# Core C: Subtractive Single Nucleus Seq and Spatial Multi-omics Core

> **NIH NIH P01** · YALE UNIVERSITY · 2024 · $293,125

## Abstract

PROJECT SUMMARY – CORE C
Efficient and reproducible detection of immune cell states is paramount to our understanding of the immune
responses in the context of health and disease, such as cancer and autoimmunity. Immune function is
highly dependent upon costimulatory signals where their role has become apparent in the study of tumor
infiltrating lymphocytes with PD-1/PD-L1 expression, as well as in autoimmune disease particularly with
activation of autoreactive T cells and costimulatory receptor CD226 and its ligand CD155 which is shared
with TIGIT. Achieving a mechanistic understanding by which PD-1/PD-L1 and TIGIT/CD155 axes regulate T
cell and myeloid cell function will enable refinement of the therapeutic use and target of these costimulatory
pathways. The Single Cell and Spatial Multi-omics Core (Core C) at Yale University will provide support for novel
transcriptional, epigenetic, and spatial profiling of single cells as well as enriched immune cell types across all
three projects of the Program Project Grant. Our core has established systematic pipelines for processing single
cell RNA-seq and ATAC-seq from low-input samples, from single cells or single nuclei, as well as for spatial
transcriptomics using DBiT-seq, a single cell spatial technology newly developed at Yale which will be used in
both experimental models and in human tissues across the three projects. This core provides capabilities and a
pipeline for the preparation, sequencing and single cell analysis and data integration across species. Our
experimental and computational resource will facilitate (1) the investigations of immunity in mouse models that
are deficient for TIGIT, PD1, or both, (2) the characterization of cells or nuclei or sections human tissues from
patients with multiple sclerosis and glioblastoma, and (3) the single cell, integrative analysis of all data generated
in Projects 1-3. Overall, the outcome will be a better understanding of co-stimulatory and co-inhibitory
mechanisms, and its function in regulating inflammasome activation in T cells and myeloid cells in human
diseases and disease models. This may potentially lead to new avenues for therapy for autoimmunity and
cancer.

## Key facts

- **NIH application ID:** 10839298
- **Project number:** 5P01AI039671-26
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Le Zhang
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $293,125
- **Award type:** 5
- **Project period:** 1997-09-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10839298

## Citation

> US National Institutes of Health, RePORTER application 10839298, Core C: Subtractive Single Nucleus Seq and Spatial Multi-omics Core (5P01AI039671-26). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10839298. Licensed CC0.

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