Jeffrey Esko

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Jeffrey David Esko, Ph.D.,M.D. (h.c) is currently a Distinguished Professor of Cellular and Molecular Medicine [1] and Co-Director of the Glycobiology Research and Training Center [2] at the University of California, San Diego. His research has focuses on understanding the structure, biosynthesis and biological roles of proteoglycans in mammalian cells and model organisms. Esko popularized [3] [ citation needed ] proteoglycans through his pioneering genetic and functional studies in cells and model organisms. He discovered the dependence of tumor formation on heparan sulfate, the first small molecule inhibitors of heparan sulfate, the action of proteoglycans as receptors for hepatic lipoprotein clearance and for delivery of therapeutic agents. Esko cofounded Zacharon Pharmaceuticals. [4] He was an editor and author of the first textbook in the Glycobiology field, Essentials of Glycobiology. [5]

Contents

Education

Esko received his Ph.D.in Biochemistry at the University of Wisconsin in Madison. After an independent fellowship at the Molecular Biology Institute at the University of California,Los Angeles, he moved to the University of Alabama at Birmingham and then to the Department of Cellular and Molecular Medicine at the University of California, San Diego in 1996 to help build a program in Glycobiology. He has published over 250 scholarly papers, reviews and book chapters and was editor/author of the first textbook in the field, Essentials of Glycobiology (1st and 2nd editions). [5] [6] The 2nd edition of Essentials of Glycobiology is made freely available online and became one of the pioneering textbooks to be distributed electronically. [6] [7]

Early work

Esko’s work has focused on the structure, assembly and function of heparan sulfate proteoglycans for the last 30 years. In the 1980s, Esko was the first to isolate and characterize animal cell mutants altered in the assembly of heparan sulfate. [8] His studies of the mutants revealed regulatory mechanisms that control the composition of glycosaminoglycans in cells. The mutants provided the first genetic evidence showing that heparan sulfate was required for growth factor activation and tumor growth. These cell lines continue to be used by hundreds of laboratories worldwide and they serve as the benchmark for analysis of proteoglycan deficiencies in other systems, including zebrafish, fruit flies, nematodes and mice. [3] Since 1996, Esko has focused on the development of mutant mice bearing conditional mutations in enzymes involved in heparan sulfate assembly. Prof. Esko has developed mass spectrometry methods for identification of proteoglycan core proteins and for characterizing the fine structure of the heparan sulfate chains. [9]

Current Research Interests

Work in his laboratory focuses on the structure, biosynthesis, and function of proteoglycans in development and disease using forward and reverse genetic methods. This includes development of animal models lacking key enzymes involved in proteoglycan assembly; application of genome-wide methods to identify novel genes involved in heparan sulfate assembly; analysis of guanidinylated glycosides that bind to proteoglycans; studies of proteoglycans in lipoprotein metabolism in the liver and macrophages; and studies of proteoglycan-associated receptors with particular emphasis on the vasculature and inflammation. He developed a carrier that exploits proteoglycans for delivery of high molecular weight cargo and used it for enzyme replacement therapy for lysosomal storage disorders. Most recently, he developed a facile method for diagnosis of mucopolysaccharidoses. His work is best described as cross-disciplinary, spanning chemistry, biochemistry, cell biology, genetics, and physiology.

Honors and Boards

His work has been recognized by the Karl Meyer Award (2007), [3] the highest honor from the Society for Glycobiology, the IGO award from the International Glycoconjugate Organization (2011), a MERIT Award from the National Institutes of Health (2000-2010). He won Mizutani research grant in 1995 and 2007 and was recently elected as a Fellow of the American Association for the Advancement of Science. Esko received (January 2010) an honorary doctorate from Uppsala University, Sweden for his outstanding achievement in the field of glycobiology and for being an important collaborator and inspiring partner for Uppsala proteoglycan glycobiologists. [10] He has given several named lectureships, including the Blaffer lecture at MD Anderson and the WALS lecture at the National Institutes of Health. [11] [12] Esko has served on the numerous scientific, advisory, and editorial boards (Journal of Biochemistry, Journal of Biological Chemistry, Journal of Cell Biology, Glycobiology and as an ad hoc reviewer for Proceedings of the National Academy of Sciences, Journal Clinical Investigation, Biochimica Biophysica Acta, Matrix Biology, Nature and Science). Additionally, he served as President of the Society for Glycobiology in 2002-2003 and as Director of the Biomedical Sciences Graduate Program at UCSD.

Related Research Articles

Defined in the narrowest sense, glycobiology is the study of the structure, biosynthesis, and biology of saccharides that are widely distributed in nature. Sugars or saccharides are essential components of all living things and aspects of the various roles they play in biology are researched in various medical, biochemical and biotechnological fields.

Extracellular matrix Network of proteins and molecules outside cells that provides structural support for cells

In biology, the extracellular matrix (ECM) is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and biochemical support to surrounding cells. Because multicellularity evolved independently in different multicellular lineages, the composition of ECM varies between multicellular structures; however, cell adhesion, cell-to-cell communication and differentiation are common functions of the ECM.

In polymer science, the polymer chain or simply backbone of a polymer is the main chain of a polymer. Polymers are often classified according to the elements in the main chains. The character of the backbone, i.e. its flexibility, determines the properties of the polymer. For example, in polysiloxanes (silicone), the backbone chain is very flexible, which results in a very low glass transition temperature of −123 °C. The polymers with rigid backbones are prone to crystallization in thin films and in solution. Crystallization in its turn affects the optical properties of the polymers, its optical band gap and electronic levels.

Sialic acid

Sialic acids are a class of alpha-keto acid sugars with a nine-carbon backbone. The term "sialic acid" was first introduced by Swedish biochemist Gunnar Blix in 1952. The most common member of this group is N-acetylneuraminic acid found in animals and some prokaryotes.

Glycosaminoglycan Polysaccharides found in animal tissue

Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units. The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case of the sulfated glycosaminoglycan keratan, where, in place of the uronic sugar there is a galactose unit. GAGs are found in vertebrates, invertebrates and bacteria. Because GAGs are highly polar molecules and attract water; the body uses them as lubricants or shock absorbers.

The terms glycans and polysaccharides are defined by IUPAC as synonyms meaning "compounds consisting of a large number of monosaccharides linked glycosidically". However, in practice the term glycan may also be used to refer to the carbohydrate portion of a glycoconjugate, such as a glycoprotein, glycolipid, or a proteoglycan, even if the carbohydrate is only an oligosaccharide. Glycans usually consist solely of O-glycosidic linkages of monosaccharides. For example, cellulose is a glycan composed of β-1,4-linked D-glucose, and chitin is a glycan composed of β-1,4-linked N-acetyl-D-glucosamine. Glycans can be homo- or heteropolymers of monosaccharide residues, and can be linear or branched.

Pseudopeptidoglycan

Pseudopeptidoglycan is a major cell wall component of some Archaea that differs from bacterial peptidoglycan in chemical structure, but resembles bacterial peptidoglycan in function and physical structure. Pseudopeptidoglycan, in general, is only present in a few methanogenic archaea. The basic components are N-acetylglucosamine and N-acetyltalosaminuronic acid, which are linked by β-1,3-glycosidic bonds.

Heparan sulfate Linear polysaccharide in all animal tissues

Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins. It is in this form that HS binds to a variety of protein ligands, including Wnt, and regulates a wide range of biological activities, including developmental processes, angiogenesis, blood coagulation, abolishing detachment activity by GrB, and tumour metastasis. HS has also been shown to serve as cellular receptor for a number of viruses, including the respiratory syncytial virus. One study suggests that cellular heparan sulfate has a role in SARS-CoV-2 Infection, particularly when the virus attaches with ACE2.

Syndecan 1 Protein which in humans is encoded by the SDC1 gene

Syndecan 1 is a protein which in humans is encoded by the SDC1 gene. The protein is a transmembrane heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family. The syndecan-1 protein functions as an integral membrane protein and participates in cell proliferation, cell migration and cell-matrix interactions via its receptor for extracellular matrix proteins. Syndecan-1 is a sponge for growth factors and chemokines, with binding largely via heparan sulfate chains. The syndecans mediate cell binding, cell signaling, and cytoskeletal organization and syndecan receptors are required for internalization of the HIV-1 tat protein.

Syndecan

Syndecans are single transmembrane domain proteins that are thought to act as coreceptors, especially for G protein-coupled receptors. More specifically, these core proteins carry three to five heparan sulfate and chondroitin sulfate chains, i.e. they are proteoglycans, which allow for interaction with a large variety of ligands including fibroblast growth factors, vascular endothelial growth factor, transforming growth factor-beta, fibronectin and antithrombin-1. Interactions between fibronectin and some syndecans can be modulated by the extracellular matrix protein tenascin C.

Richard D. Cummings is an American biochemist who is the S. Daniel Abraham Professor of Surgery at Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, MA. He also the Chief of the Division of Surgical Sciences within the Department of Surgery. He is the Director of the Harvard Medical School Center for Glycoscience, Director of the National Center for Functional Glycomics, and also founder of the Glycomics Core at BIDMC. As of 2018 Cummings is also the Scientific Director of the Feihi Nutrition Laboratory at BIDMC. Before moving to BIDMC/HMS, Cummings was the William Patterson Timmie Professor and Chair of the Department of Biochemistry at Emory University School of Medicine in Atlanta, Georgia from 2006-2015. At Emory, Cummings was a founder in 2007 of the Emory Glycomics Center.

In enzymology, a [heparan sulfate]-glucosamine 3-sulfotransferase 1 is an enzyme that catalyzes the chemical reaction

NDST2

Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 2 is an enzyme that in humans is encoded by the NDST2 gene.

Ajit Varki is a physician-scientist who is distinguished professor of medicine and cellular and molecular medicine, co-director of the Glycobiology Research and Training Center at the University of California, San Diego (UCSD), and co-director of the UCSD/Salk Center for Academic Research and Training in Anthropogeny (CARTA). He is also executive editor of the textbook Essentials of Glycobiology and distinguished visiting professor at the Indian Institute of Technology in Madras and the National Center for Biological Sciences in Bangalore. He is a specialist advisor to the Human Gene Nomenclature Committee.

Carbohydrate sulfotransferase

Carbohydrate sulfotransferases are sulfotransferase enzymes that transfer sulfate to carbohydrate groups in glycoproteins and glycolipids. Carbohydrates are used by cells for a wide range of functions from structural purposes to extracellular communication. Carbohydrates are suitable for such a wide variety of functions due to the diversity in structure generated from monosaccharide composition, glycosidic linkage positions, chain branching, and covalent modification. Possible covalent modifications include acetylation, methylation, phosphorylation, and sulfation. Sulfation, performed by carbohydrate sulfotransferases, generates carbohydrate sulfate esters. These sulfate esters are only located extracellularly, whether through excretion into the extracellular matrix (ECM) or by presentation on the cell surface. As extracellular compounds, sulfated carbohydrates are mediators of intercellular communication, cellular adhesion, and ECM maintenance.

O-linked glycosylation is the attachment of a sugar molecule to the oxygen atom of serine (Ser) or threonine (Thr) residues in a protein. O-glycosylation is a post-translational modification that occurs after the protein has been synthesised. In eukaryotes, it occurs in the endoplasmic reticulum, Golgi apparatus and occasionally in the cytoplasm; in prokaryotes, it occurs in the cytoplasm. Several different sugars can be added to the serine or threonine, and they affect the protein in different ways by changing protein stability and regulating protein activity. O-glycans, which are the sugars added to the serine or threonine, have numerous functions throughout the body, including trafficking of cells in the immune system, allowing recognition of foreign material, controlling cell metabolism and providing cartilage and tendon flexibility. Because of the many functions they have, changes in O-glycosylation are important in many diseases including cancer, diabetes and Alzheimer's. O-glycosylation occurs in all domains of life, including eukaryotes, archaea and a number of pathogenic bacteria including Burkholderia cenocepacia, Neisseria gonorrhoeae and Acinetobacter baumannii.

Dally is the name of a gene that encodes a HS-modified-protein found in the fruit fly. The protein has to be processed after being codified, and in its mature form it is composed by 626 amino acids, forming a proteoglycan rich in heparin sulfate which is anchored to the cell surface via covalent linkage to glycophosphatidylinositol (GPI), so we can define it as a glypican. For its normal biosynthesis it requires sugarless (sgl), a gene that encodes an enzyme which plays a critical role in the process of modification of dally.

TEDC2

Tubulin epsilon and delta complex 2 (TEDC2), also known as Chromosome 16 open reading frame 59 (C16orf59), is a protein that in humans is encoded by the TEDC2 gene. Its NCBI accession number is NP_079384.2.

Rosalind Hauk Kornfeld (1935–2007) was a scientist at Washington University in St. Louis known for her research determining the structure and formation of oligosaccharides. The Society of Glycobiology annually awards a lifetime achievement award in her honor.

Nicki Packer FRSC is a Distinguished Professor of Glycoproteomics in the School of Natural Sciences at Macquarie University and Principal Research Leader at Griffith University's Institute for Glycomics. Packer is a Fellow of the Royal Society of Chemistry and in 2021 received the Distinguished Achievement in Proteomic Sciences Award from the Human Proteome Organization. Her research focuses on biological functional of glycoproteins by linking glycomics with proteomics and bioinformatics.

References

  1. ↑ http://cmm.ucsd.edu/
  2. ↑ http://grtc.ucsd.edu/
  3. 1 2 3 "Karl Meyer Lectureship Award Winners - 2007 - Jeffrey Esko". www.glycobiology.org. Archived from the original on 2013-09-28.
  4. ↑ "Stocks".
  5. 1 2 Varki A, Cummings RD, Esko JD, et al., editors. Essentials of Glycobiology. 2nd edition. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 2009. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1908/
  6. 1 2 McEntyre J, Lipman D. Foreword. In: Varki A, Cummings RD, Esko JD, et al., editors. Essentials of Glycobiology. 2nd edition. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 2009. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1918/
  7. ↑ Lin, Xinhua (2009). "An essential glycobiology resource for developmental biologists". Development. 136 (24): 4072–4073. doi:10.1242/dev.041194. S2CID   85245716.
  8. ↑ Esko, J.D.,Stewart, T.E., and Taylor, W.H. (1985) Animal cell mutants defective inglycosaminoglycan biosynthesis. Proc.Natl. Acad. Sci. USA 85:3197-3201. PMID   3858816
  9. ↑ Evolutionary differences in glycosaminoglycan fine structure detected by quantitative glycan reductive isotope labeling.Lawrence R, Olson SK, Steele RE, Wang L, Warrior R, Cummings RD, Esko JD.J Biol Chem. 2008 Nov 28;283(48):33674-84. PMID   18818196
  10. ↑ http://www.uu.se/nyheter/nyhet-visning/?id=784&area=1,2,3,4,7,16&typ=pm&na=&lang=sv [ dead link ]
  11. ↑ http://wals.od.nih.gov/
  12. ↑ "Archived copy" (PDF). Archived from the original (PDF) on 2014-04-02. Retrieved 2013-12-11.{{cite web}}: CS1 maint: archived copy as title (link)
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