# Single Cell Analysis and Immunogenetics

> **NIH NIH P01** · DANA-FARBER CANCER INST · 2024 · $282,553

## Abstract

Project Summary
The projects proposed for this grant application seek to characterize response and resistance to treatments for
chronic graft versus host disease (cGVHD) following hematopoietic stem cell transplantation (HCT). Core 1 will
support the single cell- and immunogenomics-related goals of these projects by focusing on applying the latest
experimental and computational tools to these studies. Bulk and single-cell transcriptome sequencing of immune
and lung cell populations (Aim 1) will be used to identify relevant pathways related to response to treatment of
cGVHD, to identify transcriptional aspects of the metabolic signature elucidated in mouse lung cGVHD models,
and to characterize the lung pathogenesis and immune response related to Bronchiolitis Obliterans Syndrome
(BOS) following HCT. Response of T cells to cGVHD treatments and to BOS will be further characterized by
TCR repertoire analysis using targeted bulk and single-cell sequencing to assess T cell clonality (Aim 2). Core
1 will analyze whole exome sequencing data from donor and recipient DNA to identify polymorphic differences
between donor and recipient, and use tissue expression databases to determine which of these variants are
expressed in lung. Recently developed sophisticated algorithms will be implemented to use this information to
predict personal HLA-binding peptides that comprise minor histocompatibility antigens (Aim 3). The paired
alpha/beta TCR chain single-cell sequence information will be used to reconstruct cell lines expressing individual
enriched TCRs (Aim 4) in order to functionally determine exactly which TCR interacts with which antigen. This
analysis will directly assess if mHAg-directed T cell responses contribute to clinical responses to therapy.

## Key facts

- **NIH application ID:** 10914134
- **Project number:** 5P01HL158505-03
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Kenneth James Livak
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $282,553
- **Award type:** 5
- **Project period:** 2022-09-15 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10914134

## Citation

> US National Institutes of Health, RePORTER application 10914134, Single Cell Analysis and Immunogenetics (5P01HL158505-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10914134. Licensed CC0.

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