Professor and GRA Eminent Scholar Member of the Complex Carbohydrate Research Center Dr. Hart joined the faculty at UGA on October 1, 2018. Prior to that he was the Director of Biological Chemistry at Johns Hopkins Medical School for 21 years, and on the faculty at JHUSOM for over 40 years. He began his research on glycoconjugates in 1971 as a graduate student, and he has been active in the field ever since. He did some of the very earliest studies on cell surface heparan sulfate proteoglycans (eg. Developmental Biol. (1975) 44, 253). He characterized the roles of sulfated glycosaminoglycans and hyaluronic acids in the development of corneal transparency, and he performed early studies on the importance of proteoglycan sulfotransferases (eg. J. Biol. Chem. (1976) 251, 6513; J. Biol. Chem. (1978) 253, 347). He showed that keratan sulfate I proteoglycan is synthesized by the N-linked biosynthetic pathway, and he established that the sequon, Asn-X-Ser(Thr) is the minimal structural requirement for recognition by the N-glycan oligosaccharyltransferase. Hart’s laboratory performed some of the earliest studies mapping N-glycan attachment sites and they were among the first to show that N-linked protein glycosylation heterogeneity is site specific and highly regulated by cellular physiology (eg. J. Biol. Chem. (1985) 260, 4046). His group further showed that site-specific N-linked glycosylation is tightly controlled also by protein structure at all levels, even up to the level quaternary structure (eg. J. Biol. Chem. (1986) 261:13186-13196). Hart’s laboratory purified several of the most important glycosyltransferases and developed methods to use them to probe glycan structures on living cells (eg. Meth. Enzymol. (1989) 179, 82). In collaboration with Paul Englund’s group, at Johns Hopkins, they elucidated the biosynthetic pathway for GPI-Anchors (eg. Cell (1989) 56, 793). In the early 1980’s, while probing cells with glycosyltransferases, Hart’s laboratory discovered cytoplasmic and nuclear protein glycosylation by O-linked N-acetylglucosamine (O-GlcNAc) (eg. J. Biol. Chem. 259:3308; J. Biol. Chem. 261:8049). Since that time, the Hart laboratory has published over 200 papers on O-GlcNAcylation, identifying and cloning the enzymes controlling cycling, characterizing O-GlcNAcylation and its interplay with phosphorylation on hundreds of proteins, and they have developed many of the tools and methods in use today to study this modification. Recent work is elucidating how nutrients regulate basal transcription by modification of TATA-binding protein. In 1989, Hart founded the leading journal in the field, Glycobiology, serving as Editor-In-Chief until 2001. He is currently an Associate Editor for J. Biological Chemistry, an Associate Editor for Molecular and Cellular Proteomics and was on the board of ASBMB Today. Hart received the first International Glycoconjuate Organization (IGO) Award in 1997, the Karl Meyer Award from the Society for Glycobiology in 2006, the Presidents Innovator Award from Society for Glycobiology in 2019, and served as president of the IGO from 2009-2011. He received the Herbert Tabor Award and the Yamakawa award in 2018, and was elected President of the American Society of Biochemistry and Molecular Biology (ASBMB) in 2018. To date, Hart has published about ~306 papers all in the area of glycosciences. Current Google Scholar H-factor = 120; i10-index=315 Education Education: Post-doctoral — Johns Hopkins University School of Medicine, June 1977 to July 1, 1979 — Glycoprotein Biochemistry Ph.D. — Kansas State University, Spring 1977 — Developmental Biology Bachelor of Sciences — Washburn University, Spring 1971 — Biology and Chemistry Research Research Areas: Cellular & Molecular Neuroscience Epigenetics & Chromatin Cell Biology Glycobiology Cancer Biology Drug Discovery & Development Research Interests: We are studying how nutrients regulate signaling and transcription by O-GlcNAcylation (OGN). OGN is the addition and removal of N-acetylglucosamine from Ser(The) residues of nuclear, cytoplasmic and mitochondrial proteins. The cycling sugar is analogous to phosphorylation and has extensive crosstalk with phosphorylation, both in terms of site occupancy and in the regulation of kinases. Current Projects: 1. Roles of OGN in regulation of transcription, particularly on basal machinery and on RNA polymerase II 2. Develop Optogenetic methods to target the O-GlcNAc transferase to specific substrates. 3. Roles of OGN in diabetes and glucose toxicity. 4. Roles of OGN in regulation of protein translation and in mRNA selection. 5. Interplay between Src kinase and OGN in cancer. 6. Roles of OGN in Alzheimer's Disease. Labs: Hart Selected Publications Selected Publications: Hart, G.W. (2019) Nutrient Regulation of Signaling and Transcription. (Tabor Award Article) J. Biol. Chem. (2019) 294(7) 2211–2231. Stéphan Hardivillé, Partha S. Banerjee, Ebru S. Alpergin, Guanghui Han, Junfeng Ma, Conover C. Talbot Jr., Ping Hu, Michael Wolfgang and Gerald W. Hart (2019) TATA-Box Binding Protein O-GlcNAcylation at T114 regulates formation of the B-TFIID complex and is critical for metabolic gene regulation. Molecular Cell (In Press). https://doi.org/10.1016/j.molcel.2019.11.022 Lagerlöf O, Blackshaw S, Hart GW and Huganir RL (2017) O-GlcNAc transferase regulates excitatory synapse maturity. Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):1684-1689 Junfeng Ma, Ting Liu, An-Chi Wei, Partha Banerjee, Brian O’Rourke, Gerald W. Hart. (2015) Protein O-GlcNAcylation regulates cardiac mitochondrial function. J. Biol. Chem. 290, 29141-29153. (Paper of the Week & Top Glycobiology Paper of the Year). Partha S. Banerjee, Junfeng Ma and Gerald W. Hart (2015) Diabetes Associated Dysregulation of O-GlcNAcylation in Rat Cardiac Mitochondria. PNAS 112, 6050-6055 Lagerlöf O, Blackshaw S, Hart GW and Huganir RL (2016) The nutrient sensor OGT regulates feeding in αCaMKII-positive neurons of the PVN. Science 351, 1293-1296 Jeffrey R. Erickson, Laetitia Pereira, Lianguo Wang, Guanghui Han, Amanda Ferguson, Khanha Dao, Ronald J. Copeland, Florin Despa, Gerald W. Hart, Crystal M. Ripplinger, and Donald M. Bers (2013) Diabetic Hyperglycemia activates CaMKII and Arrhythmias by O linked Glycosylation. Nature 502(7471):372-6.doi: 10.1038/nature12537. John W. Bullen, Jeremy Balsbaugh, Dietbert Neumann, Jeffrey Shabanowitz, Donald F. Hunt and Gerald W. Hart (2014) Dynamic Crosstalk between two essential nutrient-sensitive enzymes: O-GlcNAc Transferase (OGT) and AMP-activated protein kinase (AMPK)” J. Biol. Chem. 289:10592-10606.. Stephen A. Whelan, Wagner Dias, T. Lakshmanan, M. Daniel Lane, Gerald W. Hart (2009) Regulation of Insulin Receptor 1 (IRS-1)/AKT Kinase Mediated Insulin Signaling by O-linked β-N-acetylglucosamine (O-GlcNAc) in 3T3-L1 Adipocytes .J. Biol. Chem. 285, 5204-5211. Zihao Wang; Namrata Udeshi; Chad Slawson; Philip Compton; Jeffrey Shabanowitz; Donald F. Hunt; and Gerald W. Hart (2010)Extensive Crosstalk Between GlcNAcylation and Phosphorylation Regulates Cytokinesis Science Signaling 3, (104) ra2 (PMCID: PMC2866299) Zihao Wang; Namrata Udeshi; Meaghan O’Malley; Jeffrey Shabanowitz; Donald F. Hunt; and Gerald W. Hart (2010) Highly Specific Enrichment and Site-Mapping of O-GlcNAcylation Using Chemoenzymatic Tagging, Solid-Phase Photocleavage, and Electron Transfer Dissociation Mass Spectrometry. Molecular and Cellular Proteomics 9: 153-160. (PMCID: PMC2808261) Stella Ranuncolo1, George Wright2, Wenming Xiao3, Jason Piotrowski1, Alfonso Fernandez1, Kaoru Sakabe4, John Hanover5, Gerald W. Hart4, and Brian A. Lewis (2012) Evidence of the Involvement of O-GlcNAc-modified Human RNA Polymerase II CTD in Transcription in Vitro and in Vivo J. Biol. Chem. 287, 23549-61. PMCID: PMC3390630 Kaoru Sakabe and Gerald W. Hart (2011) O-GlcNAc is Part of the Histone Code Proc. Natl. Acad. Sci. (USA) 107, 19915-19920 (PMCID 2993388) Quira Zeidan, Zihao Wang, Antonio De Maio and Gerald W. Hart (2010) O-GlcNAc Cycling Enzymes Associate with the Translational Machinery and Modify Many Core Ribosomal Proteins. Molecular Biology of the Cell 21, 1922-1936 (PMCID: PMC2883937) Wagner B. Dias, Win D. Cheung, Zihao Wang, and Gerald W. Hart (2009) Regulation of Calcium/Calmodulin-dependent Kinase IV by O-GlcNAc Modification. J. Biol. Chem. 284, 21327–21337. (PMCID: PMC2755857) Zihao Wang, Kyoungsook Park, Frank Comer1, Linda C. Hsieh-Wilson, Christopher D. Saudek, and Gerald W. Hart (2008) Site-Specific GlcNAcylation of Human Erythrocyte Proteins: Potential Biomarker(s) for Diabetes Mellitus. Diabetes 58, 309-317 (PMCID: PMC2628603) Win D. Cheung, Kaoru Sakabe, Michael P. Housley, Wagner B. Dias, and Gerald W. Hart (2008) O-GlcNAc transferase substrate specificity is regulated by MYPT1 and other interacting proteins. J. Biological Chemistry 283, 33935–33941 (PMCID: PMC2590692) Of Note Of note: 2019 President’s Innovator Award, Society for Glycobiology. 2018 Yamakawa Award from the Japanese Glycobiology Society (JCCG) 2018 Herbert Tabor Award from the American Society for Biochemistry and Molecular Biology President American Society for Biochemistry and Molecular Biology (ASBMB) -2018-2020 Named First Paul & Christine Englund Endowed Professor NIH Director’s Wednesday Afternoon Lecturer (WALS), Dec. 2011, Washington, DC Opening Lecture, 2011 Society for Glycobiology Meeting, Seattle, WA. Plenary Lecture 2011 IUBMB Cell Signaling Networks, Merida Mexico 2011 Irwin J. Goldstein Lectureship in Glycobiology, Univ. of Michigan. 2010 named, Honorary Professor of Shanghai Medical College, Fudan Univ., Shanghai, China 2009-2011 President, International Glycoconjugate Organization (IGO) 2009 - Hall of Fame, Topeka High School 2008 Alumni Fellow, School of Arts & Sciences Kansas State University 2007 Edwin G. Krebs Lectureship Award, UC Davis, CA. 11th Annual Lecture of Institutes Cell & Dev. Biol., Stonybrook, NY. 2006 Karl Meyer Award from Society for Glycobiology, Los Angeles, CA. Opening Lecturer, Glyco XVIII (2005), Florence, Italy; 2007 Adrouny Lecturer, Tulane Plenary Lecturer XXIII Intl. Carbohydrate Symp 2006, Whistler, Canada Inaugural B.Conner Johnson-John R. Sokatch Lecturer, Univ. Oklahoma Med. Sch.; Keynote Speaker American Heart Association Keystone Meeting, 2005. IUBMB Lecturer, 20th IUBMB Intl. Congress of Biochem. & Molec. Biol. and 11th FAOBMB Congress, June 2006, Kyoto, Japan 2003 Adam Nevelle Lecturer, Dundee Scotland Keynote Lecturer, Nov. 2001 Society for Glycobiology Meeting, Boston, MA. December 2000 – Sept. 30, 2014 – Visiting Professor, Division of Molecular Sciences, Imperial College of Science and Technology, London, U.K. 1998 –present, Elected USA Representative to Intl. Glycoconjugate Organization (IGO) 1999 – 2000 Chair, Pathobiochemistry Study Section, NIH 1998 – NIH Merit Award From Natl Inst. Child Health & Human Development. 1997 - First International Glycoconjuate Organization (IGO) Award Recipient - Zurich,Switzerland (most prestigious award in the field of Glycobiology;every other year at IGO meetings). 1997 - Reilly Lecturer, Univ. of Notre Dame. Elected to the Council of the American Society of Biochemistry and Molecular Biology (ASBMB) - 1995-1998 1995 President, Society for Glycobiology (formerly Society of Complex Carbohydrates) Elected to Co-Chair the 1995 and Chair the 1997 Gordon Conference on Glycobiology Member, Pathobiochemistry Study Section-July 1, 1995-June 30, 1999 June 1, 1993: Named James C. and Elizabeth T. Lee Chair of Biochemistry at UAB December 1993: Appointed Associate Director for Basic Science Research, UAB Comprehensive Cancer Center Dean’s Lecturer: Johns Hopkins University Medical School, 1991 & 1998 1990: Elected to Board of Directors of Society for Complex Carbohydrates 1989: Winzler Memorial Lectureship at University of Florida Banquet Speaker at the 1988 UCLA Keystone Symposium on Glycobiology Established Investigator, American Heart Association, July 1, 1983 to June 30, 1988 Fellow of the Jane Coffin Childs Memorial Fund for Medical Research 1975 Recipient of the H.H. Haymaker Award for Excellence in Graduate Student Research Company Honorman, Hospital Corps School, Balboa Naval Hospital, San Diego, CA
