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Biochemistry Department - Primary Faculty

Thomas Gerken, Ph.D.

Professor

Education

  • Ph.D: Case Western Reserve University, 1977
  • Postdoc: Case Western Reserve University

Research Interests

Our lab studies mucus glycoproteins (mucins) and mucin-type O-glycosylation with a focus on understanding the biosynthesis of mucin type O-glycans.  Mucin-type O-glycosyaltion is an ubiquitous and essential post-translational modification of proteins traversing the secretory pathway in higher organisms which serves many biological functions from protecting cell surfaces to regulating protease cleavage sites of peptide hormones.  O-glycosylation is extremely important in development and altered O-glycosylation is a hallmark of many cancers. Work in our lab has focused on three major areas:

1) Developing analytical approaches for identifying and quantifying sites of O-glycosylation for tissue based glyco-proteomics studies.

2) Characterizing the peptide and glycopeptide substrate specificity of the glycosyltransferases that initiate O-glycosylation.  Using a series of random peptide and glycopeptide substrates we have obtained peptide sequence motifs for most of the GalNAc-T isoforms showing unique and overlapping specificity.  Our studies have revealed that the activity of many of these transferases are significantly enhanced by prior substrate GalNAc glycosylation. This suggests that O-glycosylation may be regulated by prior remote and neighboring glycosylation in very specific manners.  In collaboration with X-ray crystallographers (L. Tabak at the NIH and R. Hurtado-Guerrero, Zaragoza Spain) we are now beginning to understand the molecular orgins of these activities.

3) Developing a novel approach to predict sites of O-glycosylation.  In collaboration with M-L. Leung, (Univ. Texas El Paso) we are using our random peptide and glycopeptide motifs to predict and identify isoform specific sites of glycosylation.  Our initial GalNAc-T isoform specific predictive approach, ISOGlyP, can be found at http://isoglyp.utep.edu/

Selected References

  • Sletmoen M., Gerken T. A., Stokke B. T., Burchell J., and Brewer C. F.
    “Tn and STn are members of a family of carbohydrate tumor antigens that possess carbohydrate-carbohydrate interactions”
    Glycobiology 28 (7): 437-42 (2018). Read article in PubMedCentral
  • Evans D. R., Venkitachalam S., Revoredo L., Dohey A. T., Clarke E., Pennell J. J., Powell A. E., Quinn E., Ravi L., Gerken T. A., Green J. S., Woods M. O., and Guda K.
    “Evidence for GALNT12 as a moderate penetrance gene for colorectal cancer”
    Hum Mutat 39 (8): 1092-101 (2018). Read article in PubMedCentral
  • de Las Rivas M., Lira-Navarrete E., Daniel E. J. P., Companon I., Coelho H., Diniz A., Jimenez-Barbero J., Peregrina J. M., Clausen H., Corzana F., Marcelo F., Jimenez-Oses G., Gerken T. A., and Hurtado-Guerrero R.
    “The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences”
    Nat Commun 8 (1): 1959 (2017). Read article in PubMedCentral
  • Revoredo L., Wang S., Bennett E. P., Clausen H., Moremen K. W., Jarvis D. L., Ten Hagen K. G., Tabak L. A., and Gerken T. A.
    “Mucin-type O-glycosylation is controlled by short- and long-range glycopeptide substrate recognition that varies among members of the polypeptide GalNAc transferase family”
    Glycobiology 26 (4): 360-76 (2016). Read article in PubMedCentral
  • Haugstad K. E., Hadjialirezaei S., Stokke B. T., Brewer C. F., Gerken T. A., Burchell J., Picco G., and Sletmoen M.
    “Interactions of mucins with the Tn or Sialyl Tn cancer antigens including MUC1 are due to GalNAc-GalNAc interactions”
    Glycobiology 26 (12): 1338-50 (2016). Read article in PubMedCentral
  • Gerken T. A., Revoredo L., Thome J. J., Tabak L. A., Vester-Christensen M. B., Clausen H., Gahlay G. K., Jarvis D. L., Johnson R. W., Moniz H. A., and Moremen K.
    “The lectin domain of the polypeptide GalNAc transferase family of glycosyltransferases (ppGalNAc Ts) acts as a switch directing glycopeptide substrate glycosylation in an N- or C-terminal direction, further controlling mucin type O-glycosylation”
    J Biol Chem 288 (27): 19900-14 (2013). Read article in PubMedCentral
  • Gerken T. A., Jamison O., Perrine C. L., Collette J. C., Moinova H., Ravi L., Markowitz S. D., Shen W., Patel H., and Tabak L. A.
    “Emerging paradigms for the initiation of mucin-type protein O-glycosylation by the polypeptide GalNAc transferase family of glycosyltransferases”
    J Biol Chem 286 (16): 14493-507 (2011). Read article in PubMedCentral
Thomas Gerken Faculty's publications at pubmed