15 mars 2018: Prof. Gerald Hart

Jeudi 15 mars 2018
12h30, CMU - Auditoire A. Franceschetti (C150)

Dr. Gerald Hart is a world renowned protein biochemist who has been investigating glycoconjugates for almost five decades, authoring over 270 peer-reviewed articles on this subject alone. He is best known for discovery of nuclear and cytoplasmic protein glycosylation by O-linked N-acetylglucosamine.

Gerald Hart is a very clear and engaging speaker whose seminar covers a spectrum of subjects of broad interest to the research community in the Faculty. Make sure you don’t miss his talk: this Thursday at 12.30PM in C150!

Watch a teaser here

Oliver Hartley , Département de pathologie et immunologie, Faculté de médecine UNIGE
Frédérique Lisacek, Département d'informatique, Section de biologie, Faculté des sciences UNIGE

Gerald W. HART

Paul and Christine Englund Professor & Director
Department of Biological Chemistry
Johns Hopkins University School of Medicine

Photo Hart.jpg

«How Nutrients Regulate Signaling and Transcription»

O-GlcNAcylation cycles on and off thousands of nucleocytoplasmic proteins and has extensive crosstalk with protein phosphorylation. O-GlcNAc cycles on nearly all proteins involved in transcription, where it regulates gene expression in response to nutrients. O-GlcNAc also regulates the cycling of the TATA-binding (TBP) protein on and off DNA during the transcription cycle and is required for TBP to bend DNA.

Targeted, inducible, deletion of the O-GlcNAc Transferase in aCAMKII positive (excitatory) neurons of adult mice results in a morbidly obese mouse with a satiety defect. Thus, O-GlcNAcylation not only serves as a nutrient sensor in all cells, but also is directly involved in appetite regulation. O-GlcNAcylation also plays an important role in the trafficking of the AMPA receptors in neurons and in the development of functional synaptic spines. Recent studies have shown that more than one-half of all human protein kinases are modified by O-GlcNAc and all kinases that have been tested are indeed regulated in some way by the sugar. Abnormal O-GlcNAcylation of CAMKII contributes directly to diabetic cardiomyopathy and to arrhythmias associated with diabetes. Prolonged elevation of O-GlcNAc, as occurs in diabetes, contributes directly to diabetic complications and is a major mechanism of glucose toxicity. Targeted over-expression of OGT to the heart causes severe heart failure in mice, which is reversed when they are crossed with mice having OGA over-expressed in their hearts. Drugs that elevate O-GlcNAcylation in the brain, which prevents hyperphosphorylation, appear to be of benefit for the treatment of Alzheimer’s disease in animal models. To date, all cancers have elevated O-GlcNAc cycling, which may play a key role in the regulation of metabolism in cancer cells.

Gerald Warren Hart, Ph.D. – Program Director
is the Paul & Christine Englund Professor and Director of Biological Chemistry at Johns Hopkins. He has served as the Director of Biological Chemistry for ~20 years. He is an Associate Editor of J. Biological Chemistry and of Molecular and Cellular Proteomics and an Editor of BBRC. He founded the journal Glycobiology in 1989, now the leading journal in the field and served as its Editor-In-Chief for 12 years. During his graduate career, he performed some of the earliest studies on cell surface heparan sulfates and on the roles of proteoglycans and sulfotransferases in corneal transparency. During his postdoctoral work, he determined the minimal sequence requirement for N-glycosylation (-Asn-X-Ser-) and showed that corneal keratin sulfate is made via the N-glycan biosynthetic pathway. Hart’s laboratory discovered O-GlcNAcylation, he co-led elucidation of GPI anchor biosynthesis with Paul Englund’s group, and his lab documented the importance of protein structure for N-glycosylation. His lab discovered the extensive crosstalk between O-GlcNAc and phosphorylation, which regulates transcription and signaling and underlies the etiology of diabetes, neurodegenerative disease, cardiovascular disease and cancer. ~300 publications; Google H-factor = 109; i10-index=300.

Some Reviews:

Stéphan Hardivillé and Gerald W. Hart (2014)
Nutrient Regulation of Transcription, Signaling, and Cell Physiology by O-GlcNAcylation. Cell Metabolism Volume 20, Issue 2, 5 August 2014, Pages 208–213

Gerald W. Hart, Chad Slawson, Genero Ramirez-Correa, and Olof Lagerlof (2011)
Crosstalk Between O-GlcNAcylation and Phosphorylation:  Roles in Signaling, Transcription and Chronic Disease. Annual Review of Biochemistry 80:825-58. PMCID: PMC3294376

Quira Zeidan and Gerald W. Hart (2010)
Crosstalk between GlcNAcylation and phosphorylation: implications for signal transduction and transcription. J. Cell Sci. 123, 13-22. (PMCID: PMC2794709)

Gerald W. Hart (2016)
Nutrient Regulation of Transcription and Signaling by O-GlcNAcylation Proceedings of the International Beilstein Symposium on Chemistry & Time. Martin G. Hicks and Carsten Kettner, Eds. Perspectives in Science (2015) 6, 49-57

15 mars 2018

Frontiers in biomedicine