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Jamey Marth

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Jamey Marth
BornSarasota, Florida
NationalityAmerican and Canadian
Alma materUniversity of Washington
Scientific career
FieldsMolecular biology
Cellular biology
Inflammatory diseases
Immunology
Glycobiology
InstitutionsSBP Medical Discovery Institute
UC Santa Barbara
Howard Hughes Medical Institute
UC San Diego
Doctoral advisorsRoger M. Perlmutter and Edwin G. Krebs

Jamey Marth is a molecular and cellular biologist. He is currently on the faculty of the SBP Medical Discovery Institute in La Jolla, California where he is Director of the Immunity and Pathogenesis program.

His research has largely focused on how protein glycosylation contributes to the origins of common diseases and syndromes including diabetes, sepsis, colitis, and autoimmunity.

Education

Marth earned a Ph.D. in Pharmacology from the University of Washington in 1987. During his time at Washington as a graduate student, he was mentored by Roger M. Perlmutter and Edwin G. Krebs. Marth was Perlmutter's first graduate student.

Career

Following his time as a staff scientist at Oncogen Corporation in Seattle, Marth was recruited to the founding faculty of the Biomedical Research Centre in Vancouver, British Columbia, Canada, where he was also appointed as a professor in the Department of Medical Genetics at the University of British Columbia. In 1995, George Palade and Marilyn Farquhar (among others) recruited Marth to the University of California, San Diego (UCSD) in the Department of Cellular and Molecular Medicine. Upon his arrival, he was appointed as an Investigator of the Howard Hughes Medical Institute. Marth spent more than 14 years in this position at UCSD. His research at HHMI and UCSD helped bolster an already renowned glycobiology program that originated with Ajit Varki and later included Jeffrey Esko.

In 2009, he accepted a position at the University of California, Santa Barbara (UCSB) and the Sanford-Burnham Medical Research Institute as the Director of the Center for Nanomedicine. He also then became the inaugural recipient of the Carbon Chair in Biochemistry and Molecular Biology and the recipient of the Mellichamp Chair of Systems Biology.

Research

Marth's research is credited with the development of methodologies applicable to investigating the origins of disease. His conception and co-development of Cre-Lox conditional mutagenesis has provided a means to further perceive the mechanistic underpinnings of disease, and continues to be used by scientists worldwide. Prior to the development of conditional mutagenesis, the use of homologous recombination was limited to systemic gene targeting and mutation. Marth's use of Cre-Lox conditional mutagenesis established the presence and functions of multiple and in some cases previously unknown enzymes participating in protein glycosylation, an area of research that has become a focus of exploration of the genetic and metabolic origins of disease. Marth also used Cre-Lox mutagenesis to establish a reproducible method for obtaining animal models of essential X chromosome-linked genes.

Marth's early studies of glycosylation and glycan linkages revealed a profound effect on immunity and contributed to the genesis of the related sub-field termed glycoimmunology. Marth's laboratory discovered connections between aberrant glycan linkages and autoimmune diseases including the fact that the exposure of cryptic immature glycan linkages in mammals could initiate chronic sterile inflammation leading to the development of autoimmunity. Those findings indicated that autoimmunity can be precipitated by the presence of abnormal glycan structures within the body.

Marth's laboratory has also taken a close look at the molecular and cellular bases of Type 2 diabetes and the role that protein glycosylation plays in the origin of the disease. Their research demonstrated that acquired pancreatic beta cell dysfunction was the major contributor of disease onset and corroborated views that genetic variation was unlikely to be the primary cause of obesity-associated Type 2 diabetes in humans. Instead, their findings revealed that altered pancreatic beta cell glycosylation resulting from elevated fatty acid levels in obesity disabled glucose sensing, resulting in hyperglycemia with glucose intolerance. Marth's research team further found that this pathway was induced in human patients with Type 2 diabetes and was responsible for a significant amount of the insulin resistance present in experimentally-induced obesity-associated diabetes.

The pathological underpinnings of inflammatory diseases including sepsis have also been the subject of research by Marth's laboratory. Marth and colleagues discovered the first physiological purpose of the Ashwell-Morell Receptor (AMR), a hepatocyte lectin discovered by Gilbert Ashwell and Anatol Morell. Marth's studies revealed the presence of an intrinsic mechanism of secreted protein aging and turnover first proposed by Ashwell and Morell in the 1960s, and which participates in controlling the half-lives and functions of secreted and cell surface glycoproteins. Their studies further identified how AMR function can be modulated for therapeutic purposes.

In 2008, Marth published an initial enumeration of the building blocks of life, all of which fall under the four types of cellular macromolecules (glycans, lipids, nucleic acids, and proteins). This accounting has become an educational feature of cell biology texts. Marth and other colleagues have called attention to the fact that only half of these macromolecules are encoded by the genome, suggesting that a more holistic approach is needed in biomedical research to fully understand and intervene in the origins and progression of disease.

Selected publications

References

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  2. ^ "Fatty diet triggers diabetes onslaught". Futurity. 2011-08-16. Retrieved 2021-07-14.
  3. ^ "Biomedical scientist discovers method to increase survival in sepsis". ScienceDaily. Retrieved 2021-07-14.
  4. Marth, Jamey David (2020). "Glycosylation in a Common Mechanism of Colitis and Sepsis". The FASEB Journal. 34 (S1): 1. doi:10.1096/fasebj.2020.34.s1.00176. ISSN 1530-6860. S2CID 218775798.
  5. ^ "Jamey Marth Honored for Research Linking Glycans to Diabetes, Lupus, Sepsis". www.newswise.com. Retrieved 2021-07-14.
  6. ^ "Jamey Marth - MCDB - UC Santa Barbara". 2021-04-18. Archived from the original on 2021-04-18. Retrieved 2021-07-14.
  7. "Notable Members" (PDF). 2016-01-02. Archived from the original (PDF) on 2016-01-02. Retrieved 2021-07-14.
  8. Haltiwanger, Robert S. (2000-12-01). "Essentials of Glycobiology. Ajit Varki , Richard Cummings , Jeffrey Esko , Hudson Freeze , Gerald Hart , Jamey Marth , Maarten Chrispeels , Ole Hindsgaul , James C. Paulson , John Lowe , Adriana Manzi , Leland Powell , Herman van Halbeek". The Quarterly Review of Biology. 75 (4): 451–452. doi:10.1086/393647. ISSN 0033-5770.
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  11. "Floxed Mice - Cre-lox Recombination and Gene Targeting". www.genetargeting.com. 12 June 2019. Retrieved 2021-07-14.
  12. Marth, J. D. (1996-05-01). "Recent advances in gene mutagenesis by site-directed recombination". The Journal of Clinical Investigation. 97 (9): 1999–2002. doi:10.1172/JCI118634. PMC 507272. PMID 8621787. Retrieved 2021-07-14.
  13. Orban, P. C.; Chui, D.; Marth, J. D. (1992-08-01). "Tissue- and site-specific DNA recombination in transgenic mice". Proceedings of the National Academy of Sciences of the United States of America. 89 (15): 6861–6865. Bibcode:1992PNAS...89.6861O. doi:10.1073/pnas.89.15.6861. ISSN 0027-8424. PMC 49604. PMID 1495975.
  14. Gu, H.; Marth, J. D.; Orban, P. C.; Mossmann, H.; Rajewsky, K. (1994-07-01). "Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting". Science. 265 (5168): 103–106. Bibcode:1994Sci...265..103G. doi:10.1126/science.8016642. ISSN 0036-8075. PMID 8016642.
  15. Hennet, T.; Hagen, F. K.; Tabak, L. A.; Marth, J. D. (1995-12-19). "T-cell-specific deletion of a polypeptide N-acetylgalactosaminyl-transferase gene by site-directed recombination". Proceedings of the National Academy of Sciences of the United States of America. 92 (26): 12070–12074. Bibcode:1995PNAS...9212070H. doi:10.1073/pnas.92.26.12070. ISSN 0027-8424. PMC 40298. PMID 8618846.
  16. Wadman, M. (1998-08-27). "DuPont opens up access to genetics tool". Nature. 394 (6696): 819. Bibcode:1998Natur.394..819W. doi:10.1038/29607. ISSN 0028-0836. PMID 9732857. S2CID 4431441.
  17. ^ News, Chemical & Engineering. "Chemical & Engineering News: Cover Story - Sugar Medicine". pubsapp.acs.org. Retrieved 2021-07-14. {{cite web}}: |last= has generic name (help)
  18. ^ Ohtsubo, Kazuaki; Marth, Jamey D. (2006-09-08). "Glycosylation in Cellular Mechanisms of Health and Disease". Cell. 126 (5): 855–867. doi:10.1016/j.cell.2006.08.019. ISSN 0092-8674. PMID 16959566. S2CID 9474696.
  19. Shafi, Raheel; Iyer, Sai Prasad N.; Ellies, Lesley G.; O'Donnell, Niall; Marek, Kurt W.; Chui, Daniel; Hart, Gerald W.; Marth, Jamey D. (2000-05-23). "The O-GlcNAc transferase gene resides on the X chromosome and is essential for embryonic stem cell viability and mouse ontogeny". Proceedings of the National Academy of Sciences of the United States of America. 97 (11): 5735–5739. Bibcode:2000PNAS...97.5735S. doi:10.1073/pnas.100471497. ISSN 0027-8424. PMC 18502. PMID 10801981.
  20. ^ Marth, Jamey D.; Grewal, Prabhjit K. (2008). "Mammalian glycosylation in immunity". Nature Reviews Immunology. 8 (11): 874–887. doi:10.1038/nri2417. ISSN 1474-1741. PMC 2768770. PMID 18846099.
  21. Baum, Linda G.; Crocker, Paul R. (2009). "Glycoimmunology: ignore at your peril". Immunological Reviews. 230 (1): 5–8. doi:10.1111/j.1600-065X.2009.00800.x. ISSN 1600-065X. PMID 19594625. S2CID 38067762.
  22. Green, Ryan S.; Stone, Erica L.; Tenno, Mari; Lehtonen, Eero; Farquhar, Marilyn G.; Marth, Jamey D. (2007-08-01). "Mammalian N-glycan branching protects against innate immune self-recognition and inflammation in autoimmune disease pathogenesis". Immunity. 27 (2): 308–320. doi:10.1016/j.immuni.2007.06.008. ISSN 1074-7613. PMID 17681821.
  23. ^ Ohtsubo, Kazuaki; Chen, Mark Z; Olefsky, Jerrold M; Marth, Jamey D (2011-08-14). "Pathway to diabetes through attenuation of pancreatic beta cell glycosylation and glucose transport". Nature Medicine. 17 (9): 1067–1075. doi:10.1038/nm.2414. ISSN 1078-8956. PMC 3888087. PMID 21841783.
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  28. Yang, Won Ho; Heithoff, Douglas M.; Aziz, Peter V.; Sperandio, Markus; Nizet, Victor; Mahan, Michael J.; Marth, Jamey D. (2017-12-22). "Recurrent Infection Progressively Disables Host Protection Against Intestinal Inflammation". Science. 358 (6370): eaao5610. doi:10.1126/science.aao5610. ISSN 0036-8075. PMC 5824721. PMID 29269445.
  29. Grewal, Prabhjit K; Uchiyama, Satoshi; Ditto, David; Varki, Nissi; Le, Dzung T; Nizet, Victor; Marth, Jamey D (2008). "The Ashwell receptor mitigates the lethal coagulopathy of sepsis". Nature Medicine. 14 (6): 648–655. doi:10.1038/nm1760. ISSN 1078-8956. PMC 2853759. PMID 18488037.
  30. Yang, Won Ho; Aziz, Peter V.; Heithoff, Douglas M.; Mahan, Michael J.; Smith, Jeffrey W.; Marth, Jamey D. (2015-11-03). "An intrinsic mechanism of secreted protein aging and turnover". Proceedings of the National Academy of Sciences of the United States of America. 112 (44): 13657–13662. Bibcode:2015PNAS..11213657Y. doi:10.1073/pnas.1515464112. ISSN 1091-6490. PMC 4640737. PMID 26489654.
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