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## Overview

#### Assistant Clinical Investigator

Pravitt Gourh, M.D. 

pravitt.gourh@nih.gov

#### Research Areas (IRP Lab Groups)

Autoimmunity

Clinical Research

Computational Biology

Genetics and Genomics

Health Disparities

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

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

## Staff

**Pravitt Gourh, M.D. **

pravitt.gourh@nih.gov

**Cindy Beharry, M.S.**

cindy.beharry@nih.gov

**Kaavya Gudapati, B.S.**

gudapatik2@nih.gov

**Jordan Hicks, B.S.**

jordan.hicks@nih.gov

**Urvashi Kaundal, Ph.D.**

fnu.urvashi@nih.gov

**Yosuke Kunishita, M.D., Ph.D.**

yosuke.kunishita@nih.gov

**Devin Teehan, B.S.**

devin.teehan@nih.gov

*‌ *

Our lab is always seeking to attract diverse and talented candidates. If you are interested in joining our team, please contact us.

## Former Lab Members

Emilee Stenson, Postbaccalaureate Fellow (2021-2022)Pursuing M.D. at Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo

Akshaya Anand, Postbaccalaureate Fellow (2020-2021)

Julia Hartman, Postbaccalaureate Fellow (2019-2021)Pursuing M.D./Ph.D. at Virginia Commonwealth University School of Medicine

Chloe Borden, Postbaccalaureate Fellow (2019-2021)Pursuing M.D. at Cleveland Clinic Lerner College of Medicine, Case Western Reserve University

Janet Wang, Postbaccalaureate Fellow (2019-2020)Pursuing M.D. at University of Toledo College of Medicine and Life Sciences

Sarah Ayla Safran, Postbaccalaureate Fellow (2018-2019)Pursuing M.D. at Columbia University Vagelos College of Physicians and Surgeons

Theresa Alexander, Postbaccalaureate Fellow (2017-2018)Pursuing Ph.D. in Computational Biology at University of Maryland, College Park

## Image & Media Gallery

##### Latino patients with rheumatic disease and COVID-19

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Pie radar charts of clinical characteristics of rheumatic disease patients of Latino ethnicity. A, Presenting symptoms of COVID-19 positive rheumatic disease patients. B, Management of COVID-19 positive rheumatic disease patients. C, Baseline immunomodulatory treatment profile of COVID-19 positive rheumatic disease patients. D, Baseline immunomodulatory treatment profile of COVID-19 negative rheumatic disease patients.

##### Ayla's Farewell Party

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##### Ayla's Farewell Party

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##### NIAMS IRP Retreat 2019 Lab Picture

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##### NIAMS IRP Retreat 2019

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##### NIAMS IRP Retreat 2019-Ayla

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##### 3rd GRASP Workshop 2019

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##### LabTV Profile: Pravitt Gourh, M.D.

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LabTV Profile: Pravitt Gourh, M.D.

##### Associated amino acid positions in European American Scleroderma patients

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Ribbon model of the HLA-DR, HLA-DQ, HLA-DP proteins with independently associated amino acid residues in European Americans, based on Protein Data Bank entries 6atf, 1s9v, and 3lqz respectively.

Download High Res(2.93 MB)

##### Associated amino acid positions in African American Scleroderma patients

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Ribbon model of the HLA-DR, HLA-DQ, HLA-DP proteins with independently associated amino acid residues in African Americans, based on Protein Data Bank entries 6atf, 1s9v, and 3lqz respectively.

Download High Res(2.9 MB)

##### Three-dimensional principal components analysis plots

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(A) PCA plots of the 1000 Genomes populations (B) and the 1000 Genomes populations along with the scleroderma patients (red) and controls (blue). Each dot represents an individual subject and Americans of admixture (gold), African Americans (light blue), East Africans, East Asians (purple), Europeans (black), and West Africans (light green) are shown.

Download High Res(694.97 KB)

##### 2017 NHGRI Symposium and GREAT AWARD Ceremony

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##### 2nd GRASP Workshop 2018

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##### 1st GRASP Workshop 2017

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## Scientific Publications

## Selected Recent Publications

###             Risk Factors for COVID-19 and Rheumatic Disease Flare in a US Cohort of Latino Patients.        

73(7).

###             Use of Magnetic Resonance Imaging to Identify Immune Checkpoint Inhibitor-Induced Inflammatory Arthritis.        

3(2).

###             HLA and autoantibodies define scleroderma subtypes and risk in African and European Americans and suggest a role for molecular mimicry.        

117(1).

###             Brief Report: Whole-Exome Sequencing to Identify Rare Variants and Gene Networks That Increase Susceptibility to Scleroderma in African Americans.        

70(10).

###             Clinical and serological features of systemic sclerosis in a multicenter African American cohort: Analysis of the genome research in African American scleroderma patients clinical database.        

96(51).

###             Phenotypic and Genotypic Characterization and Treatment of a Cohort With Familial Tumoral Calcinosis/Hyperostosis-Hyperphosphatemia Syndrome.        

31(10).

###             Independent replication and meta analysis of association studies establish TNFSF4 as a susceptibility gene preferentially associated with the subset of anticentromere-positive patients with systemic sclerosis.        

39(5).

###             Novel identification of the IRF7 region as an anticentromere autoantibody propensity locus in systemic sclerosis.        

71(1).

###             Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy.        

7(7).

###             Association study of ITGAM, ITGAX, and CD58 autoimmune risk loci in systemic sclerosis: results from 2 large European Caucasian cohorts.        

38(6).

###             Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis.        

70(3).

###             Whole-blood gene expression profiling in ankylosing spondylitis shows upregulation of toll-like receptor 4 and 5.        

38(1).

###             Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus.        

42(5).

###             Systemic sclerosis and lupus: points in an interferon-mediated continuum.        

62(2).

###             The FAS -670A>G polymorphism influences susceptibility to systemic sclerosis phenotypes.        

60(12).

###             Polymorphisms in TBX21 and STAT4 increase the risk of systemic sclerosis: evidence of possible gene-gene interaction and alterations in Th1/Th2 cytokines.        

60(12).

###             Association of interleukin 23 receptor polymorphisms with anti-topoisomerase-I positivity and pulmonary hypertension in systemic sclerosis.        

36(12).

###             BANK1 functional variants are associated with susceptibility to diffuse systemic sclerosis in Caucasians.        

69(4).

###             Plasma cytokine profiles in systemic sclerosis: associations with autoantibody subsets and clinical manifestations.        

11(5).

###             Association of the C8orf13-BLK region with systemic sclerosis in North-American and European populations.        

34(2).

###             Clinical and genetic factors predictive of mortality in early systemic sclerosis.        

61(10).

###             Association of TNFSF4 (OX40L) polymorphisms with susceptibility to systemic sclerosis.        

69(3).

###             Primary biliary cirrhosis (PBC), PBC autoantibodies, and hepatic parameter abnormalities in a large population of systemic sclerosis patients.        

36(10).

###             Major histocompatibility complex (MHC) class II alleles, haplotypes and epitopes which confer susceptibility or protection in systemic sclerosis: analyses in 1300 Caucasian, African-American and Hispanic cases and 1000 controls.        

69(5).

###             CTGF polymorphism associated with systemic sclerosis.        

358(3).

###             Clinical, immunologic, and genetic features of familial systemic sclerosis.        

56(6).

###             An allograft inflammatory factor 1 (AIF1) single nucleotide polymorphism (SNP) is associated with anticentromere antibody positive systemic sclerosis.        

46(8).

###             Association of the PTPN22 R620W polymorphism with anti-topoisomerase I- and anticentromere antibody-positive systemic sclerosis.        

54(12).

###             Signatures of differentially regulated interferon gene expression and vasculotrophism in the peripheral blood cells of systemic sclerosis patients.        

45(6).

See all Publications on PubMed

## News & Highlights

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