We are primarily a genetics lab using genomic technologies to understand autoimmune, fibrotic, and health disparity conditions. We have taken a comprehensive approach toward identifying both common and rare variants associated with disease susceptibility.

To identify common variants, we perform SNP microarray genotyping and imputation for fine-mapping, followed by a genome-wide association study (GWAS) to identify disease-associated genetic variants. To identify rare variants, we utilize high-throughput DNA sequencing platforms for whole genome or whole exome sequencing followed by variant annotation and scoring to prioritize causal variants. We also use gene mapping tools to identify genetic loci associated with traits in recently admixed populations (admixture mapping).

Another goal of our lab is to understand transcriptional regulation of these disease-associated genes using cutting-edge technologies, including RNA-seq, eQTL, Hi-C, ATAC-seq, ChIP-seq, CUT&RUN, CRISPR-Cas9 genetic screens, and bioinformatics.

Focus Areas

Scleroderma

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Scleroderma (systemic sclerosis) is a chronic, multi-system, autoimmune disease characterized by progressive fibrosis of the skin and internal organs. There is a health disparity in African Americans, who have an increased prevalence of scleroderma compared to European Americans.

We have established the Genome Research in African American Scleroderma Patients (GRASP) consortium. It is comprised of 25 centers across the United States. Our goal is to enroll African American scleroderma patients and perform admixture mapping to identify ancestry-specific variants contributing to increased disease risk in this population.

Autoimmunity

Antibodies directed towards self-antigens are a hallmark of autoimmune diseases. We are interested in understanding the timing and development of autoantibodies in the pre-clinical phase of autoimmune diseases. Human leukocyte antigen (HLA) genes have the strongest influence on autoimmune disease susceptibility and these HLA alleles encode variations in the antigen-binding grooves of the HLA molecules that determine their binding affinity for specific antigens presented to T cells. T cells recognize these peptide-HLA complexes by the T cell receptor (TCR), located on the surface of T cells. We are using next generation sequencing technologies to analyze the extreme diversity of the TCR repertoire. Elucidating the role of the HLA molecules in antigen recognition, peptide presentation and autoimmunity induction is an important area of focus. We are also exploring the link between HLA alleles, autoantibodies, and environmental triggers in the pathogenesis of autoimmune diseases.

The Regulome Project

The NIH Regulome Project was established in 2010 as an ongoing collaboration of intramural and invited extramural research groups.

Its primary goal is to understand transcriptional regulation in mammalian systems using cutting-edge technologies, including Hi-C and derivatives, single-molecule microscopy, real-time transcriptional assays, cryo-EM, genomics, biological modeling, CRISPR-Cas9 genetic screens, neural networks, and biophysics.

Core Research Facilities

Labs at the NIAMS are supported by the following state-of-the-art facilities and services:

• Biodata Mining and Discovery
• Flow Cytometry
• Genomic Technology
• Laboratory Animal Care and Use
• Light Imaging
• Translational Immunology