Grants per year
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
2009 | Residency, Riley Hospital for Children |
2012 | Fellowship, Northwestern University, McGaw Medical Center (Children’s Memorial Hospital) |
Education/Academic qualification
MD, Medicine, Rush University
… → 2006
Research interests keywords
- 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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- 1 Similar Profiles
Collaborations and top research areas from the last five years
Grants
- 7 Finished
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Comparison of mast cells and IgE in adult EoE patients with FIRE symptoms
Wechsler, J. B. (PD/PI)
Northwestern Memorial Hospital, Digestive Health Foundation
6/1/20 → 6/30/22
Project: Research project
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TCR clonotype in adults with EoE undergoing food reintroduction
Wechsler, J. B. (PD/PI)
Northwestern Memorial Hospital, Digestive Health Foundation
6/1/20 → 6/30/22
Project: Research project
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Predictors of Treatment Response to Swallowed Steroids in Adults with EoE
Wechsler, J. B. (PD/PI) & Gonsalves, N. P. (Co-Investigator)
Northwestern Memorial Hospital
1/1/20 → 12/31/21
Project: Research project
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Investigating T-cell signature and clonality of food triggers in Eosinophilic Esophagitis
Wechsler, J. B. (PD/PI)
Northwestern Memorial Hospital, Digestive Health Foundation
7/1/18 → 6/30/19
Project: Research project
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Role of Mast Cell Activation in Eosinophilia Esophagitis
Wechsler, J. B. (PD/PI)
Consortium of Eosinophilic Gastrointestinal Disease Researchers
8/1/16 → 7/31/18
Project: Research project
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One-food versus 4-food elimination diet for pediatric eosinophilic esophagitis: A multisite randomized trial
Kliewer, K. L., Abonia, J. P., Aceves, S. S., Atkins, D., Bonis, P. A., Capocelli, K. E., Chehade, M., Collins, M. H., Dellon, E. S., Fei, L., Furuta, G. T., Gupta, S. K., Kagalwalla, A., Leung, J., Mir, S., Mukkada, V. A., Pesek, R., Rosenberg, C., Shoda, T. & Spergel, J. M. & 4 others, , Feb 2025, In: Journal of Allergy and Clinical Immunology. 155, 2, p. 520-532 13 p.Research output: Contribution to journal › Article › peer-review
3 Scopus citations -
The Minimally Invasive 1-Hour Esophageal String Test Monitors Therapeutic Changes in Mucosal Inflammation in Eosinophilic Esophagitis
Ackerman, S. J., Kagalwalla, A. F., Pan, Z., Wechsler, J., Keeley, K., Gonsalves, N., Hirano, I., Zalewski, A., Menard-Katcher, P., Menard-Katcher, C., Gupta, S. K., Chauhan, N., Grozdanovic, M., Atkins, D., Nguyen, N. & Furuta, G. T., Jan 1 2025, In: American Journal of Gastroenterology. 120, 1, p. 254-258 5 p.Research output: Contribution to journal › Article › peer-review
1 Scopus citations -
Advances and ongoing challenges in eosinophilic gastrointestinal disorders presented at the CEGIR/TIGERs Symposium at the 2024 American Academy of Allergy, Asthma & Immunology meeting
Wright, B. L., Abonia, J. P., Abud, E. M., Aceves, S. S., Ackerman, S. J., Braskett, M., Chang, J. W., Chehade, M., Constantine, G. M., Davis, C. M., Dellon, E. S., Doyle, A. D., Durban, R., Hill, D. A., Jensen, E. T., Kewalramani, A., Khoury, P., Klion, A. D., Kottyan, L. & Kuang, F. L. & 7 others, , Oct 2024, In: Journal of Allergy and Clinical Immunology. 154, 4, p. 882-892 11 p.Research output: Contribution to journal › Review article › peer-review
2 Scopus citations -
Ascending to New Heights for Novel Therapeutics for Eosinophilic Esophagitis
ASCENT WORKING GROUP, Jan 2024, In: Gastroenterology. 166, 1, p. 1-10 10 p.Research output: Contribution to journal › Article › peer-review
Open Access16 Scopus citations -
Clinical and molecular correlates of the Index of Severity for Eosinophilic Esophagitis
Sato, H., Dellon, E. S., Aceves, S. S., Arva, N. C., Chehade, M., Collins, M. H., Davis, C. M., Falk, G. W., Furuta, G. T., Gonsalves, N. P., Gupta, S. K., Hirano, I., Hiremath, G., Katzka, D. A., Khoury, P., Leung, J., Menard-Katcher, P., Pesek, R., Peterson, K. A. & Pletneva, M. A. & 5 others, , Aug 2024, In: Journal of Allergy and Clinical Immunology. 154, 2, p. 375-386.e4Research output: Contribution to journal › Article › peer-review
Datasets
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Mast cell activation in the systemic sclerosis esophagus
Tom, K. (Creator), Mehta, B. K. (Contributor), Hoffmann, A. (Creator), Aren, K. (Creator), Carns, M. (Creator), Lee, J. (Contributor), Martyanov, V. (Creator), Popovich, D. (Creator), Kosarek, N. (Creator), Wood, T. A. (Contributor), Brenner, D. (Creator), Carlson, D. A. (Creator), Ostilla, L. (Creator), Willcocks, E. (Creator), Bryce, P. (Creator), Wechsler, J. B. (Creator), Whitfield, M. L. (Creator) & Hinchcliff, M. (Creator), SAGE Journals, 2020
DOI: 10.25384/sage.c.5075239, https://sage.figshare.com/collections/Mast_cell_activation_in_the_systemic_sclerosis_esophagus/5075239
Dataset