Kelly G. Ten Hagen, Ph.D.
Developmental Glycobiology Section
Building 30, Room 407
30 Convent Drive
Bethesda, MD 20892
Cells of the body are decorated with a variety of carbohydrates (sugars) that serve many diverse functions. These sugars not only act as a protective barrier on the outside of cells, but are also involved in communication and signaling events in many organisms. Our group studies one type of sugar addition to proteins, known as mucin-type O-linked glycosylation, which is initiated by the polypeptide GalNAc transferase (PGANT) enzyme family. Alterations in this type of glycosylation are associated with a number of human diseases. However, the mechanistic roles of this protein modification are not fully understood. Hence, the overarching goal of the Developmental Glycobiology Section is to determine the mechanisms by which O-glycosylation influences basic biological processes to better understand the role of this modification in development and disease. As O-glycosyltransferases are components of the secretory apparatus and are responsible for the modification of secreted and membrane bound proteins, we hypothesize that they play crucial roles in conserved biological functions related to secretion, localization, stability, and function of proteins. Using Drosophila melanogaster, we have determined that at least 5 members of this multigene family are essential for viability. We have also elucidated a specific role for one O-glycosyltransferase in modulating matrix composition and cell adhesion during Drosophila development. We have further demonstrated that O-glycosyltransferases can influence matrix composition during mammalian development, indicating a conserved role for O-glycosylation in the establishment of cellular microenvironments across species. Mechanistically, we have discovered that O-glycosylation modulates secretion and secretory vesicle formation by protecting a conserved cargo receptor from proteolysis. Taken together, our discoveries highlight novel roles for O-glycosylation in conserved cell biological processes that potentially impact all aspects of development. We will continue to elucidate the mechanisms by which O-glycosylation is acting to gain a fundamental understanding of how alterations in glycosylation can contribute to disease onset and progression.
Dr. Ten Hagen received her B.S. (magna cum laude) from Cornell University and earned her Ph.D. in genetics from Stanford University. She served as a Research Assistant Professor at the University of Rochester from 1992-2001, and then as a Senior Research Fellow in the NIDDK, NIH from 2001-2004. She was appointed Chief of the Developmental Glycobiology Unit in the NIDCR, NIH in 2004 and was promoted to Senior Investigator and Chief in 2012. Her laboratory studies the mechanistic roles of protein glycosylation during eukaryotic development. She has served as an Editorial Board Member for The Journal of Biological Chemistry, as the Society for Glycobiology Representative to the International Glycoconjugate Organization and on the Board of Directors as a federal liaison for the Society for Glycobiology. She currently serves on the Promotion and Tenure Committee for NIDCR, the Woman Scientist Advisors Committee and Executive Committee for the NIH, the steering committees for the NIH Glycobiology and Developmental Biology Scientific Interest Groups and as an Editorial Board Member for the journal Glycobiology.
Ji S, Samara NL, Revoredo L, Zhang L, Tran DT, Muirhead K, Tabak LA, Ten Hagen KG. A molecular switch orchestrates enzyme specificity and secretory granule morphology. Nat Commun. 2018;9(1):3508.
Zhang L, Turner B, Ribbeck K, Ten Hagen KG. Loss of the mucosal barrier alters the progenitor cell niche via Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling. J Biol Chem. 2017;292(52):21231-21242.
Tran DT, Masedunskas A, Weigert R, Ten Hagen KG. Arp2/3-mediated F-actin formation controls regulated exocytosis in vivo. Nat Commun. 2015;6:10098.
Zhang L, Syed ZA, van Dijk Härd I, Lim JM, Wells L, Ten Hagen KG. O-glycosylation regulates polarized secretion by modulating Tango1 stability. Proc Natl Acad Sci U S A. 2014;111(20):7296-301.
Tian E, Hoffman MP, Ten Hagen KG. O-glycosylation modulates integrin and FGF signalling by influencing the secretion of basement membrane components. Nat Commun. 2012;3:869.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
Genetics and Genomics
This page was last updated on February 20th, 2018