Joshua B Wechsler, MD
Assistant Professor of Pediatrics (Gastroenterology, Hepatology, and Nutrition) and Medicine (Allergy and Immunology)
Focus of Work
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.[Shorten text]
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Education and Certification
- MD: Rush University (2006)
- Residency: Riley Hospital for Children, Pediatrics (2009)
- Fellowship: Northwestern University, McGaw Medical Center (Children’s Memorial Hospital), Pediatrics Gastroenterology (2012)
- Board Certification: Pediatric Gastroenterology, Pediatrics
Administrative office: 312-227-4200
Ann & Robert H. Lurie Children's Hospital of Chicago Box 65
225 E Chicago Avenue
Chicago IL 60611