Gerald Hart

Hart, Gerald

Georgia Research Alliance William Henry Terry, Sr. Eminent Scholar in Drug Discovery, and Professor of Biochemistry and Molecular Biology
Georgia Research Alliance William Henry Terry, Sr. Eminent Scholar in Drug Discovery, and Professor of Biochemistry and Molecular Biology We discovered O-GlcNAcylation (OGN) in the early 1980s. OGN is the cycling of N-acetylglucosamine on and off serine or threonine residues on nuclear and cytoplasmic proteins. OGN occurs on over four-thousand proteins where it serves as a nutrient sensor with extensive crosstalk with phosphorylation to regulate many cellular processes, including signaling, transcription, translation and mitochondrial functions. There is a rapidly growing literature suggesting that O-GlcNAcylation contributes to the properties and progression of cancer cells. O-GlcNAc cycling is universally elevated in cancer cells and, indeed, preventing increased O-GlcNAcylation can block cancer progression. Aberrant expression and activities of O-GlcNAc cycling enzymes, especially OGT, have been reported in all human cancers studied to date. Altered cellular metabolism is a major hallmark of cancer. Glucose uptake and glycolysis are accelerated in cancer cells (“Warburg Effect”), which gives cancer cells an advantage for intensive growth and proliferation. O-GlcNAc-dependent regulation of signaling pathways, transcription factors, enzymes, and epigenetic changes are all likely involved in metabolic reprograming of cancer. Several researchers have proposed that inhibition of hyper-O-GlcNAcylation could be a potential novel therapeutic target for cancer treatment. It has also been proposed that aberrant O-GlcNAcylated proteins might be novel biomarkers of cancer. Currently, our laboratory is focused on the roles of OGN on -catenin in the functions of WNT signaling and in the epithelial-mesenchymal transition (EMT). In collaboration with Michael Pierce’s laboratory we are also investigating the roles of OGN in mechanisms of tumor cell suppression of the immune system. Google Scholar