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Department Affiliation: Primary: Pharmacology and Molecular Sciences; Secondary: Neuroscience
Degree: Ph.D., Johns Hopkins University
Telephone Number: 410-955-8392
Fax Number: 410-955-3023
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-cell interactions in the nervous system
We explore the mechanisms nerve cells use to communicate with each other when they come into contact. Cell-cell recognition occurs when complementary molecules on apposing cell surfaces meet. A receptor on one cell surface binds to its ligand on a nearby cell, initiating a cascade of events that regulate cell behaviors ranging from simple adhesion to complex cellular differentiation. Glycans (glycoproteins, glycolipids, proteoglycans) decorate all cell surfaces, and represent the most prominent class of cell surface molecules. Members of this large and varied family are ligands for complementary binding proteins, lectins, on nearby cells. Lectin-carbohydrate interactions mediate cell-cell interactions throughout the body. The study of cell surface glycans, lectins, and their roles in cell physiology are part of the rapidly expanding field of GLYCOBIOLOGY. Current work in our laboratory focuses on NEUROGLYCOBIOLOGY. Neural cells are rich in cell surface glycans called GANGLIOSIDES. Major members of the ganglioside family are ligands for the important cell recognition protein "MYELIN-ASSOCIATED GLYCOPROTEIN" (MAG). MAG binds to gangliosides on nerve cells to initiate cell-cell recognition that is essential to the stability and health of axons, but MAG also blocks AXON REGENERATION after nervous system injury. Understanding these molecular interactions provides new therapeutic approaches to protect axons and promote nerve regeneration after injury.
Cell-cell interactions in inflammation
Inflammation occurs when circulating white blood cells bind to vascular endothelial cells and invade the underlying tissues. The first step in inflammation is mediated by endothelial lectins called SELECTINS, which bind to glycans on white blood cells. In collaborative studies we isolated selectin-binding gangliosides from human neutrophils, the most abundant white blood cells, and determined their structures and functions. Defining endogenous glycans responsible for initiating neutrophil-endothelial interactions may reveal new ways to control inflammation. In a separate collaborative project, a lectin called SIGLEC-8 was discovered on human eosinophils, basophils, and mast cells - the cells that drive allergic inflammation including asthma. Engaging Siglec-8 on the surface of these cells inhibits allergic inflammation. We identified a glycan structure that binds to Siglec-8 and that represents a potential lead compound for glycan-based asthma therapy. The study of Siglecs as regulators of inflammation may provide therapeutic opportunities to reduce the severity of asthma and other lung inflammatory diseases.
- Kiwamoto T, Brummet ME, Wu F, Motari MG, Smith DF, Schnaar RL, Zhu Z, Bochner BS. 2013. Mice deficient in the St3gal3 gene product alpha2,3 sialyltransferase (ST3Gal-III) exhibit enhanced allergic eosinophilic airway inflammation. J Allergy Clin Immunol. In press (Epub ahead of print). Pub Med Reference
- Mountney A, Zahner MR, Sturgill ER, Riley CJ, Aston JW, Oudega M, Schramm LP, Hurtado A, Schnaar RL. 2013. Sialidase, chondroitinase ABC, and combination therapy after spinal cord contusion injury. J Neurotrauma. 30:181-190. Pub Med Reference
- Sturgill ER, Aoki K, Lopez PH, Colacurcio D, Vajn K, Lorenzini I, Majic S, Yang WH, Heffer M, Tiemeyer M, Marth JD, Schnaar RL. 2012. Biosynthesis of the major brain gangliosides GD1a and GT1b. Glycobiology. 22:1289-1301. Pub Med Reference
- Essaka DC, Prendergast J, Keithley RB, Hindsgaul O, Palcic MM, Schnaar RL, Dovichi NJ. 2012. Single cell ganglioside catabolism in primary cerebellar neurons and glia. Neurochem Res. 37:1308-1314. Pub Med Reference
- Lopez PH, Ahmad AS, Mehta NR, Toner M, Rowland EA, Zhang J, Dore S, Schnaar RL. 2011. Myelin-associated glycoprotein protects neurons from excitotoxicity. J Neurochem. 116:900-908. Pub Med Reference
- Mountney A, Zahner MR, Lorenzini I, Odega M, Schramm LP, Schnaar RL. 2010. Sialidase enhances recovery from spinal cord contusion injury. Proc. Natl. Acad. Sci. USA 107:11561-6. Pub Med Reference
- Mehta NR, Nguyen T, Bullen JW Jr, Griffin JW, Schnaar RL. 2010. Myelin-associated glycoprotein (MAG) protects neurons from acute toxicity using a ganglioside-dependent mechanism. ACS Chem. Neurosci. 1:215-222. Pub Med Reference
- Lopez PH, Schnaar RL. 2009. Gangliosides in cell recognition and membrane protein regulation. Curr. Opin. Struct. Biol. 19 2009 July 14:[Epub ahead of print]. Pub Med Reference
- Hudson SA, Bovin N, Schnaar RL, Crocker PR, Bochner BS. 2009. Eosinophil-selective binding and proapoptotic effect in vitro of a synthetic Siglec-8 ligand, polymeric 6'-sulfated sialyl Lewis X. J. Pharmacol. Exp. Ther. 330:608-612. Pub Med Reference
- Nguyen T, Mehta NR, Conant K, Kim K, Jones M, Calabresi PA, Melli G, Hoke A, Schnaar RL, Ming GL, Song H, Keswani SC, Griffin JW. 2009. Axonal protective effects of the myelin associated glycoprotein. J. Neurosci. 29:630-637. Pub Med Reference
Other graduate programs in which Dr. Schnaar participates: