Joshua Brian Wechsler

  • 1229 Citations
20022020

Research output per year

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Personal profile

Research Interests

Eosinophilic Gastrointestinal Diseases

As a physician-scientist, my long-term objective is to define immunologic mechanisms of gastrointestinal inflammation that drive clinical phenotype/outcome. This is key to identifying novel therapeutic targets, improving outcomes, reducing morbidity and personalizing care. My focus is on Eosinophilic Gastrointestinal Diseases (EGID), in particular Eosinophilic Esophagitis (EoE), Eosinophilic Gastritis (EG), and Eosinophilic Gastroenteritis (EGE). EoE, in particular, involves symptoms of esophageal dysfunction and eosinophil-predominant inflammation isolated to the esophagus secondary to chronic exposure to one or more dietary antigens. Left untreated, the long-term complication of the diseases is due to fibrostenosis. In addition to eosinophilia, most patients have mucosal mastocytosis. Mast cells are tissue resident immune cells, well-described as a component of the chronic inflammation seen in both disease. Packed with histamine granules, mast cells can be triggered by luminal contents to release histamine through degranulation. Histamine, a pro-inflammatory small molecule derived from histidine, acts through 4 receptors (H1R-H4R), of which the gut expresses all but H3R. Notably, H4R expression is restricted to the immune system. In addition, mast cells release several proteases, which are also stored in granules, along with de novo synthesized leukotrienes, cytokines, and chemokines. My laboratory studies the role of mast cell activation, histamine and its receptors, and the granule-associated proteases in driving clinical, endoscopic and histologic changes in EGIDs. In addition, my laboratory studies the role of mast cells activation in Ulcerative Colitis (UC), a subtype of inflammatory bowel disease (IBD) characterized by blood diarrhea, and T-helper lymphocyte type 2 inflammation restricted to the colonic mucosa. Recently, we identified a role for mucosal mast cell derived histamine and the histamine 4-receptor (H4R) in recruiting neutrophils to the colon. We are actively working to identify the cellular target expressing H4R and its role. In the laboratory, animal models of these diseases are utilized to characterize the requirements and consequences of mast cells and their mediators to define mechanism. We are actively studying the interaction between mast cells and the epithelium and build 3-D Air liquid interface models of the esophagus to better define this. With the knowledge gained from these models, patient biopsies are interrogated by RNA (single cell and bulk) and protein analysis to corroborate the findings, further an understanding of the disease process, and support the need for new therapeutic options.

Certifications and Licenses

Pediatric Gastroenterology
Pediatrics

Training Experience

2009Residency, Riley Hospital for Children
2012Fellowship, Northwestern University, McGaw Medical Center (Children’s Memorial Hospital)

Education/Academic qualification

MD, Rush University

… → 2006

Research interests

  • Digestive System (including gallbladder and liver)
  • Eosinophilic Esophagitis
  • Eosinophilic Gastrointestinal Disease
  • Food Allergy and Gastrointestinal Disease
  • Gut Immunology
  • Immunology
  • Inflammation
  • Inflammatory Bowel Disease
  • Molecular Biology
  • Outcome Measures
  • Pediatric Gastroenterology
  • Translational Research

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Grants

  • Research Output

    • 1229 Citations
    • 27 Article
    • 4 Review article
    • 2 Letter
    • 1 Comment/debate

    Advancing patient care through the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR)

    Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR), Jan 2020, In : Journal of Allergy and Clinical Immunology. 145, 1, p. 28-37 10 p.

    Research output: Contribution to journalArticle

  • Esophageal type 2 cytokine expression heterogeneity in eosinophilic esophagitis in a multisite cohort

    Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR), Jun 2020, In : Journal of Allergy and Clinical Immunology. 145, 6, p. 1629-1640.e4

    Research output: Contribution to journalArticle

    Open Access
  • 1 Scopus citations
  • 2 Scopus citations

    Molecular, endoscopic, histologic, and circulating biomarker-based diagnosis of eosinophilic gastritis: Multi-site study

    Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR), Jan 2020, In : Journal of Allergy and Clinical Immunology. 145, 1, p. 255-269 15 p.

    Research output: Contribution to journalArticle

  • 3 Scopus citations