Jamey Marth

Marth earned a Ph.D. in Pharmacology from the University of Washington in 1987.[6] 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.[7][8] 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.[9][10]

While in Vancouver, Marth and colleagues conceived and 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.[11][12] 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.[9] His research at HHMI and UCSD helped bolster an already renowned glycobiology program that originated with Ajit Varki and later included Jeffrey Esko.[13]

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 then became the inaugural recipient of the Carbon Chair in Biochemistry and Molecular Biology and the recipient of the Mellichamp Chair of Systems Biology.[3][9] In his position as the Director of the Center of Nanomedicine, Marth and his team further explored the application of new delivery methods to directly visualize and treat disease, initially in collaboration with Center for Nanomedicine Co-Founder, Dr. Erkki Ruoslahti.[14][15]

Marth’s research is credited with the development of new methodologies and conceptual advances in understanding the origins of disease. His conception and co-development of Cre-Lox conditional mutagenesis has provided a means to further discover the mechanistic underpinnings of development and disease, and continues to be used by scientists worldwide.[16] 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.[17] Marth has further used Cre-Lox conditional mutagenesis to establish a reproducible method for obtaining animal models of essential X chromosome-linked genes.[18] These studies further explained how glycan linkages contribute to the origins of disease at the metabolic and cellular levels.[19][20][21]

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.[19] Marth's lab further discovered relationships 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.[22] 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.[23]

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][24]

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).[25] This concept is becoming a feature of modern cell biology texts.[26] 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 fully understand cell biology and the origins of disease.[27]

• 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 (50): 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 (9): 1067–1075. doi:10.1038/nm.2414. PMC 3888087. PMID 21841783.
• 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 (6): 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 (9): 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 (11): 874–887. doi:10.1038/nri2417. PMC 2768770. PMID 18846099.
• 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 (2): 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 (5): 855–867. doi:10.1016/j.cell.2006.08.019. PMID 16959566. S2CID 9474696.
• 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 (13): 4970–4981. doi:10.1128/mcb.00308-06. PMC 1489171. PMID 16782884.
• 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 (7): 1307–1321. doi:10.1016/j.cell.2005.09.041. PMID 16377570. S2CID 14509553.
• 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 (3): 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 (1): 157–67. doi:10.1016/s0092-8674(00)80322-0. PMID 9230311. S2CID 6064567.