Joshua Brian Wechsler

  • 1103 Citations
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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

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

Fingerprint Dive into the research topics where Joshua Brian Wechsler is active. These topic labels come from the works of this person. Together they form a unique fingerprint.

  • 11 Similar Profiles
Eosinophilic Esophagitis Medicine & Life Sciences
Mast Cells Medicine & Life Sciences
Gastrointestinal Diseases Medicine & Life Sciences
Histamine Medicine & Life Sciences
Eosinophils Medicine & Life Sciences
Histamine Receptors Medicine & Life Sciences
Immunoglobulin E Medicine & Life Sciences
Leukemia, Megakaryoblastic, Acute Medicine & Life Sciences

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Grants 2015 2020

Research Output 2002 2020

  • 1103 Citations
  • 26 Article
  • 4 Review article
  • 2 Letter

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

Patient Advocacy
Gastrointestinal Diseases
National Institutes of Health (U.S.)
Patient Care
Research Personnel

Mast Cell Infiltration Is Associated With Persistent Symptoms and Endoscopic Abnormalities Despite Resolution of Eosinophilia in Pediatric Eosinophilic Esophagitis

Bolton, S. M., Kagalwalla, A. F., Arva, N. C., Wang, M. Y., Amsden, K., Melin-Aldana, H., Dellon, E. S., Bryce, P. J., Wershil, B. K. & Wechsler, J. B., Feb 1 2020, In : The American journal of gastroenterology. 115, 2, p. 224-233 10 p.

Research output: Contribution to journalArticle

Eosinophilic Esophagitis
Mast Cells
2 Citations (Scopus)

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

Eosinophilic enteropathy
Area Under Curve
2 Citations (Scopus)

Cellular Defects in CVID Patients with Chronic Lung Disease in the USIDNET Registry

The USIDNET Consortium, Aug 15 2019, In : Journal of Clinical Immunology. 39, 6, p. 569-576 8 p.

Research output: Contribution to journalArticle

Common Variable Immunodeficiency
Lung Diseases
Chronic Disease
Interstitial Lung Diseases

Histamine-driven responses are sustained via a bioactive metabolite

Velez, T. E., Byrne, A. J., Wechsler, J. B., Krier-Burris, R. A., Hulse, K. E. & Bryce, P. J., Jun 2019, In : Journal of Allergy and Clinical Immunology. 143, 6, p. 2287-2290.e1

Research output: Contribution to journalArticle