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SUMMARY:Explorations of N- and O-linked Glycosylation  on Extracellular an
 d Intracellular Cell Surfaces - Prof. Catherine Costello\; William Fairfie
 ld Warren Distinguished Professor and Director of the Center for Biomedica
 l Mass Spectrometry\, Boston University\, Boston\, MA
DTSTART:20200923T140000Z
DTEND:20200923T150000Z
UID:TALK150229@talks.cam.ac.uk
CONTACT:Bobbie Claxton
DESCRIPTION:N- and O-linked glycosylation is often the key to inter- and i
 ntracellular signaling\, as well as the entry of pathogens and toxins. Mas
 s spectrometry and complementary approaches are powerful tools for the det
 ermination of the locations and specificity of such interactions. This can
  help to understand normal and aberrant pathways\, and guide development o
 f therapeutic interventions. Representative examples\, including the follo
 wing\, will be discussed.\n\nMutation of one N-glycosylation site near the
  Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) ligand binding si
 te quickly amplified its ligand-dependent phosphorylation (activation) at 
 specific sites\, and resulted in higher levels of phospho-Src compared to 
 wild type VEGFR-2\, which may have implications for endothelial cell proli
 feration and migration\, whereas mutations at nearby N-glycosylation sites
  did not appear to impact ligand-mediated activation of VEGFR-2.\n\nAt spe
 cific N-glycosylation sites\, Epidermal Growth Factor Receptor (EGFR) from
  indolent CAL27 cells had highly fucosylated N-glycans\, whereas the corre
 sponding N-linked glycans on EGFR from metastatic HSC-3 cells displayed mu
 ch lower levels of fucosylation. Our MS/MS data showed that treatment with
  a drug candidate promoted modification of HSC-3 glycans with terminal fuc
 ose\, potentially inhibiting EGFR signaling. The results suggest inhibitio
 n of β-catenin/CBP signaling as a therapeutic approach to downregulate EG
 FR pro-tumorigenic activity. \n\nSurprising results obtained during recent
  studies revealed that highly fucosylated proteins are present adjacent to
  the nucleus of cells in the pathogens Cryptosporidium and T. gondii and r
 elated organisms. These unusual protein modifications\, which apparently a
 rose via the kidnapping of plant genes\, may represent targets for drug de
 velopment. \n\nAbout the speaker:\n\nCatherine E. Costello is a William Fa
 irfield Warren Distinguished Professor at Boston University\, with appoint
 ments in the Depts. of Biochemistry\, Physiology & Biophysics\, and Chemis
 try. She earned her AB at Emmanuel College\, Boston\, and PhD at Georgetow
 n University\, Washington\, DC\, and was a postdoctoral fellow and Senior 
 Research Scientist at MIT. She founded the BU School of Medicine Center fo
 r Biomedical Mass Spectrometry in 1994. Her research centers on developmen
 t of MS-based methods for biopolymers and their application to study glyco
 biology\, protein post-translational modifications\, protein misfolding di
 sorders\, cardiovascular and infectious diseases\, and bioactive lipids. S
 he has authored nearly 400 research papers. She was President of the Ameri
 can Society for Mass Spectrometry from 2002-2004 and the International Hum
 an Proteome Organization in 2011 & 2012\, and the International Mass Spect
 rometry Foundation from 2014-2018. She has received several major national
  and international recognitions in the fields of MS\, glycobiology\, prote
 omics and chemistry and is a Fellow of the ACS and the AAAS.\n\n\n\n\nJoin
  Zoom here:\nhttps://zoom.us/j/96361687266?pwd=OENwLzN2R3JLWk8zb3QxRDZOemZ
 nQT09 \n\nMeeting ID:        963 6168 7266\nPasscode:          149323
LOCATION:Online via zoom
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