Jamey Marth, Ph.D.

I am a molecular and cellular biologist specializing in diseases attributable to protein glycosylation. My education and training span molecular genetics, biochemistry, pharmacology, cell biology, immunology, hematology, developmental biology, microbiology, and glycobiology.  

As an enzymatic process essential to cells, glycosylation produces saccharides linked by glycosidic bonds to proteins, lipids, and themselves, termed glycans. The vast majority of secreted and cell surface proteins are post-translationally modified by glycosylation during transit through the secretory pathway, termed glycoproteins. A widely used college level cell biology textbook authored by others includes glycans as one of the four main families of the organic molecules of all cells, with lipids, proteins, and nucleic acids and that together they compose the macromolecules and other assemblies of the cell. The structures of glycans (and lipids) are, however, synthesized by template-independent processes, rendering them hard to predict and study. Cells produce and regulate an abundant and diverse glycome of glycosidic linkages in which some of the biological information is decoded by one or more glycan-binding receptors, termed lectins.

Glycans and lectins represent a significant percentage of genes in the genomes of organisms, with several hundred present in mammals. Because glycan biosynthesis, diversification, and degradation rely upon corresponding gene and enzyme function, glycan function can be investigated similarly to other enzymatic and metabolic pathways, such protein phosphorylation. However, we and others found that intact organisms were typically required to discover the functions of protein glycosylation in mammals. My laboratory has focused on discovering the biological information contained within select glycosidic linkages of N- and O-glycans in determining the function and fate of discrete glycoproteins that further contribute to the pathogenesis of autoimmune disease, colitis, diabetes, and sepsis.

To understand the nature and extent of the information generated by glycosidic linkages, we have applied multiple molecular approaches to investigate protein glycosylation in mice and humans. In doing so, we have contributed to the development of enabling technologies with broad applicability, such as conditional mutagenesis by Cre-lox recombination in living animals to determine gene function with temporal and spatial selectivity. My laboratory also develops and studies experimental systems that may better represent real-world models of environmental factors that trigger acquired and common human diseases, results from which have been consistent with clinical findings of human patients. My laboratory includes interdisciplinary team-based collaborations that integrate expertise in immunology, infectious disease, hematology, and more recently, cancer, and is especially focused upon glycosidic linkages attached to the N- and O-glycans of glycoproteins.

The physiological systems regulated by protein glycosylation are broad even when comparing among sequential biosynthetic steps, and our findings continue to indicate the presence of undiscovered information of medical relevance residing in the glycan linkages of glycoproteins.