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Ronald L. Schnaar
Department Affiliation: Primary: Pharmacology and Molecular Sciences; Secondary: Neuroscience
Degree: Ph.D., Johns Hopkins University
Telephone Number: 410-955-8392
Email Address: firstname.lastname@example.org
Homepage URL: http://www.hopkinsmedicine.org/schnaar/
School of Medicine Address: 318 Wood Basic Science Building, 725 N. Wolfe Street, Baltimore, Maryland 21205
Cell surface molecular recognition in intellectual disability and Alzheimer’s disease
We explore the regulation of nervous system function at the cellular level – specifically via molecular interactions at the cell surface. Glycans (glycoproteins, glycolipids, proteoglycans) decorate all cell surfaces, and represent the most prominent class of cell surface molecules in the brain. Members of this large and varied family are ligands for complementary binding proteins on their own cell surfaces (leading to cis regulation) and on other cells (leading to cell-cell recognition). The study of cell surface glycans, glycan binding proteins, and their roles in cell physiology are part of the rapidly expanding field of GLYCOBIOLOGY. Current work in our laboratory includes two projects on NEUROGLYCOBIOLOGY. (1) Neural cells are rich in cell surface glycans called GANGLIOSIDES. Human congenital disorders of ganglioside biosynthesis invariably result in intellectual disability (ID). We are exploring cell surface (cis) ganglioside interactions that drive molecular changes related to learning and memory. (2) The immune cells of the brain, microglia, are regulated by trans interactions with glycans. Evidence indicates that these interactions regulate clearance of aggregated proteins in proteinopathies such as Alzheimer’s disease (AD). Understanding these molecular interactions may provide new therapeutic approaches to address ID and AD.
Cell surface molecular recognition in inflammatory diseases
Cell surface or extracellular glycans and glycan binding proteins initiate and regulate inflammation. In particular, glycan binding proteins of the “Siglec” family on the surface of immune cells down-regulate immune responses to resolve inflammation and keep the immune system in check. Different Siglecs on specific subsets of immune cells contact their complementary binding glycans produced by inflammatory target tissues to inhibit ongoing inflammation. Knowledge of these molecular regulatory molecules will provide novel compositions to inhibit inflammation in human diseases where inflammation is out of control (asthma, COPD).
- Nycholat, C.M., Duan, S., Knuplez, E., Worth, C., Elich, M., Yao, A., O'Sullivan, J., McBride, R., Wei, Y., Fernandes, S.M., Zhu, Z., Schnaar, R.L., Bochner, B.S., Paulson, J.C. A sulfonamide sialoside analogue for targeting Siglec-8 and -F on immune cells. J Am Chem Soc 141:14032-14037, 2019. Pub Med Reference
- Li, T.A., Schnaar, R.L. Congenital Disorders of Ganglioside Biosynthesis. Prog Mol Biol Transl Sci 156:63-82, 2018. Pub Med Reference
- Gonzalez-Gil, A., Porell, R.N., Fernandes, S.M., Wei, Y., Yu, H., Carroll, D.J., McBride, R., Paulson, J.C., Tiemeyer, M., Aoki, K., Bochner, B.S., Schnaar, R.L. Sialylated keratan sulfate proteoglycans are Siglec-8 ligands in human airways. Glycobiology 28:786-801, 2018. Pub Med Reference
- Yu, H., Gonzalez-Gil, A., Wei, Y., Fernandes, S.M., Porell, R.N., Vajn, K., Paulson, J.C., Nycholat, C.M., Schnaar, R.L. Siglec-8 and Siglec-9 binding specificities and endogenous airway ligand distributions and properties. Glycobiology 27:657-668, 2017. Pub Med Reference
- Schnaar, R.L. Glycobiology simplified: diverse roles of glycan recognition in inflammation. J Leukoc Biol 98:825-838, 2016. Pub Med Reference
- Schnaar, R.L. Gangliosides of the vertebrate nervous system. J Mol Biol 428:3325-3336, 2016. Pub Med Reference
- Schleimer, R.P., Schnaar, R.L., Bochner, B.S. Regulation of airway inflammation by Siglec-8 and Siglec-9 sialoglycan ligand expression. Curr Opin Allergy Clin Immunol. 16:24-30, 2016. Pub Med Reference
- Yoo, S.W., Motari, M.G., Susuki, K., Prendergast, J., Mountney, A., Hurtado, A., Schnaar, R.L. Sialylation regulates brain structure and function. FASEB J. 29:3040-3053, 2015. Pub Med Reference
- Jia, Y., Yu, H., Fernandes, S.M., Wei, Y., Gil, A.G., Motari, M.G., Vajn, K., Stevens, W.W., Peters, A.T., Bochner, B.S., Kern, R.C., Schleimer, R.P., Schnaar, R.L. Expression of ligands for Siglec‑8 and Siglec-9 in human airways and airway cells. J. Allergy Clin. Immunol. 135:799-810, 2015. Pub Med Reference
Other graduate programs in which Dr. Schnaar participates: