Research Objectives
The Rothenberg laboratory has several broad objectives that encompass the specific research hypotheses currently being investigated in the laboratory.
- Elucidating the cellular and molecular processes involved in allergic responses in the gastrointestinal tract and lung using approaches that include novel models of allergic responses in vivo and in vitro.
- Testing the importance of key molecules including chemokines and cytokines in vivo using transgenic and gene-targeted mice.
- Biochemically characterizing the transcriptional programs, regulating molecules and signal transduction mechanisms responsible for eosinophil development and activation.
- Testing the importance and blockade of these pathways in patients with inflammatory diseases such as eosinophilic esophagitis (EE or EoE) and hypereosinophilic syndromes (HES).
- Identifying genes and key check points that predispose to eosinophilic and other allergic disorders.
Ongoing Research Projects
Below are many of the main areas of present interest that are currently being investigated in the laboratory.
Role of Eotaxins and CCR3 in IL-13-induced Asthma
The major goal of this project is to define the individual and combined roles of eotaxin-1, eotaxin-2, IL-5, and CCR3 in IL-13-elicited lung responses.
Mechanistic Analysis of Eosinophilic Esophagitis
The major goal of this project is to understand the development of experimental eosinophilic esophagitis in mice by exploring the mechanism of antigen sensitization and dendritic cell involvement.
Epithelial-derived Eotaxin-3 and Eosinophilic Esophagitis
The major goal of this project is to understand the role of eotaxin-3 in human eosinophilic esophagitis. Studies involve cellular distribution of eotaxin-3 and its receptor, the role and mechanisms of an eotaxin-3 single-nucleotide polymorphism in disease pathogenesis and the effect of glucocorticoid therapy on eotaxin-3 expression and esophageal transcript profiles.
IL-13 and Eosinophilic Esophagitis
The major goal of this project is to identify the expression and role of IL-13 in eliciting human eosinophilic esophagitis and in experimental eosinophilic esophagitis in mice.
IL-13-Associated Eosinophil Lung Responses
The major goal of this project is to broaden our understanding of asthma-associated lung pathology by aiming to clarify the unique and comparative effects of interrupting IL-4, IL-13 and/or their receptors in asthma.
Regulation of Gastrointestinal Eosinophils
The major goals of this project are to analyze gastrointestinal eosinophils at baseline and during Th2-associated allergic responses in the gastrointestinal tract.
Candidate Gene Approach and Genome-wide Association Analysis for Eosinophilic Esophagitis
The major goal is to take a candidate gene approach to identify genetic risk factors for EE and to gain molecular insight into disease pathogenesis.
The Role of CREB-Binding Protein (CBP) in Eosinophilic Esophagitis
The major goal of this project is to analyze the role of CREB-binding protein (CBP) in the pathogenesis of eosinophilic esophagitis.
The Mechanism of Steroid Action and Resistance in Allergic Disease
The major goal of this project is to optimize the efficacy of steroids for allergic disease. Model systems in vitro and in vivo are employed.
Epigenetic Regulation of Allergic Disease
The major goal of this project is to elucidat gene-environment interactions in allergic disease, to define the epigenetic mechanism that accounts for these interactions and their clinical and therapeutic significance.
