Jamey Marth's Research Focus
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.
Jamey Marth's Bio
Jamey Marth is a Professor at Sanford Burnham Prebys. He has also been Director of the Center for Nanomedicine at the University of California Santa Barbara and Professor in the Department of Molecular, Cellular, and Developmental Biology. Dr. Marth received a Ph.D. degree in Pharmacology from the University of Washington where he trained in the laboratories of Roger M. Perlmutter and Edwin G. Krebs. Dr. Marth’s previous positions included Professor of Medical Genetics at the Biomedical Research Center, University of British Columbia; Professor of Cellular and Molecular Medicine at the University of California San Diego; and Investigator of the Howard Hughes Medical Institute.
1987: Ph.D., University of Washington, Pharmacology
1984: B.S., University of Oregon, Genetics and Chemistry
Honors and Recognition
2017: Karl Meyer Award, Society for Glycobiology
2009-2020: John Carbon Chair in Biochemistry and Molecular Biology
2009-2019: Duncan and Suzanne Mellichamp Chair in Systems Biology
2009: Julius Stone Lectureship Award: Society for Investigative Dermatology
1995-2009: Investigator Award, Howard Hughes Medical Institute
1991-1995: Faculty Scholarship, The Medical Research Council of Canada
Pathway to diabetes through attenuation of pancreatic beta cell glycosylation and glucose transport.
Ohtsubo K, Chen MZ, Olefsky JM, Marth JD
Nat Med 2011 Aug 14 ;17(9):1067-75
Yang WH, Heithoff DM, Aziz PV, Sperandio M, Nizet V, Mahan MJ, Marth JD
Science 2017 Dec 22 ;358(6370)
Accelerated Aging and Clearance of Host Anti-inflammatory Enzymes by Discrete Pathogens Fuels Sepsis.
Yang WH, Heithoff DM, Aziz PV, Haslund-Gourley B, Westman JS, Narisawa S, Pinkerton AB, Millán JL, Nizet V, Mahan MJ, Marth JD
Cell Host Microbe 2018 Oct 10 ;24(4):500-513.e5
Yang WH, Aziz PV, Heithoff DM, Kim Y, Ko JY, Cho JW, Mahan MJ, Sperandio M, Marth JD
iScience 2023 Oct 20 ;26(10):107883
Cataloging natural sialic acids and other nonulosonic acids (NulOs), and their representation using the Symbol Nomenclature for Glycans.
Lewis AL, Toukach P, Bolton E, Chen X, Frank M, Lütteke T, Knirel Y, Schoenhofen I, Varki A, Vinogradov E, Woods RJ, Zachara N, Zhang J, Kamerling JP, Neelamegham S, SNFG Discussion Group
Glycobiology 2023 Mar 6 ;33(2):99-103
Haslund-Gourley BS, Aziz PV, Heithoff DM, Restagno D, Fried JC, Ilse MB, Bäumges H, Mahan MJ, Lübke T, Marth JD
PNAS Nexus 2022 Jul ;1(3):pgac113
Glycomic Analysis Reveals a Conserved Response to Bacterial Sepsis Induced by Different Bacterial Pathogens.
Heindel DW, Chen S, Aziz PV, Chung JY, Marth JD, Mahal LK
ACS Infect Dis 2022 May 13 ;8(5):1075-1085
Coagulation factor protein abundance in the pre-septic state predicts coagulopathic activities that arise during late-stage murine sepsis.
Heithoff DM, Pimienta G, Mahan SP, Yang WH, Le DT, House JK, Marth JD, Smith JW, Mahan MJ
EBioMedicine 2022 Apr ;78:103965
Neu3 neuraminidase induction triggers intestinal inflammation and colitis in a model of recurrent human food-poisoning.
Yang WH, Westman JS, Heithoff DM, Sperandio M, Cho JW, Mahan MJ, Marth JD
Proc Natl Acad Sci U S A 2021 Jul 20 ;118(29)