Lawrence A. Tabak, D.D.S., Ph.D. : NIDDK

Lawrence A. Tabak, D.D.S., Ph.D.

NIDDK, National Institutes of Health
Building 31, Room 2C39
31 Center Dr.
Bethesda, MD 20892-2290
Tel: 301-496-3571
Fax: 301-402-2185

Education / Previous Training and Experience:
Dr. Lawrence A. Tabak was appointed as the seventh director of the NIDCR in September 2000. In addition, he was appointed acting deputy director of NIH in November of 2008. Prior to joining NIH, Dr. Tabak was 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 being elected a fellow of the AAAS and a member of the Institute of Medicine of the National Academies. He has also received teaching awards for his work with both graduate and medical students.

Dr. Tabak received a B.S. from City College of the CUNY (1972), a D.D.S. degree from Columbia University (1977) and a Ph.D. from SUNY at Buffalo (1981).

Research Statement:

Mucin-type glycoproteins have been conserved throughout much of evolution. The first committed step in mucin biosynthesis is directed by a family of glycosyltransferases termed the UDP GalNAc:polypeptide N-acetylgalactosaminyltransfersaes (ppGalNAcTs) that transfer GalNAc to the serine and threonine residues of the protein core (Ten Hagen et al., 2003). Available evidence indicates that there are twenty ppGalNAcT's in mammals. Why nature requires so many isoforms of this enzyme to perform this seemingly simple reaction has been the subject of intense investigation in our laboratory.

Substrate definition and enzymatic function – We are employing X ray diffraction to solve the structures of the ppGalNAcT's (Fritz et al., 2004; Fritz et al., 2006) and kinetic approaches (Raman et al., 2008). Insights from these structures are helping to inform our current efforts to define the native substrates of each isoform. To add to the challenge, in vitro evidence suggests that O-glycosylation proceeds in a hierarchical manner, with one subclass of ppGalNAcT's required to glycosylate specific threonines and serines prior to the action of other ppGalNAcT's (Pratt et al., 2004).

O-glycan synthesis and function – Many of the ppGalNAcT's exhibit unique temporal and spatial patterns of expression during development (Kingsley et al., 2001). We are systematically ablating the expression of ppGaNAcT's in mice to better understand the role of O-glycans in vivo (e.g. Tenno et al., 2007).

Selected Publications:

Raman, J, Fritz, TA., Gerken, TA, Jamison, O, Live, D, Liu,M and Tabak, LA

The Catalytic and Lectin Domains of UDP-GalNAc:Polypeptide -N-Acetylgalactosaminyltransferase Function in Concert to Direct Glycosylation Site Selection. J. Biol. Chem., 2008; 283: 22942 – 2295, 2008.

Tenno M, Ohtsubo K, Hagen FK, Ditto D, Zarbock A, Schaerli P, von Andrian UH, Ley K, Le D, Tabak LA, Marth JD Initiation of protein O glycosylation by the polypeptide GalNAcT-1 in vascular biology and humoral immunity. Mol Cell Biol(27): 8783-96, 2007. [Full Text/Abstract]

Fritz TA, Raman J, Tabak LA  Dynamic association between the catalytic and lectin domains of human UDP-GalNAc:polypeptide alpha -N-acetylgalactosaminyltransferase-2.  J Biol Chem , 2006. [Full Text/Abstract]

Pratt MR, Hang HC, Ten Hagen KG, Rarick J, Gerken TA, Tabak LA, Bertozzi CR  Deconvoluting the functions of polypeptide N-alpha-acetylgalactosaminyltransferase family members by glycopeptide substrate profiling.  Chem Biol (11): 1009-16, 2004. [Full Text/Abstract]

Fritz TA, Hurley JH, Trinh LB, Shiloach J, Tabak LA  The beginnings of mucin biosynthesis: the crystal structure of UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferase-T1.  Proc Natl Acad Sci U S A (101): 15307-12, 2004. [Full Text/Abstract]

Ten Hagen KG, Fritz TA, Tabak LA  All in the family: the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases.  Glycobiology (13): 1R-16R, 2003. [Full Text/Abstract]

Kingsley PD Hagen KG Maltby KM Zara J Tabak LA Diverse spatial expression patterns of UDP-GalNAc:polypeptide N-acetylgalactosaminyl-transferase family member mRNAs during mouse development. Glycobiology(10): 1317-23, 2000. [Full Text/Abstract]

Page last updated: January 13, 2009

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