Adeline Schmidt

Adeline Schmidt

Biography

Adeline Schmidt is a rising junior at the University of Florida, majoring in Chemical
Engineering with a Biomolecular Engineering minor. Driven by a fascination with molecular
mechanisms, she conducts undergraduate research in the Denard Group, utilizing a yeast surface
display platform to identify inhibitors for SARS-CoV-2 variants. Previously, in the Rinaldi-
Ramos Lab, she focused on encapsulating superparamagnetic iron oxide nanoparticles in a PEG
polymer matrix. By minimizing Brownian relaxation to enable rapid magnetic responses for
higher-resolution imaging, this experience in microfluidics sparked her passion for programmable
polymers. Specifically, she is interested in cross-linking substrates into microgel matrices for
enzyme-triggered, site-specific drug delivery traceable via magnetic particle imaging.

Computational Validation of the CD44/Siglec-9 Glyco-Immune Checkpoint in
Various Human Cancers
Adeline O. Schmidt1, Tran Luu2,3, Jessica C. Stark2,3,4
1Department of Chemical Engineering, University of Florida
2Department of Biological Engineering, Massachusetts Institute of Technology
3Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
4Department of Chemical Engineering, Massachusetts Institute of Technology

Immune checkpoint blockades have advanced cancer treatment. However, many patients
remain unresponsive, motivating a need to identify other pathways that contribute to resistance.
Siglec-9, a glycan-binding immune receptor, has emerged as a glyco-immune checkpoint
that suppresses antitumor immunity in multiple cancers. The Stark lab recently discovered
CD44 as a high-affinity and cancer-associated ligand for Siglec-9 that dampens macrophage
phagocytosis, highlighting the CD44/Siglec-9 axis as a promising myeloid checkpoint target.
Because direct studies of Siglec-9 interactions in humans are limited, further validation using
human datasets is needed. To address this, we analyzed published scRNA-seq and spatial
transcriptomic data of breast, renal, and colorectal cancers. We used ST3GAL4, a key enzyme
mediating Siglec-9 ligand synthesis, as a proxy for the Siglec-9-binding glycoform of CD44.
In three cancers, scRNA-seq shows CD44/ST3GAL4 co-expression in epithelial and stromal
tumor cells, and SIGLEC9 concentrated in myeloid cells. In colorectal and breast cancers,
CD44/ST3GAL4 co-expression is higher in tumor than matched normal epithelium, and
myeloid SIGLEC9 is increased in cancer. Interestingly, patients with higher myeloid SIGLEC9
also show higher epithelial CD44/ST3GAL4 co-expression. Spatial transcriptomics confirmed
the tumor-enriched CD44 expression in colorectal cancer. Our analyses support CD44/Siglec-9
as a cancer-associated glyco-immune axis across human cancers.