Jamey Marth, Ph.D.

Jamey Marth's Research Focus

Inflammatory/Autoimmune Disease, Diabetes - General, Sepsis, Cancer, Colitis

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.

 

Education

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


TMC Accessory

Publications

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

Recurrent infection progressively disables host protection against intestinal inflammation.

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

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CCR3-dependent eosinophil recruitment is regulated by sialyltransferase ST3Gal-IV.

Immler R, Nussbaumer K, Doerner A, El Bounkari O, Huber S, Abisch J, Napoli M, Schmidt S, Margraf A, Pruenster M, Rohwedder I, Lange-Sperandio B, Mall MA, de Jong R, Ohnmacht C, Bernhagen J, Voehringer D, Marth JD, Frommhold D, Sperandio M

Proc Natl Acad Sci U S A 2024 May 7 ;121(19):e2319057121

Innate mechanism of mucosal barrier erosion in the pathogenesis of acquired colitis.

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

Establishment of blood glycosidase activities and their excursions in sepsis.

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

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