The broad objective of this project is to apply a technique developed in our lab termed metabolic oligosaccharide engineering to in vivo imaging of global changes in the glycome associated with embryonic development and cancer. The glycome is the totality of glycans that cells produce under specified conditions of time, space and environment. Changes in the glycome's composition and distribution are associated with embryogenesis and cancer progression. We seek to develop chemical tools for imaging the dynamic cell-surface glycome in living organisms. We plan to pursue five specific aims that further expand the scope of the glycan imaging technology and apply our methods to new avenues of biological investigation.
Aim 1 builds directly from our ongoing work in zebrafish imaging, with a shift in focus to disease models in this organism.
Aim 2 seeks to expand the glycan imaging technique to bacterial systems, with an eye for monitoring changes in outer membrane glycolipids and capsular polysaccharides that might correlate with pathogenesis.
Aim 3 focuses on the , development of probes for imaging glycans in mouse tumor models, building from our earlier work in this model organism.
Aim 4 seeks to build the bioorthogonal reaction compendium with second-generation quadricyclane ligation chemistries as well as new reactions based on phosphinoboranes.

Public Health Relevance

The goal of this project is to develop tools from the field of chemistry that can help researchers and. physicians monitor the changes in cell-surface glycans inside the body using imaging techniques. These chemical tools could be useful for cancer detection and diagnosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37GM058867-21
Application #
9276033
Study Section
Special Emphasis Panel (NSS)
Program Officer
Marino, Pamela
Project Start
1999-01-01
Project End
2019-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
21
Fiscal Year
2017
Total Cost
$493,976
Indirect Cost
$179,824
Name
Stanford University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304
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