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Jamey Marth

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Jamey Marth
NationalityAmerican
Alma materUniversity of Washington
Scientific career
FieldsMolecular biology
Cellular biology
InstitutionsSBP Medical Discovery Institute
UC Santa Barbara
Howard Hughes Medical Institute
UC San Diego
Doctoral advisorEdwin G. Krebs, Roger M. Perlmutter

Jamey Marth, Ph.D., is a molecular and cellular biologist. He is currently on the faculty of the University of California, Santa Barbara (UCSB) and the SBP Medical Discovery Institute of La Jolla, California. At UCSB, Dr. Marth is the Director of the Center for Nanomedicine and a Professor in the Department of Molecular, Cellular and Developmental Biology.[1][2] He is also the inaugural recipient of the John Carbon Endowed Chair of Biochemistry and Molecular Biology and the recipient of the Duncan and Suzanne Mellichamp Endowed Chair of Systems Biology.[3]

His research has largely focused on molecular cell biology and, in particular, how protein glycosylation contributes to the mechanisms of health and common diseases including diabetes, sepsis, inflammatory diseases, and autoimmunity.[4] His research has identified metabolic causes of common diseases, and is credited with the conception and co-development of Cre-Lox recombination as a form of conditional mutagenesis in living mammals.[5]

Education

Marth earned a Ph.D. in Pharmacology from the University of Washington in 1987.[citation needed] During his time at Washington as a graduate student, he was mentored by Roger M. Perlmutter and Edwin G. Krebs.[citation needed] Marth was Perlmutter's first graduate student.[6][7] Marth's first faculty position after earning his doctorate was at the University of British Columbia's Biomedical Research Centre in Vancouver, British Columbia, Canada.[8][9]

Career

While in Vancouver, Marth conceived and co-developed Cre-Lox recombination for conditional mutagenesis. This technology has enabled the study of gene function in specific cell types and at specific times among living animals.[10][11] 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.[8] His research at HHMI and UCSD helped bolster an already renowned glycobiology program that originated with Ajit Varki and later included Jeffrey Esko.[12]

In 2009, he accepted a position at the University of California, Santa Barbara and the Sanford-Burnham Medical Research Institute as the Director of the Center for Nanomedicine. He also became the inaugural recipient of the John Carbon Endowed Chair in Biochemistry and Molecular Biology and the recipient of the Duncan and Suzanne Mellichamp Endowed Chair of Systems Biology.[3][8]

Research

Marth’s research has included the development of new methodologies and conceptual advances in the understanding of disease. His conception and co-development of Cre-Lox conditional mutagenesis has provided a means to discover the mechanistic underpinnings of development and disease, and continues to be used by scientists worldwide.[13] Prior to the development of conditional mutagenesis, the use of homologous recombination was limited to systemic gene targeting and mutation.[5] 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 in how common diseases originate in the absence of discernible pathogenic genetic variation.[14] Marth has further used Cre-Lox conditional mutagenesis to establish a reproducible method for obtaining animal models of essential X chromosome-linked genes.[15] These studies further explained how glycan linkages function in the origins of disease at the metabolic and cellular levels.[16][17][18]

Marth's early studies of glycosylation and glycan linkages revealed a profound effect on immunity and contributed to the genesis of the related field of glycoimmunology.[16] Marth's lab further discovered relationships between aberrant glycan linkages and autoimmune diseases including the fact that alterations of glycan linkages could initiate chronic inflammation in the development of autoimmunity.[19] Marth's research has shown that the occurrence of autoimmune conditions (such as lupus) in mammals can be caused by the presence of abnormal glycan structures within the body.[20]

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 has in the origin of the disease. Their research showed that the malfunction of pancreatic beta cells was the major contributor to disease onset. Their research indicated that genetic variation was unlikely to be the cause of obesity-associated type 2 diabetes in humans. Instead, their models suggested that metabolic alterations of pancreatic beta cells due to an elevation of fatty acids in obesity disabled glucose sensing, resulting in hyperglycemia with glucose intolerance. Marth’s laboratory further found that this pathway was induced in human patients with type 2 diabetes and was responsible for a significant amount of insulin resistance present in obesity-associated diabetes.[2][4][21]

The pathological features of 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. Their studies revealed both a biological purpose of the receptor and how to use it for therapeutic purposes in pneumococcal sepsis.[3]

In 2008, Dr. Marth published an enumeration of the building blocks of life, all of which fall under the 4 types of macromolecules present in all cells (glycans, lipids, nucleic acids, and proteins).[22] This concept is becoming a feature of modern cell biology texts.[23] Marth and other colleagues have called attention to the fact that only half of these macromolecules are encoded in the genome, suggesting that a more holistic and rigorous approach is needed to understanding cell biology and the origins of disease.[24]

In his position as the Director of the Center of Nanomedicine, Marth and his team are exploring the application of new delivery methods to directly visualize and treat disease in collaboration with Center for Nanomedicine Co-Founder, Dr. Erkki Ruoslahti.[25][26]

Selected publications

  • Grewal, P.K.; Aziz, P.Z.; Uchiyama, S.; Rubio, G.R.; Lardone, R.D.; Le, D.; Varki, N.; Nizet, V.; Marth, J.D. (2013). "Inducing host protection in pneumococcal sepsis by preactivation of the Ashwell-Morell receptor". Proc. Natl. Acad. Sci. USA. 110: 20218–20223. doi:10.1073/pnas.1313905110. PMC 3864324. PMID 24284176.
  • Ohtsubo, K.; Chen, M. Z.; Olefsky, J.M.; Marth, J.D. (2011). "Pathway to diabetes through attenuation of pancreatic beta cell glycosylation and glucose transport". Nat. Med. 17: 1067–1075. doi:10.1038/nm.2414. PMC 3888087.
  • Grewal, P.K.; Uchiyama, S.; Ditto, D.; Varki, N.; Le, D.T.; Nizet, V.; Marth, J.D. (2008). "The Ashwell receptor mitigates the lethal coagulopathy of sepsis". Nat. Med. 14: 648–655. doi:10.1038/nm1760. PMC 2853759. PMID 18488037.
  • Marth, J.D. (2008). "A unified vision of the building blocks of life". Nat. Cell Biol. 10: 1015–1016. doi:10.1038/ncb0908-1015. PMC 2892900. PMID 18758488.
  • Marth, J.D.; Grewal, P.K. (2008). "Mammalian glycosylation in immunity". Nat. Rev. Immunol. 8: 874–887. doi:10.1038/nri2417. PMC 2768770.
  • Green, R.S.; Stone, E.L. Tenno; Lehtonen, E.; Farquhar, M.G.; Marth, J.D. (2007). "Mammalian N-glycan branching protects against innate immune self-recognition and inflammation in autoimmune disease pathogenesis". Immunity. 27: 308–320. doi:10.1016/j.immuni.2007.06.008. PMID 17681821.
  • Ohtsubo, K.; Marth, J.D. (2006). "Glycosylation in cellular mechanisms of health and disease". Cell. 126: 855–867. doi:10.1016/j.cell.2006.08.019.
  • Ohtsubo, K., and Marth, J.D. (2006). Conditional mutagenesis of the genome using site-specific DNA recombination. In: Gene Transfer: Delivery and Expression of DNA and RNA, A laboratory Manual (Friedman and Rossi; eds) Cold Spring Harbor Press, N.Y., pp. 587–602.
  • Grewal, P.K.; Boton, M.; Rameriz, K.; Collins, B.E.; Saito, A.; Green, R.S.; Ohtsubo, K.; Chui, D.; Marth, J.D. (2006). "ST6Gal-I restrains CD22-dependent antigen receptor endocytosis and Shp-1 recruitment in normal and pathogenic immune signaling". Mol. Cell. Biol. 26: 4970–4981. doi:10.1128/mcb.00308-06. PMC 1489171.
  • Ohtsubo, K.; Takamatsu, S.; Minowa, M.T.; Yoshida, A.; Takeuchi, M.; Marth, J.D. (2005). "Dietary and genetic control of glucose transporter-2 glycosylation promotes insulin secretion in suppressing diabetes". Cell. 123: 1307–1321. doi:10.1016/j.cell.2005.09.041. PMID 16377570.
  • Chui, D.; Sellakumar, G.; Green, R.; Sutton-Smith, M.; McQuistan, T.; Marek, K.; Morris, H.; Dell, A.; Marth, J.D. (2001). "Genetic remodeling of protein glycosylation in vivo induces autoimmune disease". Proc Natl Acad Sci USA. 98: 1142–1147. doi:10.1073/pnas.98.3.1142. PMC 14722. PMID 11158608.
  • Chui, D.; Oh-Eda, M.; Liao, Y.F.; Panneerselvam, K.; Lal, A.; Marek, K.W.; Freeze, H.H.; Moremen, K.W.; Fukuda, M.N.; Marth, J.D. (1997). "Alpha-mannosidase-II deficiency results in dyserythropoiesis and unveils an alternate pathway in oligosaccharide biosynthesis". Cell. 90: 157–67. doi:10.1016/s0092-8674(00)80322-0.

References

  1. ^ Hardy, Quentin (11 July 2011). "Big Data's People-Changing Machine". Forbes. Retrieved 29 April 2015. {{cite news}}: Italic or bold markup not allowed in: |publisher= (help)
  2. ^ a b Foulsham, George (16 August 2011). "Fatty diet triggers diabetes onslaught". Futurity. Retrieved 12 March 2015.
  3. ^ a b c "Biomedical scientist discovers method to increase survival in sepsis". Science Daily. 25 November 2013. Retrieved 12 March 2015.
  4. ^ a b "Pioneering research on type 2 diabetes". University of California. 4 January 2013. Retrieved 12 March 2015.
  5. ^ a b Wadman, Meredith (27 August 1998). "DuPont opens up access to genetics tool" (PDF). Nature. 394 (819). doi:10.1038/29607. PMID 9732857. Retrieved 12 March 2015.
  6. ^ "Jamey Marth". www.mcdb.uscb.com. University of California, Santa Barbara. Retrieved 12 March 2015.
  7. ^ "The American Association of Immunologists Oral History Project" (PDF). American Association of Immunologists. 23 January 2013. Retrieved 12 March 2015.
  8. ^ a b c "Cellular and Molecular Medicine - 2009 Annual Report" (PDF). University of California, San Diego. 2009. Retrieved 12 March 2015.
  9. ^ Richards, James D.; Gold, Michael R.; Hourihane, Sharon L.; DeFranco, Anthony L.; Matsuuchi, Linda (15 March 1996). "Reconstitution of B Cell Antigen Receptor-induced Signaling Events in a Nonlymphoid Cell Line by Expressing the Syk Protein-tyrosine Kinase". Journal of Biological Chemistry. 271: 6458–6466. doi:10.1074/jbc.271.11.6458. Retrieved 12 March 2015.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  10. ^ Gu, H; Marth, JD; Orban, PC; Mossmann, H; Rajewsky, K (1 July 1994). "Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting". Science. 265: 103–6. doi:10.1126/science.8016642. PMID 8016642.
  11. ^ Orban, PC; Chui, D; Marth, JD (1992). "Tissue-and site-specific DNA recombination in transgenic mice". Proc. Natl. Acad. Sci. USA. 89: 6861–6865. doi:10.1073/pnas.89.15.6861. PMC 49604. PMID 1495975.
  12. ^ "GRTC". aiHit Limited. Retrieved 12 March 2015.
  13. ^ Saure, B. (2002). "Cre/lox: one more step in the taming of the genome". Endocrine. 19: 221–8. doi:10.1385/endo:19:3:221. PMID 12624421.
  14. ^ Hennet, T.; Hagen, F.K.; Tabak, L.A.; Marth, J.D. (1995). "T cell-specific deletion of a polypeptide N-acetylgalactosaminyltransferase gene by site-directed recombination". Proc. Natl. Acad. Sci. USA. 92 (26): 12070–4. doi:10.1073/pnas.92.26.12070. PMC 40298. PMID 8618846.
  15. ^ Shafi, R; Iver, SP; Ellies, LG; O'Donnell, N; Marek, KW; Chui, D; Hart, GW; Marth, JD (23 May 2000). "The O-GlcNAc transferase gene resides on the X chromosome and is essential for embryonic stem cell viability and mouse ontogeny". Proc Natl Acad Sci USA. 97: 5735–9. doi:10.1073/pnas.100471497. PMC 18502. PMID 10801981.
  16. ^ a b Borman, Stu (30 July 2007). "Sugar Medicine". Chemical and Engineering News. Retrieved 12 March 2015.
  17. ^ Ellies, L.G.; Tsuboi, S.; Petryniak, B.; Lowe, J.B.; Fukuda, M.; Marth, J.D. (1998). "Core 2 O-glycan biosynthesis distinguishes between selectin ligands essential for leukocyte homing and inflammation". Immunity. 9 (6): 881–90. doi:10.1016/s1074-7613(00)80653-6. PMID 9881978.
  18. ^ Edelson, Stephen B.; Deborah Mitchell (2003). What Your Doctor May Not Tell You About(TM): Autoimmune Disorders: The Revolutionary Drug-free Treatments for Thyroid Disease, Lupus, MS, IBD, Chronic. Grand Central Publishing. ISBN 0446679240.
  19. ^ Chui, Daniel; et al. (30 January 2001). "Genetic remodeling of protein glycosylation in vivo induces autoimmune disease". Proc Natl Acad Sci USA. 98: 1142. doi:10.1073/pnas.98.3.1142. PMC 14722. PMID 11158608.
  20. ^ Green, R.S.; et al. (27 August 2007). "Mammalian N-glycan branching protects against innate immune self-recognition and inflammation in autoimmune disease pathogenesis". Immunity. 27: 308–20. doi:10.1016/j.immuni.2007.06.008. PMID 17681821.
  21. ^ Gallagher, James (14 August 2011). "Fat 'disrupts sugar sensors causing type 2 diabetes'". BBC. Retrieved 12 March 2015.
  22. ^ Kain, Debra (3 September 2008). "Do 68 Molecules Hold the Key to Understanding Disease?". UC San Diego News Center. Retrieved 29 April 2015.
  23. ^ Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keither; Walter, Peter (2002). Molecular Biology of the Cell (5th ed.). Garland Science. ISBN 0815332181.
  24. ^ Piquepaille, Roland (8 September 2008). "68 molecular building blocks of life". ZDNet. Retrieved 29 April 2015.
  25. ^ Zeller, Jeremy (10 January 2011). "UCSB's Center for Nanomedicine Plants Seeds of Economic Development in Goleta Valley". Noozhawk. Retrieved 12 March 2015.
  26. ^ "Envisioning Novel Approaches for Eye Disease: 'The New Medicine' at UCSB". Noozhawk. 16 October 2012. Retrieved 29 April 2015.
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