Carolyn R. Bertozzi
Investigator, Howard Hughes Medical Institute; Professor of Biochemistry & Molecular Biology and Chemistry, University of California, Berkeley, USA
Chemistry in Living Systems: Shedding Light on Glycans
Amajority of cell surface and secreted proteins are posttranslationally modified by the addition of glycans. These complex structures can provide information regarding the state of health of cells or organisms. Indeed, changes in the structures of protein- and cell surface-associated glycans are a hallmark of many cancers, chronically inflamed tissues, and microbial infections. The ability to probe glycosylation in living systems may therefore reveal new biomarkers of disease and provide new avenues for diagnostic imaging. We are developing chemical technologies for visualizing glycans in living systems. As products of secondary metabolism, glycans are constructed from simple monosaccharide precursors. We exploit these metabolic pathways to incorporate bioorthogonal chemical reporters into glycans. The chemical reporters comprise small functional groups, such as the azide, that can be detected by covalent reaction with highly selective probes. New chemical reactions have been developed for this purpose, such as the Staudinger ligation with phosphines and strain-promoted [3+2] cycloaddition with functionalized cyclooctynes. Applications of the technique to the identification of cancer-associated glycan biomarkers and noninvasive imaging of glycosylation changes in animals disease models are currently being pursued.Bertozzi earned her Ph.D. at University of California, Berkeley in 1993, working on the chemical synthesis of oligosaccharide derivatives. After accomplishing postdoctoral work at UCSF in the field of cellular immunology, she joined the UC Berkeley faculty in 1996 and received a promotion to associate professor and professor in 1999, 2002, respectively.
Bertozzi’s research interests are studying cell surface interactions that contribute to human health and disease with specific projects in the areas of cancer, inflammation and bacterial infection. Working with reengineering cell surfaces to controlling cells' social interactions, she and her coworkers developed a key chemical reaction, modified Staudinger reaction, that adds a marker molecule to cell surface sugars, and they later refined the technique for use in living animals. The particular sugars they targeted are produced in elevated amounts by cancer cells and by inflamed cells. This pioneering approach uses laboratory-developed reagents that do not react with the normal molecules in the body, only with each other, and thus do not interfere with the sugars' ability to carry out their normal signaling functions. Eventually, her innovative approach may allow investigators to target cancer cells for diagnosis and treatment or to design cells to join artificial materials that are used in medical implants. During this same period, she is studying biological sulfation pathways that serve a regulatory during an inflammatory response in humans and during mycobacterial infection. Using genomics approaches, Bertozzi and coworkers have identified genes encoding sulfating enzymes that contribute to inflammation, tumor metastasis and possibly microbial infection. Very recently, they have been exploring new methods for the synthesis of homogeneous glycoproteins and their mimetics. She has published over 180 research papers, patents and one book.
Awards and Honorary Societies
Bertozzi has received the Ernst Schering Prize (2007); T.Z. and Irmgard Chu Distinguished Professorship in Chemistry (2005); Havinga Medal, Univ. Leiden (2005); Iota Sigma Pi Agnes Fay Morgan Research Award (2004); Irving Sigal Young Investigator Award of the Protein Society (2002); Donald Sterling Noyce Prize for Excellence in Undergraduate Teaching (2001); UC Berkeley Distinguished Teaching Award (2001); ACS Award in Pure Chemistry (2001); Merck Academic Development Program Award (2000); UC Berkeley Department of Chemistry Teaching Award (2000); Presidential Early Career Award in Science and Engineering (PECASE) (2000); MacArthur Foundation Award (1999); Camille Dreyfus Teacher-Scholar Award (1999); Arthur C. Cope Scholar Award (ACS) (1999); Joel H. Hildebrand Chair in Chemistry (1998-2000); Beckman Young Investigator Award (1998); Prytanean Faculty Award (1998); Glaxo Wellcome Scholar (1998); Research Corporation Research Innovation Award (1998); Office of Naval Research Young Investigator Award (1998); Horace S. Isbell Award in Carbohydrate Chemistry (ACS) (1997); Alfred P. Sloan Research Fellow (1997); Burroughs Wellcome New Investigator Award in Pharmacology (1997); Pew Scholars Award in the Biomedical Sciences (1996); Exxon Education Fund Young Investigator Award (1996). She is an elected member of the National Academy of Sciences (2005); the American Academy of Arts and Sciences (2003); and the American Association for the Advancement of Science (2002).