Research

Glycan synthesis follows highly interconnected paths within a cell, and modulation of a single step can drastically alter the cellular glycome. This modulation occurs not just through the activity and localization of known biosynthetic enzymes but also the availability of sugar nucleotides, the trafficking of substrates, and the organization of cellular organelles. Together, the cell uses this complex functional network to regulate the glycome both during homeostasis and in response to perturbations such as cellular stress. Our lab aims to uncover the identity and organization of the genes that make up this largely unknown “expanded” network of glyco-regulation using functional genomics and systems biology. Through uncovering these genetic regulatory networks, our long-term goal is to comprehensively understand glycosylation regulation in health and disease states.

The diverse array of cell surface glycans and the information they present are primarily interpreted by glycan-binding proteins called lectins. The endogenous glycan ligands of many human lectins, especially in the cellular context, remain unknown. A key goal of my group is to systematically define the precise binding specificity of human lectins on endogenous glycan motifs using CRISPR screening and glycomics approaches. This work will uncover the functionally significant glycan motifs that not only include the “natural” ligands essential for homeostasis but also “off-target” ligands that are present in disease states that may contribute to pathological conditions. We will characterize how interactions between lectins and their different glycan ligands lead to different functional signaling outcomes.