Professor Carolyn Bertozzi, Stanford University

"Why Do Cancer Cells Have Altered Glycosylation?"

About the Seminar:

While altered glycosylation patterns have long been identified as hallmarks of cancer, their functional significance with respect to tumor progression are not well understood. Two examples are overexpression of mucin glycoproteins (densely glycosylated cell-surface molecules with unusual physical properties) and hypermodification of glycoproteins with the terminal sugar sialic acid. These glycosylation phenotypes are found on numerous cancer types with highly varied underlying driver mutations and their magnitude tends to correlate with tumor aggressiveness. To test hypotheses regarding the functional significance of cancerglycomes, we developed an approach to engineer the cell surface “glycocalyx” with chemically defined glycopolymers that emulate cancer-associated structures. Using living polymerization and chemoselective ligation chemistries, we synthesize glycopolymers functionalized with a biophysical probe on one end and a lipid capable of membrane insertion on the other. These biomimetic structures can be displayed on live cell membranes where they acquire functions analogous to natural mucin glycoproteins. Our work using this platform suggests that hypersialylation protects tumor cells from innate immune surveillance, whereas mucin upregulation alters the physical properties of the glycocalyx so as to promote focal adhesion formation and signaling.  Both glycophenotypes can thus be understood as evolutionary adaptations of cancer cells under various selective pressures.

About the Speaker:

Carolyn Bertozzi is the Anne T. and Robert M. Bass Professor of Chemistry and Professor of Chemical & Systems Biology and Radiology (by courtesy) at Stanford University, and an Investigator of the Howard Hughes Medical Institute.  She completed her undergraduate degree in Chemistry from Harvard University in 1988 and her Ph.D. in Chemistry from UC Berkeley in 1993. After completing postdoctoral work at UCSF in the field of cellular immunology, she joined the UC Berkeley faculty in 1996.  In June 2015, she joined the faculty at Stanford University coincident with the launch of Stanford's ChEM-H institute.

Prof. Bertozzi's research interests span the disciplines of chemistry and biology with an emphasis on studies of cell surface glycosylation pertinent to disease states.  Her lab focuses on profiling changes in cell surface glycosylation associated with cancer, inflammation and bacterial infection, and exploiting this information for development of diagnostic and therapeutic approaches, most recently in the area of immuno-oncology.  She has been recognized with many honors and awards for her research accomplishments.  She is an elected member of the Institute of Medicine, National Academy of Sciences, and American Academy of Arts and Sciences. She has been awarded the Lemelson-MIT Prize, the Heinrich Wieland Prize, and a MacArthur Foundation Fellowship, among many others.