Rothenberg CURED Research Lab
Comprehensive Research on Mechanisms of Allergic Response
The Rothenberg CURED Research Laboratory, supported by the Campaign Urging Research for Eosinophilic Diseases (CURED), is focused on elucidating the mechanisms of allergic responses, especially in mucosal tissues such as the gastrointestinal tract and lung. The goal of our research is to identify mechanisms of allergic inflammation with the aim of developing and testing novel diagnostics and pharmaceutical targets for the treatment and cure of patients with a variety of allergic diseases, especially eosinophilic gastrointestinal disorders (EGID) [e.g. eosinophilic esophagitis (EoE)], hypereosinophilic syndrome (HES), asthma and food allergies.
Bench to Bedside and Back
We have identified and biologically characterized several critical pathways that regulate allergic responses. Our research integrates multidisciplinary basic studies, with particular emphasis on modern genetic approaches, stem cell research, biochemistry, cell biology, informatics, translational research employing novel in vivo and ex vivo systems developed by our laboratory (to access datasets, visit EGIDExpress Data Sharing in Current Projects), and clinical studies designed to test proof-of-concept theories and novel therapeutics directly in humans.
Focus on Eosinophils: Homeostasis and Disease
Eosinophils have been considered end-stage cells involved in host protection against parasites. However, numerous lines of evidence have now changed this perspective by showing that eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of diverse inflammatory responses, as well as modulators of innate and adaptive immunity. For example, the Rothenberg laboratory has found that intestinal eosinophils regulate the production of secretory immunoglobulin A (IgA) and regulate intestinal commensal flora.
We are examining new views on the role of eosinophils in homeostatic function, including developmental biology and innate and adaptive immunity (as well as interaction with mast cells, B cells and T cells). We are studying the molecular steps involved in eosinophil development and trafficking, with special attention to the important role of eosinophil-selective cytokines such as interleukin 5 (IL-5), the eotaxin subfamily of chemokines, IL-13 and epithelial gene products.
We are investigating the role of eosinophils in disease processes including infections, asthma and gastrointestinal disorders. We are studying the consequences of genetically engineered eosinophil-deficient mice and eosinophil depletion in humans ("human eosinophil knockouts"). Genetic approaches to understanding eosinophil-associated human diseases are a focus area. Why patients develop allergic disorders, focused on genetic and environmental factors and their interactions, are priority research topics. Finally, we are pursuing strategies for diagnostics and patient-reported outcomes and targeted therapeutic intervention in allergic diseases with a focus on eosinophil-mediated diseases.