limit ongoing inflammatory disease. Each siglec counter-receptor consists of specific glycans bound to a protein or lipid carrier. The aim of this project is to isolate, identify and characterize the Siglec-8 and Siglec-9 human lung counter receptors and evaluate their expression in health and disease.
Dr. Ronald Schnaar’s research focuses on the interactions of cell surface glycans and complementary glycan binding proteins in cell-cell recognition and function. His studies on Siglec-4 in the nervous system used chemistry, biochemistry, cell biology, genetics, and animal models to translate basic discoveries in siglec-glycan recognition to potential therapies for traumatic nervous system injuries. In the area of inflammation, he has worked with Drs. Bochner and Tiemeyer to identify human neutrophil counter-receptors for the inflammatory C-type lectin, E-selectin and to define the glycan specificity of Siglec-8.
Ronald L. Schnaar
- Department of Pharmcology
Johns Hopkins School of Medicine
725 N Wolfe St
Baltimore, MD 21205-2105
- Phone: 410-955-8392