Joshua Brian Wechsler

  • 1021 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

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

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Grants 2015 2020

Research Output 2002 2019

  • 1021 Citations
  • 23 Article
  • 3 Review article
  • 2 Letter
1 Citation (Scopus)

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

The USIDNET Consortium, Jan 1 2019, In : Journal of Clinical Immunology.

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 1 2019, In : Journal of Allergy and Clinical Immunology. 143, 6, p. 2287-2290.e1

Research output: Contribution to journalArticle


Oligoclonal immunoglobulin repertoire in biliary remnants of biliary atresia

Taylor, S. A., Malladi, P., Pan, X., Wechsler, J. B., Hulse, K. E., Perlman, H. R. & Whitington, P. F., Dec 1 2019, In : Scientific reports. 9, 1, 4508.

Research output: Contribution to journalArticle

Open Access
Oligoclonal Bands
Biliary Atresia
Liver Diseases

One-Hour Esophageal String Test: A Nonendoscopic Minimally Invasive Test That Accurately Detects Disease Activity in Eosinophilic Esophagitis

Ackerman, S. J., Kagalwalla, A. F., Hirano, I., Gonsalves, N., Katcher, P. M., Gupta, S., Wechsler, J. B., Grozdanovic, M., Pan, Z., Masterson, J. C., Du, J., Fantus, R. J., Alumkal, P., Lee, J. J., Ochkur, S., Ahmed, F., Capocelli, K., Melin-Aldana, H., Biette, K., Dubner, A. & 6 others, Amsden, K., Keeley, K., Sulkowski, M., Zalewski, A., Atkins, D. & Furuta, G. T., Oct 1 2019, In : The American journal of gastroenterology. 114, 10, p. 1614-1625 12 p.

Research output: Contribution to journalArticle

Eosinophilic Esophagitis
Digestive System Endoscopy

Overestimation of the diagnosis of eosinophilic colitis with reliance on billing codes

Muir, A. B., Jensen, E. T., Wechsler, J. B., Menard-Katcher, P., Falk, G. W., Aceves, S. S., Furuta, G. T., Dellon, E. S., Rothenberg, M. E. & Spergel, J. M., Sep 1 2019, In : Journal of Allergy and Clinical Immunology: In Practice. 7, 7, p. 2434-2436 3 p.

Research output: Contribution to journalArticle