Assistant Professor
Division of Endocrinology, Diabetes and Metabolism

Education and Training:
M.Sc. (Chemistry) 1975, University of Canterbury, Christchurch, New Zealand
Ph.D. (Biochemistry) 1981, University of Otago, Dunedin, New Zealand
Postdoctoral Fellow 1981-1985, NIH, Bethesda, MD
Research Associate 1985-1989, University of Toronto,Toronto, Canada
Assistant Professor, Dept of Medicine, University of Alabama at Birmingham, (1989-present)

Center Affiliations:
Comprehensive Diabetes Center

GBS Program Affiliations:
Cell, Molecular & Developmental Biology

Research Interest:
The central research interest in our laboratory is the study of O-linked glycosylation. From our early work describing transforming growth factor-alpha (TGF-α) gene expression, we discovered that the TGF-αpromoter contained Sp1 recognition sites and that O-GlcNAc modification of the Sp1 transcription factor could modulate gene transcription. This post-translational modification involves the addition of O-linked N-Acetyl-glucosamine (O-GlcNAc) to serine and threonine amino acids of nucleo-cytoplasmic proteins, many of which are transcriptional or regulatory proteins. We showed that Sp1 could be degraded by the proteasome, a protein complex essential in removing unwanted proteins, and that the activity of the proteasome was partially dependent on O-GlcNAcylation. Thus, in times of low nutrition (low glucose) we expect proteasome function to increase and remove those proteins involved in cell propagation such as Sp1 The 2 enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) add or remove O-GlcNAc respectively from proteins. We cloned a naturally occurring OGA mutant that has the catalytic region spliced out of the gene (OGAGK), and that when this dominant-negative protein was over-expressed, caused a net increase in O-GlcNAc modification of many cellular proteins, such as observed in nutrient-related diseases.Specifically, increased O-GlcNAcylation in beta cells, mammary glands, lens or skeletal muscle, cell development and function is impaired and can be partly attributed to reduced proteasome activity. Our studies have provided a link between the nutrient status of a cell or organism with a mechanism that may explain many of the pathologies associated with increased glucose metabolism. The implications for the treatment of certain diseases such as diabetes and muscular degeneration may rest in our fundamental understanding on how O-Glycosylation regulates cellular function.


1.     Co-P.I. NIH/NIDDK, R01 DK55262, October 1998-September 2001. “Role of intracellular O-GlcNAc in glucotoxicity to the cell”; Dr. Jeffrey Kudlow, P.I.
2.     Co-P.I. NIH/NIDDK, R01 DK43652, June 1991-May 2005. “Growth factor involvement in pituitary function”; Dr. Jeffrey Kudlow, P.I.
3.     Co-P.I. NIH, R01 CA09502, August 2003-July 2006. “Proteasome regulation by O-glycosylation”;
P.I. 2007-2008.
4.     P.I. NIH/NIDDK. R01 DK043652, April 2006-March 2012. “O-Glycosylation in breast cancer”.

Selected Publications:

  1. Gan, Y, Paterson, AJ, Zhang, Y, Jiang, J, and Frank, SJ, Functional collaboration of insulin-like growth factor-1 receptor (IGF-1R), but not insulin receptor (IR), with acute GH signaling in mouse calvarial cells. Endocrinology, (2014). 155(3): p. 1000-9. PMC: 3929739
  2. Zou, L, Zhu-Mauldin, X, Marchase, RB, Paterson, AJ, Liu, J, Yang, Q, and Chatham, JC, Glucose deprivation-induced increase in protein O-GlcNAcylation in cardiomyocytes is calcium-dependent. J Biol Chem, (2012). 287(41): p. 34419-31. PMC: 3464547
  3. Huang, P, Ho, SR, Wang, K, Roessler, BC, Zhang, F, Hu, Y, Bowe, DB, Kudlow, JE, and Paterson, AJ, Muscle-specific overexpression of NCOATGK, splice variant of O-GlcNAcase, induces skeletal muscle atrophy. Am J Physiol Cell Physiol, (2011). 300(3): p. C456-65. PMC: 3063975
  4. Ho, SR, Wang, K, Whisenhunt, TR, Huang, P, Zhu, X, Kudlow, JE, and Paterson, AJ, O-GlcNAcylation enhances FOXO4 transcriptional regulation in response to stress. FEBS Lett, (2010). 584(1): p. 49-54. PMC: 2802345
  5. Zhang, F, Hu, Y, Huang, P, Toleman, CA, Paterson, AJ, and Kudlow, JE, Proteasome function is regulated by cyclic AMP-dependent protein kinase through phosphorylation of Rpt6. J Biol Chem, (2007). 282(31): p. 22460-71. PMC:
  6. Toleman, C, Paterson, AJ, and Kudlow, JE, Location and characterization of the O-GlcNAcase active site. Biochim Biophys Acta, (2006). 1760(5): p. 829-39. PMC:
  7. Bowe, DB, Sadlonova, A, Toleman, CA, Novak, Z, Hu, Y, Huang, P, Mukherjee, S, Whitsett, T, Frost, AR, Paterson, AJ, and Kudlow, JE, O-GlcNAc integrates the proteasome and transcriptome to regulate nuclear hormone receptors. Mol Cell Biol, (2006). 26(22): p. 8539-50. PMC: 1636782
  8. Liu, K, Paterson, AJ, Zhang, F, McAndrew, J, Fukuchi, K, Wyss, JM, Peng, L, Hu, Y, and Kudlow, JE, Accumulation of protein O-GlcNAc modification inhibits proteasomes in the brain and coincides with neuronal apoptosis in brain areas with high O-GlcNAc metabolism. J Neurochem, (2004). 89(4): p. 1044-55. PMC:
  9. Zhang, F, Su, K, Yang, X, Bowe, DB, Paterson, AJ, and Kudlow, JE, O-GlcNAc modification is an endogenous inhibitor of the proteasome. Cell, (2003). 115(6): p. 715-25. PMC:
  10. Roh, M, Paterson, AJ, Asa, SL, Chin, E, and Kudlow, JE, Stage-sensitive blockade of pituitary somatomammotrope development by targeted expression of a dominant negative epidermal growth factor receptor in transgenic mice. Mol Endocrinol, (2001). 15(4): p. 600-13. PMC:
  11. Liu, K, Paterson, AJ, Chin, E, and Kudlow, JE, Glucose stimulates protein modification by O-linked GlcNAc in pancreatic beta cells: linkage of O-linked GlcNAc to beta cell death. Proc Natl Acad Sci U S A, (2000). 97(6): p. 2820-5. PMC: 16013
  12. Xie, W, Chow, LT, Paterson, AJ, Chin, E, and Kudlow, JE, Conditional expression of the ErbB2 oncogene elicits reversible hyperplasia in stratified epithelia and up-regulation of TGFalpha expression in transgenic mice. Oncogene, (1999). 18(24): p. 3593-607. PMC:
  13. Su, K, Roos, MD, Yang, X, Han, I, Paterson, AJ, and Kudlow, JE, An N-terminal region of Sp1 targets its proteasome-dependent degradation in vitro. J Biol Chem, (1999). 274(21): p. 15194-202. PMC:
  14. Shin, TH, Paterson, AJ, and Kudlow, JE, p53 stimulates transcription from the human transforming growth factor alpha promoter: a potential growth-stimulatory role for p53. Mol Cell Biol, (1995). 15(9): p. 4694-701. PMC: 230712
  15. Paterson, AJ and Kudlow, JE, Regulation of glutamine:fructose-6-phosphate amidotransferase gene transcription by epidermal growth factor and glucose. Endocrinology, (1995). 136(7): p. 2809-16. PMC