Shehzad Sheikh

About

Shehzad Z. Sheikh, MD, PhD, is a Full Professor with Tenure in Medicine and Genetics at the University of North Carolina School of Medicine, specializing in the Division of Gastroenterology and Hepatology within the Center of Gastrointestinal Biology and Disease. His research focuses on deciphering the chromatin code in Inflammatory Bowel Diseases (IBD), aiming to understand the molecular and genetic mechanisms underlying these complex conditions. Dr. Sheikh leads a multidisciplinary lab that integrates genomic, transcriptomic, and epigenomic approaches to investigate the pathophysiology of IBD and related gastrointestinal disorders. His work involves the use of advanced techniques such as ATAC-seq, CUT&RUN, and RNA-seq to study chromatin structure and gene regulation in both human and mouse models. Through this research, Dr. Sheikh contributes to identifying key drivers of gut inflammation and disease heterogeneity, which may inform the development of targeted therapies for IBD patients.

Research topics

• Biology
• Medicine
• Pathology
• Internal medicine
• Genetics
• Cell biology
• Computational biology
• Immunology
• Molecular biology
• Endocrinology

Selected publications

• Large-scale sequencing identifies multiple genes and rare variants associated with Crohn’s disease susceptibility

  Nature Genetics · 2022 · 180 citations

  DOI

• Single-Cell Analysis Reveals Unexpected Cellular Changes and Transposon Expression Signatures in the Colonic Epithelium of Treatment-Naïve Adult Crohn’s Disease Patients

  Cellular and Molecular Gastroenterology and Hepatology · 2022 · 56 citations

  BACKGROUND & AIMS: The intestinal barrier comprises a monolayer of specialized intestinal epithelial cells (IECs) that are critical in maintaining mucosal homeostasis. Dysfunction within various IEC fractions can alter intestinal permeability in a genetically susceptible host, resulting in a chronic and debilitating condition known as Crohn's disease (CD). Defining the molecular changes in each IEC type in CD will contribute to an improved understanding of the pathogenic processes and the identi…

  DOI

• Increased colonic expression of ACE2 associates with poor prognosis in Crohn’s disease

  Scientific Reports · 2021 · 24 citations

  Senior authorCorresponding

  The host receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small intestine. Our aim was to study colonic ACE2 expression in Crohn's disease (CD) and non-inflammatory bowel disease (non-IBD) controls. We hypothesized that the colonic expression levels of ACE2 impacts CD course. We examined the expression of colonic ACE2 in 67 adult CD and 14 NIBD control patients using RNA-seq and quantitative (q) RT-PCR. We validated ACE2 protein expression and localization…

  PublisherOA PDFDOI

• Biochemical and rheological analysis of human colonic culture mucus reveals similarity to gut mucus

  Biophysical Journal · 2021 · 23 citations

  DOI

• Decreased Colonic Activin Receptor-Like Kinase 1 Disrupts Epithelial Barrier Integrity in Patients With Crohn’s Disease

  Cellular and Molecular Gastroenterology and Hepatology · 2020 · 22 citations

  Senior authorCorresponding

  BACKGROUND & AIMS: Intestinal epithelial cell (IEC) barrier dysfunction is critical to the development of Crohn's disease (CD). However, the mechanism is understudied. We recently reported increased microRNA-31-5p (miR-31-5p) expression in colonic IECs of CD patients, but downstream targets and functional consequences are unknown. METHODS: microRNA-31-5p target genes were identified by integrative analysis of RNA- and small RNA-sequencing data from colonic mucosa and confirmed by quantitative po…

  DOI

Recent grants

• Interpreting molecular role of DNA variants associated with Crohn's Disease through integrative analysis of open chromatin, epigenome and transcriptome data in diverse and relevant tissues and cells

  NIH · $588k · 2014–2017

• Integrative Genetic and Genomic Analyses in the Inflammatory Bowel Disease

  NIH · $901k · 2016–2020

• Microbial and inflammatory regulation of intestinal epithelial gene transcription

  NIH · $35.6M · 2013–2025

Frequent coauthors

• Terrence S. Furey

  University of North Carolina at Chapel Hill

  57 shared

• Scott E. Plevy

  Protagonist Therapeutics (United States)

  37 shared

• Matthew R. Schaner

  University of North Carolina at Chapel Hill

  27 shared

• Caroline Beasley

  University of North Carolina at Chapel Hill

  26 shared

• Hans Herfarth

  University of North Carolina at Chapel Hill

  22 shared

• Erin C. Steinbach

  Sorbonne Université

  21 shared

• Katsuyoshi Matsuoka

  Toho University

  21 shared

• Praveen Sethupathy

  Cornell University

  19 shared

Labs

• Sheikh LabPI

Education

• Ph.D., Toxicology

  University of North Carolina at Chapel Hill

  2000

• M.D., Medicine

  University of North Carolina at Chapel Hill

  1995

• B.S., Biology

  University of North Carolina at Chapel Hill

  1991

Similar researchers at University of North Carolina at Chapel Hill

• Paul Watkinsh-107
• Scott Randellh-100
• Alexander Tropshah-93