Dr. Lawrence Tabak's laboratory studies the functions and biosynthesis of O-glycans. Mucin-glycoproteins are heavily decorated with carbohydrate side-chains, termed O-glycans, which are often clustered within repeating amino acids sequences of the protein (tandem repeats). Functionally, membrane-bound mucins are involved in signal transduction events, whereas secreted mucins contribute to the formation of extracellular matrix or to the gel-like mucus coat which envelopes mucosal surfaces of the body thereby forming the most exterior face of the innate immune system. Although it is known that O-glycans are ubiquitous among proteins, the precise nature of the “O-glycome” remains to be defined. We have approached this by both top-down and bottom-up proteomic studies as well as investigations of the substrate specificities of the multi-gene family of enzymes that are responsible for the formation of O-glycans, the UDP-GalNAc:polypeptide N-Acetylgalactosaminyltransferases (GalNAcTs).
Lawrence A. Tabak, D.D.S., Ph.D. is the Principal Deputy Director of the National Institutes of Health (NIH). He served as Acting NIH Director from December 20, 2021, to November 8, 2023. Dr. Tabak was appointed as the NIH Principal Deputy Director and the Deputy Ethics Counselor in August 2010 following his tenure as Director of the National Institute of Dental and Craniofacial Research from 2000-10.
Prior to joining NIH, Dr. Tabak served as the senior associate dean for research and professor of dentistry and biochemistry & biophysics in the School of Medicine and Dentistry at the University of Rochester in New York. A former NIH MERIT recipient, Dr. Tabak has received several honors and awards for his work including election to membership in the Institute of Medicine of the National Academies. He has also received teaching awards for his work with both graduate and medical students.
- Ji S, Samara NL, Revoredo L, Zhang L, Tran DT, Muirhead K, et al. A molecular switch orchestrates enzyme specificity and secretory granule morphology. Nat Commun. 2018 Aug 29;9(1):3508. doi: 10.1038/s41467-018-05978-9.
- May C, Ji S, Syed ZA, Revoredo L, Daniel EJP, Gerken TA, et al. Differential splicing of the lectin domain of an O-glycosyltransferase modulates both peptide and glycopeptide preferences. J Biol Chem. 2020 Aug 28;295(35):12525-125320. doi: 10.1074/jbc.RA120.014700. Epub 2020 Jul 15.
- Zhang L, Mann M, Syed Z, Reynolds HM, Tian E, Samara NL, et al. Furin cleavage of the SARS-CoV-2 spike is modulated by O-glycosylation. Proc Natl Acad Sci U S A. 2021 Nov 23;118(47):e2109905118. doi: 10.1073/pnas.2109905118.
- Yang S, Wang Y, Mann M, Wang Q, Tian E, Zhang L, et al. Improved online LC-MS/MS identification of O-glycosites by EThcD fragmentation, chemoenzymatic reaction, and SPE enrichment. Glycoconj J. 2021 Apr;38(2):145-156. doi: 10.1007/s10719-020-09952-w. Epub 2020 Oct 17.
- Verzijl C, Oldoni F, Loaiza N, Wolters JC, Rimbert A, Tian E, et al. A novel role for GalNAc-T2 dependent glycosylation in energy homeostasis. Mol Metab. 2022 Jun;60:101472. doi: 10.1016/j.molmet.2022.101472. Epub 2022 Mar 15.
- Yang W, Tian E, Chernish A, McCluggage P, Dalal K, Lara A, et al. Quantitative Mapping of the in vivo O-GalNAc Glycoproteome in Mouse Tissues Identifies GalNAc-T2 O-glycosites in Metabolic Disorder. Proc Natl Acad Sci U S A. 2023 Oct 24;120(43):e2303703120. doi: 10.1073/pnas.2303703120. Epub 2023 Oct 20.