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.
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.
|Rodriguez-Rivera, Frances P; Zhou, Xiaoxue; Theriot, Julie A et al. (2018) Acute Modulation of Mycobacterial Cell Envelope Biogenesis by Front-Line Tuberculosis Drugs. Angew Chem Int Ed Engl 57:5267-5272|
|Yang, Andrew C; du Bois, Haley; Olsson, Niclas et al. (2018) Multiple Click-Selective tRNA Synthetases Expand Mammalian Cell-Specific Proteomics. J Am Chem Soc 140:7046-7051|
|Wan, Stephanie J; Sullivan, Aaron B; Shieh, Peyton et al. (2018) IL-1R and MyD88 Contribute to the Absence of a Bacterial Microbiome on the Healthy Murine Cornea. Front Microbiol 9:1117|
|Tomlin, Frederick M; Gordon, Chelsea G; Han, Yisu et al. (2018) Site-specific incorporation of quadricyclane into a protein and photocleavage of the quadricyclane ligation adduct. Bioorg Med Chem 26:5280-5290|
|Keyser, Samantha G L; Utz, Ashley; Bertozzi, Carolyn R (2018) Computation-Guided Rational Design of a Peptide Motif That Reacts with Cyanobenzothiazoles via Internal Cysteine-Lysine Relay. J Org Chem 83:7467-7479|
|Jolly, Amber L; Agarwal, Paresh; Metruccio, Matteo M E et al. (2017) Corneal surface glycosylation is modulated by IL-1R and Pseudomonas aeruginosa challenge but is insufficient for inhibiting bacterial binding. FASEB J 31:2393-2404|
|Rodriguez-Rivera, Frances P; Zhou, Xiaoxue; Theriot, Julie A et al. (2017) Visualization of mycobacterial membrane dynamics in live cells. J Am Chem Soc 139:3488-3495|
|Ganesan, Lakshmi; Shieh, Peyton; Bertozzi, Carolyn R et al. (2017) Click-Chemistry Based High Throughput Screening Platform for Modulators of Ras Palmitoylation. Sci Rep 7:41147|
|Zhu, Xuejun; Shieh, Peyton; Su, Michael et al. (2016) A fluorogenic screening platform enables directed evolution of an alkyne biosynthetic tool. Chem Commun (Camb) 52:11239-42|
|Tsai, Cheng-Ting; Robinson, Peter V; Spencer, Carole A et al. (2016) Ultrasensitive Antibody Detection by Agglutination-PCR (ADAP). ACS Cent Sci 2:139-147|
Showing the most recent 10 out of 53 publications