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Gerald Warren Hart, Ph.D.
Director, Department of Biological Chemistry
Professor of Biological Chemistry
Research Interests: Dynamic O-GlcNAcylation of nuclear and cytosolic proteins
Dr. Gerald W. Hart is the DeLamar Professor of Biological Chemistry and director of the Department of Biological Chemistry at the Johns Hopkins University School of Medicine.
A renowned cell biologist and biochemist, Dr. Hart has been investigating glycoconjugates—specifically, the functions of glycans in the development of cancer, diabetes and neurodegeneration—for more than 40 years.
His work has led to several seminal findings—including the discovery of nuclear and cytoplasmic protein glycosylation by O-linked N-acetylglucosamine—and he has published more than 270 papers in the field of glycosciences.
Dr. Hart joined the Johns Hopkins faculty in 1979.
In 2011 Dr. Hart’s research team was one of two at Johns Hopkins awarded a total of $23 million by the NIH National Heart, Lung and Blood Institute to establish two Programs of Excellence in Glycosciences. The goal is to better understand roles sugars play in the molecular mechanisms of disease.
Among his many professional honors and activities, Dr. Hart has delivered scores of prestigious lectures at universities and professional conferences around the world. He also founded Glycobiology, the field’s leading journal, and served as editor-in-chief for 12 years.
He serves as an associate editor for both Molecular and Cellular Proteomics and The Journal of Biological Chemistry and also sits on the editorial board of ASBMB Today, the journal of The American Society for Biochemistry and Molecular Biology.
Dr. Hart earned his Ph.D. in developmental biology from Kansas State University and completed his post-doctoral training in glycoprotein biochemistry at the Johns Hopkins School of Medicine. He also holds a bachelor’s degree in biology and chemistry from Washburn University.
- Director, Department of Biological Chemistry
- DeLamar Professor of Biological Chemistry
- Professor of Biological Chemistry
Departments / Divisions
- B.S., Washburn University (Kansas) (1971)
- Ph.D., Kansas State University (Kansas) (1977)
Research & Publications
Dr. Hart has been investigating glycoconjugates— particularly the functions of glycans in the development of cancer, diabetes and neurodegeneration—since 1971.
His laboratory conducted some of the earliest studies of cell-surface heparan sulfate proteoglycans; characterized the roles of sulfated glycosaminoglycans and hyaluronic acids in the development of corneal transparency; and performed early studies on the importance of proteoglycan sulfotransferases.
Dr. Hart’s team showed that keratan sulfate I proteoglycan is synthesized by the N-linked biosynthetic pathway and established that the sequon Asn-X-Ser(Thr) is the minimal structural requirement for recognition by N-glycan oligosaccharyltransferase.
His group also performed some of the earliest studies to map N-glycan attachment sites and was among the first to show that N-linked protein glycosylation heterogeneity is site-specific and highly regulated by cellular physiology.
His group further showed that site-specific N-linked glycosylation also is tightly controlled by protein structure at all levels, including the quaternary-structure level.
Dr. Hart’s laboratory purified several of the most important glycosyltransferases and developed methods to use them to probe glycan structures on living cells. He and Johns Hopkins colleague Paul T. Englund, Ph.D., collaborated to elucidate the biosynthetic pathway for GPI anchors.
In the early 1980s, while probing cells with glycosyltransferases, Dr. Hart’s laboratory discovered cytoplasmic and nuclear protein glycosylation by O-linked N-acetylglucosamine (O-GlcNAc).
Since then, the Hart laboratory has published nearly 200 papers on O-GlcNAc. Researchers have identified and cloned the enzymes controlling cycling, characterized O-GlcNAc and its interplay with phosphorylation on hundreds of proteins, and developed many of the tools and methods used to study this modification.
Dr. Hart’s lab studies the crosstalk between dynamic GlcNAcylation and phosphorylation of nucleocytoplasmic proteins in signaling, transcription and cellular metabolism, and the roles of abnormal GlcNAcylation in diabetes, neurodegenerative disease and cancer (oncogene and tumor suppressor proteins, in particular).
They also are focused on developing improved methods (e.g., mass spectrometry and site-specific antibodies) for the study of the O-GlcNAc modification, some of which may have diagnostic value.
Lab Website: Gerald Hart Laboratory
Ma J, Hart GW. "O-GlcNAc profiling: from proteins to proteomes." Clin Proteomics. 2014 Mar 5;11(1):8. doi: 10.1186/1559-0275-11-8.
Bullen JW, Balsbaugh JL, Chanda D, Shabanowitz J, Hunt DF, Neumann D, Hart GW. "Crosstalk between two essential nutrient-sensitive enzymes: O-GlcNAc transferase (OGT) and AMP-activated protein kinase (AMPK)." J Biol Chem. 2014 Feb 21. [Epub ahead of print]
Hascall VC, Wang A, Tammi M, Oikari S, Tammi R, Passi A, Vigetti D, Hanson RW, Hart GW. "The dynamic metabolism of hyaluronan regulates the cytosolic concentration of UDP-GlcNAc." Matrix Biol. 2014 Jan 30. pii: S0945-053X(14)00035-3. doi: 10.1016/j.matbio.2014.01.014. [Epub ahead of print]
Semba RD, Huang H, Lutty GA, Van Eyk JE, Hart GW. "The role of O-GlcNAc signaling in the pathogenesis of diabetic retinopathy." Proteomics Clin Appl. 2014 Jan 21. doi: 10.1002/prca.201300076. [Epub ahead of print]
Hart GW, Ball LE. "Post-translational modifications: a major focus for the future of proteomics." Mol Cell Proteomics. 2013 Dec;12(12):3443. doi: 10.1074/mcp.E113.036491. Epub 2013 Nov 25. No abstract available.
Academic Affiliations & Courses
Graduate Program Affiliation
Graduate Program in Biological Chemistry
Activities & Honors
- Merit Award, National Institute of Child Health and Human Development, 1998
- Honorary Professorship, Shanghai Medical College, 2010
- Karl Meyer Award, Society for Glycobiology, 2006
- Edwin G. Krebs Lectureship Award, University of California, 2007
- International Glycoconjuate Organization Award (Inaugural), 1997
- American Association for the Advancement of Science
- American Chemical Society
- American Diabetes Association
- American Society for Cell Biology
- American Society of Biological Chemistry and Molecular Biology
- Biomedical Carbohydrate Research Center, University of Georgia
- CARBBANK Complex Carbohydrate Structure Database
Board of Overseers
- Howard Hughes Medical Institute Scientific Review Panel
- National Academy of Sciences Glycosciences Task Force
- National Institutes of Health (NIH)
National Institute of General Medical Sciences Glue Grant Assessment Panel
- NIH Cell Biology IRG Reorganization Committee
- Scientific Advisory Board of Stolle Milk Biologics
- Sigma Xi ResearchSociety
- Society for Developmental Biology
- Society for Glycobiology
- Society for Glycobiology
- U.S. Advisory Committee for International Carbohydrate Symposia of American Chemical Society
- Chair, Alliance of Glycobiologists For Detection of Cancer and Cancer Risk
National Cancer Institute Study Section
- Chair, National Institutes of Health (NIH), 1999 - 2000
Pathobiochemistry Study Section
- Founder and Editor in Chief, Glycobiology, 1989 - 2001
- James C. and Elizabeth T. Lee Chair of Biochemistry, University of Alabama at Birmingham, 1993
- President, International Glycoconjuate Organization, 2009 - 2011
Videos & Media
Gerald Hart - Why Too Much Sugar is Toxic
Lectures and Presentations
- NIH Director’s Wednesday Afternoon Lecturer , Washington, DC (12/01/2011)
- Opening Lecturer , Society for Glycobiology Meeting (01/01/2011)
Plenary Lecturer , International Union of Biochemistry and Molecular Biology (IUBMB) (01/01/2011)
Irwin J. Goldstein Lectureship in Glycobiology (01/01/2011)
University of Michigan
- Opening Lecturer , International Symposium on Glycoconjugates XVIII (01/01/2005)
- Opening Lecturer , International Carbohydrate Symposium XXIII (01/01/2006)
Inaugural B. Conner Johnson-John R. Sokatch Lecturer, (01/01/2005)
University of Oklahoma College of Medicine
Keynote Speaker (01/01/2005)
American Heart Association Keystone Meeting
- 20th IUBMB International Congress and 11th Federation of Asian and Oceanian Biochemists and Molecular Biologists (FAOBMB) Congress (01/01/2006)
Adam Nevelle Lecturer (01/01/2003)
University of Dundee
- Keynote Lecturer , Society for Glycobiology Meeting (01/01/2001)