# Multi-Omic Characterization of Immune Cells in Sarcoidosis

> **NIH NIH R21** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2024 · $127,875

## Abstract

ABSTRACT
Sarcoidosis is a systemic granulomatous disease with striking heterogeneity of clinical course and increasing
mortality and morbidity rates. Diagnosis is difficult and predicting disease outcomes is virtually impossible.
While it is known that sarcoidosis likely involves host genetic susceptibility and a dysregulated immune
response to any number of environmental factors, the mechanisms by which granulomas form and the
determinants of severity and disease manifestations remain elusive. Our team has been at the forefront of
genetics and transcriptomics in sarcoidosis, including the identification of genes for susceptibility, severity,
ancestry- and organ-specific effects, the first and only single-cell RNA sequencing study of sarcoidosis and the
first GWAS of pulmonary fibrosis in patients of African ancestry (AA). These findings provide the foundation for
further dissection of cellular mechanisms that lead to systemic immune dysregulation and tissue-specific
inflammatory response. Our current proposal will advance the field by filling critical gaps in sarcoidosis
research, including the lack of biomarkers for sarcoidosis diagnosis and prognosis, and the absence
of mechanistic connections between genetics, genomics, and immune profiles, in the periphery and
affected organs. We will exploit the immunological, genomic, and bioinformatic expertise of our team to apply
an innovative, iterative, and integrative multi-omic approach to discover molecular signatures characterizing
sarcoidosis and its disease burden. Specifically, in Aim 1, we will use circulating protein levels from over 200
sarcoidosis patients of AA and European ancestry (EA) and 200 controls to a) develop predictive models of
sarcoidosis susceptibility and disease burden via a novel application of machine learning, and b) define unique
immune cell subsets based on cell-specific expression of cytokines of interest, and thus identify novel
candidate genes and pathways. In Aim 2, we will identify candidate genes that are best suited for functional
and drug target studies based on integrating the data collected across multiple biological systems (including
genetic, transcriptomics, and proteomics), from multiple sample sources (including circulating immune cells
and brochoalveolar lavage). Our work will be greatly facilitated by the extensive genetic, genomic, and clinical
data available to us from our own cohorts (>2,900 EA and >3,000 AA) and the TOPMed Consortium (of which
we are members). This application includes a novel approach to integrating data across multiple biological
systems, with strong preliminary data to support the rigor and success of our proposal.

## Key facts

- **NIH application ID:** 10954075
- **Project number:** 1R21HL175092-01
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** Courtney Montgomery
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $127,875
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10954075

## Citation

> US National Institutes of Health, RePORTER application 10954075, Multi-Omic Characterization of Immune Cells in Sarcoidosis (1R21HL175092-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10954075. Licensed CC0.

---

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