# Single Cell and Immunogenomics

> **NIH NIH P01** · DANA-FARBER CANCER INST · 2022 · $282,594

## Abstract

Project Summary
The projects proposed for this grant application seek to test novel transplant (HCT)-based immunomodulatory
combination treatments for AML and MDS, to dissect how leukemia cells and their surrounding immune cell
populations co-evolve in relationship to allo-HCT course (with the aim of gaining essential insights into the
rational design of effective combination therapy for AML and MDS), and to understand how donor clonal
hematopoiesis (CHIP) in the stem cell population impacts the reconstitution of immune cell subpopulations. Core
3 will support the single cell- and immunogenomics-related goals of these projects by focusing on applying the
latest computational and experimental tools to these studies. Core 3 will analyze whole exome sequencing data
from leukemia and normal samples to identify cancer-specific somatic mutations and polymorphic differences
between donor and recipient, and use matched RNA sequencing data to determine which of these variants are
expressed. Recently developed sophisticated algorithms will be implemented to use this information to predict
personal HLA-binding peptides that compose personal leukemia neoantigens and hematopoietic-lineage
restricted minor histocompatibility antigens (Aim 1). In order to determine the immune response to HCT, single-
cell transcriptome sequencing of non-tumor immune cell populations will be used to identify pathways related to
immune cell functions (Aim 2). Targeted RNA analysis will be used to determine how these discovered
phenotypes relate to the genotype of individual cells and will be used to define how CHIP affects response to
HCT. Response of T cells to HCT will be further characterized by TCR repertoire analysis using targeted bulk
and single-cell sequencing to assess T cell clonality (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
neoantigen- or mHAg-directed T cell responses contribute to clinical responses to therapy.

## Key facts

- **NIH application ID:** 10465100
- **Project number:** 5P01CA229092-04
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Kenneth James Livak
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $282,594
- **Award type:** 5
- **Project period:** 2019-08-14 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465100

## Citation

> US National Institutes of Health, RePORTER application 10465100, Single Cell and Immunogenomics (5P01CA229092-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10465100. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*