The 2017 Karl Meyer Award goes to Jamey Marth

Donald L. Jarvis¹
Secretary, Society for Glycobiology, Department of Molecular Biology, University of Wyoming, Laramie, WY 82071 USA

The Society for Glycobiology is pleased to announce Dr. Jamey Marth as the recipient of the 2017 Karl Meyer Lectureship Award². The Karl Meyer Award was established in 1990 to honor the distinguished career of Karl Meyer and his outstanding contributions to the field of Glycobiology. This international award is given to well-established scientists with currently active research programs who have made widely recognized major contributions to the field of Glycobiology.

Dr. Jamey Marth (Carbon Professor of Biochemistry & Molecular Biology, Mellichamp Professor of Systems Biology, and Director of the Center for Nanomedicine and the SBP Medical Discovery Institute, University of California Santa Barbara) was a student in the mid-sixties in St. Petersburg, Florida, where each year he attended one the nation’s first science immersion summer camps, which still exist today. During the Vietnam war era, as a young American serviceman stationed at Clark Airbase in the Philippines, Jamey reflected on the need to be better educated after returning to the USA and civilian life. He chose to focus on the then new science of molecular biology at the University of Oregon. After earning his Bachelor’s degree, Jamey earned his PhD at the University of Washington under the supervision of then future Nobel laureate Edwin G. Krebs and current Merck VP Roger M. Perlmutter. His thesis project dealt with cloning and characterization of the proto-oncogene lck, which was found to encode a T-cell specific tyrosine kinase. Protein kinases were a hot topic in the eighties and Jamey managed to eclipse other teams who started earlier in making this discovery. At the time, p56lck was only the second src-like tyrosine kinase to be identified from normal mammals, thus allowing the first comparisons of what became the src family of tyrosine kinases. Jamey later showed p56lck is regulated by translational mechanisms that are usurped by viral mutagenesis, which earned the then young graduate student multiple high impact publications and the recognition of the kinase and signal transduction research communities.

After completing his PhD, Jamey continued working on hemopoietic tyrosine kinases with Roger Perlmutter in Seattle and acquired expertise in mouse transgenesis at the Cold Spring Harbor Laboratory. After a brief stint in the biopharmaceutical industry at Oncogen Corp., in 1989 Jamey was recruited to a position at the Biomedical Research Centre and became and as an Assistant Professor at the University of British Columbia. He continued to study the mechanisms of T-lymphocyte maturation and activation, and produced the first transgenic and gene-targeted mouse models in British Columbia. Jamey’s laboratory laid the groundwork for conditional gene targeting by applying the Cre-loxP recombination system to mouse transgenesis for the first time. This technique was further validated as a way to control gene mutagenesis among specific tissues and cells of intact animals and continues to be an essential experimental approach enabling groundbreaking discoveries by many laboratories in disparate fields.

In Canada, John Schrader introduced Jamey to Harry Schachter, who sparked Jamey’s interest in glycobiology. This led to a close collaboration on the study of complex N-glycans, which was tackled by investigating multiple mouse models harboring dysfunctional Mgat1, Mgat2, Mgat3, Mgat4a, and Man2a1 genes. This demonstrated the essential contributions of complex N-glycans not just in embryogenesis, but also in unexpected physiological processes including disease mechanisms. For example, a consensus had prevailed in diabetic physiology that glucose uptake and retention in pancreatic beta cells is controlled by glucokinase, not glucose transport. However, characterization of Mgat4a-null mice and their overlap with the mechanism of obesity-induced diabetes in multiple publications elegantly demonstrated the single complex N-glycan decorating the glucose transporter GLUT2 regulates its stability at the cell surface, thereby regulating glucose uptake. Thus, it was found glucose uptake determines the appropriate rate and timing of glucose-6-phosphate formation in regulating insulin secretion. This seminal contribution from Jamey and his team established the importance of N-glycosylation and its regulation in a disease for which gene variation is not the primary cause. In other studies, Jamey’s laboratory discovered a novel mechanism of autoimmune disease that is induced by immune recognition of aberrant protein glycosylation, thereby identifying the unexpected origin of another common disease.

In 1995, Jamey returned to the United States with the support of Nobel laureate Dr. George Palade, as well as Marilyn Farquhar, Ajit Varki, and other colleagues, and was appointed as a Howard Hughes Investigator and Professor of Cellular and Molecular Medicine at UCSD. By then, his research group was entirely dedicated to the biology of protein glycosylation. During the next decade, his investigations of additional glycosylation defects in mouse models, such as the disruptions of various sialyltransferase genes, further demonstrated the significance of glycosylation in hemostasis and sepsis. Those studies enabled his laboratory’s subsequent remarkable finding that the Ashwell-Morell receptor operates in a recognition mechanism involving endogenous protein aging and turnover by de-sialylation, as was first suggested by Gilbert Ashwell and Anatol Morell almost five decades earlier. The large collection of mouse strains generated by Jamey’s laboratory, which he has deposited with JAX, is now a valuable resource for the scientific community, and should lead to other important discoveries of the biological roles of specific glycans and their receptors.

Since 2009, Jamey has been at the University of California Santa Barbara, where he took leadership of the newly founded Center for Nanomedicine. In addition to his ongoing research, he developed and implemented a new curriculum in Cell Biology and Bioengineering at UCSB that introduced the fascinating world of glycobiology to undergraduate students and future life scientists of high school age, as Jamey himself experienced during his early immersion into science. The 2017 Karl Meyer Lectureship Award recognizes Jamey’s enduring dedication to glycobiology and seminal contributions, which have highlighted the functional roles of glycans across the broad biomedical community.

¹ To whom correspondence should be addressed: email, [email protected]
² Drs. Christopher West (University of Georgia) and Thierry Hennet (University of Zurich) are gratefully acknowledged for contributing the bulk of the writing in these essays.