# Disease and Race Specific Single-cell Epigenetic Mechanisms in Human SLE

> **NIH NIH R01** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2024 · $807,048

## Abstract

PROJECT SUMMARY
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by dysregulated
interferon responses and loss of self-tolerance to cellular antigens that result in inflammatory processes that
ultimately lead to systemic end-organ damage. Striking genetic and clinical differences exist between European
American (EA) and African American (AA) SLE patients that result in disparities in their diagnoses, management
and outcomes. Despite decades of research and over 100 risk loci identified, the underlying mechanisms driving
the pathogenesis of SLE and its racial disparities remain incompletely understood. Our lab has joined forces with
the team led by Jason Buenrostro, PhD, at Harvard to evaluate and understand how epigenetic regulation in
specific cell types contributes to both disease- and race-specific SLE pathogenesis. We use a sci-ATAC-seq
(single cell indexing assay for transposase-accessible chromatin), method developed and optimized in the
Buenrostro laboratory, to assess disease- and race-specific differences in genome-wide chromatin accessibility
(CA) in cell subtypes from cryopreserved peripheral blood mononuclear cells. Integrating these data with
genotyping data allows us to identify allelically imbalanced variants that are enriched in regions of CA (caQTLs),
suggesting a mechanistic role for these variants in regulating CA. Our preliminary data conducted in EA SLE
and healthy controls demonstrate that we are able to define multiple major PBMC cell subsets, and that extensive
differential CA and caQTLs discriminate between SLE case and control subjects. We now propose an expanded
study that will not only evaluate disease-specific CA and caQTL alterations in a much larger sample, but also
race-specific alterations. Integrating single-cell transcriptomic data and clinical data with CA and caQTL data
will facilitate the functional interpretation of SLE relevant CA differences. Our goals for this AR077434
resubmission are to 1) define cell type-specific differences in chromatin accessibility that identify both disease-
specific and race-specific alterations; 2) identify cell type and race-specific caQTLs that associate with
differences in CA between SLE cases and controls; and 3) define the mechanistic relationships between CA,
caQTLs, gene expression architectures, within the context of cis co-accessibility networks. We believe this
project positions us at the leading edge to develop a precise epigenetic roadmap connecting genetic variation to
deleterious cellular and clinical phenotypes that underlie the disease-specific mechanisms of SLE and its
remarkable race-specific disparities.

## Key facts

- **NIH application ID:** 10832501
- **Project number:** 5R01AI156724-04
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** Patrick M Gaffney
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $807,048
- **Award type:** 5
- **Project period:** 2021-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10832501

## Citation

> US National Institutes of Health, RePORTER application 10832501, Disease and Race Specific Single-cell Epigenetic Mechanisms in Human SLE (5R01AI156724-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10832501. Licensed CC0.

---

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