Brandon Tepper
Pronouns: he/him
Research Mentor(s): Fatima Fattahi
Research Mentor School/College/Department: Department of Internal Medicine, Division of Pulmonary & Critical Care Medicine / Medicine
Program:
Authors: Brandon Tepper, Laura Vallance, Julia Holden, Moamen Shukeir, Kareem Hussein, Fatemeh Fattahi, Ulus Atasoy
Session: Session 2: 10:00 am – 10:50 am
Poster: 62
Abstract
Background: Chronic allergic asthma presents a significant challenge in treatment development due to its complex interplay of lung inflammation and airway remodeling. Upon prolonged exposure to allergens, lung mesenchymal cells (MCs) are stimulated by cytokines IL-13 and IL-4, leading to collagen accumulation, fibrosis, and airway remodeling. Our studies incorporate both in vivo and in vitro approaches to model chronic allergic asthma. Methods: In our in vivo studies, we utilize mouse models of chronic allergic asthma, inducing the condition via intranasal administration of House Dust Mite (HDM) over 6 weeks (5 days a week). Simultaneously, our in vitro experiments aim to elucidate the effects of IL-13 and IL-4 on lung MCs, investigating their protein expression and immune cell recruitment. We hypothesize the involvement of the MNK/eIF4E pathway in this process, which we validate using the eFT-508 inhibitor to decrease MC activation and mitigate airway remodeling. During the final two weeks of the experimental period, a group of mice challenged with HDM are treated with the eFT-508 inhibitor through oral gavage. At the end of the experimental period, the lungs are harvested to examine the inflammatory responses specifically in lung MCs. Additionally, in our in vitro studies, lung MCs are isolated from mice using collagenase, followed by treatment with IL-13 and IL-4 (20 ng/ml each) with or without eFT-508 inhibitor. Western blot technique is then used to investigate the protein expression of fibrogenous proteins, such as collagen. Results: We expect our results to reveal the effectiveness of the eFT-508 inhibitor in decreasing airway inflammation in mice challenged with HDM and in vitro treated with cytokines (IL-13 and IL-4). Consequently, untreated mice with eFT-508 inhibitor are expected to exhibit increased inflammatory protein expression, as well as significant collagen accumulation and fibrosis. The natural response mechanism of MCs can lead to severe airway remodeling, potentially causing obstruction and reduced airflow/oxygenation, which is reduced by the eFT-508 inhibitor. Conclusions: The eFT-508 inhibitor sheds light on new therapeutic approaches for treating chronic allergic asthma. By blocking the MNK/eIF4E signaling pathway, the activation of MCs by cytokines such as IL-13 is inhibited, thus reducing inflammation and mitigating airway remodeling.
