# Project 2: The Isoform repertoire and epigenome of Pediatric SLE

> **NIH NIH P50** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $644,556

## Abstract

PROJECT SUMMARY 
SLE is a disease of high morbidity for which treatment options are poor. Identifying relevant targets for 
therapeutic intervention is difficult owing to the molecular and clinical heterogeneity of the disease. Through a 
large body of work, we have demonstrated that blood-based transcriptomic profiling can be used to parse out 
distinct transcriptional differences in immune function in health and disease. Relevant to the current application 
are our studies showing that SLE can be divided into seven disease subgroups based on distinct blood 
transcriptional signatures. More recently, we developed a sophisticated for integrated Profiling and Analysis 
Pipeline (iPAP) that we used to identify meaningful epigenetic and transcriptomic differences in human 
populations, including SLE cohorts. Building upon this knowledgebase will help us identify potential drivers of 
the disease, and ultimately novel biomarkers and novel therapeutic targets for SLE. We hypothesize that SLE 
is comprised of a spectrum of disease subtypes that can be categorized according to mutually distinct 
epigenomic, isoformic and transcriptomic features. The goal of this project is to characterize the repertoire 
of immune cell isoforms and the epigenome profiles associated with three of the seven most frequent 
pediatric SLE subgroups: SLE-Plasmablast (SLE-P), characterized by a plasmablast transcriptional signature 
and the presence of increased circulating plasmablasts; SLE-Interferon/Myeloid cells (SLE-IM), which shows 
an IFN and a neutrophil signature; and SLE-Plasmablast/ Interferon/Myeloid cells (SLE-PIM) displaying the 
three main signatures. We will use novel experimental paradigms that incorporate cutting-edge genomic 
technologies and build upon our established expertise in molecular immune profiling. Our project contains two 
Specific Aims: 1) To analyze the alternatively spliced transcriptome of blood cells from the three SLE 
patient subgroups, in which we will apply both short-read (Illumina HiSeq2500) and long-read (PacBio RSII) 
sequencing technologies to interrogate the isoform repertoire of PBMCs and select immune cell subsets; and 
2) To determine the epigenome of blood cells from the three SLE subgroups, through studies capitalizing 
on a robust and sensitive new epigenomic assay called ATAC-seq coupled to Methyl-seq. Healthy age- 
matched samples will be used as controls in all experiments and, we will also examine samples from children 
with active juvenile dermatomyositis and systemic juvenile arthritis (n=5 per group), to identify those isoforms 
and signatures unique to SLE from those more generally associated with autoimmunity. Our team includes 
experts in immunology, genomics, epigenetics, systems biology of disease, computational biology, data 
management and statistics, who bring the collective expertise necessary for generating top quality genomics 
data and for robust data analysis using state-of-the-art methods. We will also cr...

## Key facts

- **NIH application ID:** 9891961
- **Project number:** 5P50AR070594-04
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Jacques F Banchereau
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $644,556
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891961

## Citation

> US National Institutes of Health, RePORTER application 9891961, Project 2: The Isoform repertoire and epigenome of Pediatric SLE (5P50AR070594-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9891961. Licensed CC0.

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