# Function and regulation of epithelial glycosylation

> **NIH NIH R35** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $525,698

## Abstract

Summary/abstract
This research program focuses on uncovering the biological roles of glycoconjugates. Part of this effort is
devoted to the development of chemical biology tools for glycoscience research. In the past, we have developed
photocrosslinking sugar analogs that can be incorporated into cellular glycoconjugates and used to covalently
crosslink glycoconjugates to their binding partners in a native context. These reagents can be used to identify
glycan-dependent binding interactions, and to characterize where and under what conditions that these
interactions occur. Over the next five years, we will further expand the scope of experiments that can be
performed by preparing additional photocrosslinking sugars, developing new methods for their incorporation,
and evaluating their incorporation into additional glycoconjugates. Using one of these photocrosslinking
sugars, we made the unexpected observation that cholera toxin can bind fucosylated glycoconjugates in
addition to its canonical receptor, the ganglioside GM1. Over the next five years, we will determine the
molecular structure of fucosylated glycoconjugates recognized by cholera toxin and characterize their role in
host cell intoxication. These studies are supported by our long-term collaboration with the Yrlid group
(University of Gothenburg) and their expertise in studying cholera disease mechanisms. Our studies of cholera
toxin receptors led us to become interested in the diverse glycoconjugates that line the intestinal and
respiratory epithelia. A CRISPR screen designed to identify genes that modulate cholera toxin binding to cell
surfaces identified a number of candidate genes that may function in the regulation of glycosylation by diverse
mechanisms. Over the next five years, we will characterize novel regulators of glycosylation and determine how
they shape the glycome, modulating glycan features such as polyLacNAc chain length and the degree of
fucosylation. The long-term goal of these studies is to determine how glycan features vary among individuals,
their association with disease states, and their impact on host-microbe interactions.

## Key facts

- **NIH application ID:** 10839977
- **Project number:** 5R35GM145599-03
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Jennifer J Kohler
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $525,698
- **Award type:** 5
- **Project period:** 2022-06-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10839977

## Citation

> US National Institutes of Health, RePORTER application 10839977, Function and regulation of epithelial glycosylation (5R35GM145599-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10839977. Licensed CC0.

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