# Translational Center of Molecular Profiling in Preclinical and Established Lupus (COMPEL)

> **NIH NIH P50** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $1,297,885

## Abstract

NYU School of Medicine and collaborating clinical and basic investigators in Medicine and Pathology propose
to establish the Translational Center of Molecular Profiling in Preclinical and Established Lupus (COMPEL)
comprising 3 Projects, 2 Research Cores, and an Administrative Core. The overarching goal is to elucidate the
mechanisms by which Systemic Lupus Erythematosus (SLE), a prototypic yet clinically and immuno-
molecularly heterogeneous autoimmune disease, is initiated and perpetuated. COMPEL leverages a) a unique
cohort of asymptomatic women presenting with breakdown in B cell tolerance identified because of neonatal
lupus (NL) in an offspring (Research Registry for Neonatal Lupus, RRNL) and b) a robustly phenotyped cohort
of established SLE patients spanning diverse racial backgrounds and with a high penetrance of serious illness
(NYU Cohort). Project 1 profiles anti-Ro preclinical and clinical autoimmunity to identify blueprints of an
immune system that remains preclinical, and in individuals who have progressed to overt disease. The
approach rests on identifying associations between host genetics, the microbiome, and the phenotype of CD4+
T cells, which constitute an immune triumvirate of T cells, antigen-presenting cells with an MHC II-defined
specificity towards particular microbial taxa, and B cells. Project 2 explores microbiome pathobionts and SLE
pathogenesis to understand how specific candidate pathobiont bacterial isolates contribute to overt SLE
disease and flares, and to peripheral blood expansion of disease-associated B cell clones. Human intestinal
IgA responses can be both specific for in vivo eliciting bacteria, and often cross-reactive with self-antigens. Yet,
the gut-associated B cell response has not been investigated in SLE as a driver of autoimmune disease.
Project 3 focuses on DNASE1L3, a unique secreted DNase that is essential for protection against SLE. We
have shown that DNASE1L3 digests DNA in circulating microparticles and antibody (Ab) reactivity to
microparticle antigens is frequently detected in SLE. The project will explore Ab responses to DNASE1L3-
sensitive microparticle antigens in preclinical and established SLE patients; molecularly characterize these
antigens and test DNASE1L3 as a therapeutic. The Research Technology Core brings advanced technology
for NGS applications of large scale autoAb gene repertoire analyses from human B cell samples and will sort
intestinal IgA-coated bacteria profiled by 16S rRNA microbiome surveys. The Clinical Core comprises the
database (REDCap) and biobank (Freezerworks) of 3 cohorts (RRNL, NYU Lupus Cohort, healthy controls) to
facilitate translational studies. The Administrative Core supports organizational, financial and reporting
activities. The analytic team brings expertise in biostatics, genetic statistics, bioinformatics and computational
science. External advisors covering translational SLE, the microbiome, T cell biology and mucosal immunity,
and 2 lay persons w...

## Key facts

- **NIH application ID:** 10249207
- **Project number:** 5P50AR070591-05
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Jill P Buyon
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,297,885
- **Award type:** 5
- **Project period:** 2017-09-22 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10249207

## Citation

> US National Institutes of Health, RePORTER application 10249207, Translational Center of Molecular Profiling in Preclinical and Established Lupus (COMPEL) (5P50AR070591-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10249207. Licensed CC0.

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