@article{cortes_brodsky_chen_pridgen_odle_snider_cruse_putikova_masuda_doyle_et al._2022, title={Immunologic and pathologic characterization of a novel swine biomedical research model for eosinophilic esophagitis}, volume={3}, ISSN={["2673-6101"]}, DOI={10.3389/falgy.2022.1029184}, abstractNote={Eosinophilic esophagitis (EoE) is a chronic allergy-mediated condition with an increasing incidence in both children and adults. Despite EoE's strong impact on human health and welfare, there is a large unmet need for treatments with only one recently FDA-approved medication for EoE. The goal of this study was to establish swine as a relevant large animal model for translational biomedical research in EoE with the potential to facilitate development of therapeutics. We recently showed that after intraperitoneal sensitization and oral challenge with the food allergen hen egg white protein (HEWP), swine develop esophageal eosinophilia—a hallmark of human EoE. Herein, we used a similar sensitization and challenge treatment and evaluated immunological and pathological markers associated with human EoE. Our data demonstrate that the incorporated sensitization and challenge treatment induces (i) a systemic T-helper 2 and IgE response, (ii) a local expression of eotaxin-1 and other allergy-related immune markers, (iii) esophageal eosinophilia (>15 eosinophils/0.24 mm2), and (iv) esophageal endoscopic findings including linear furrows and white exudates. Thereby, we demonstrate that our sensitization and oral challenge protocol not only induces the underlying immune markers but also the micro- and macro-pathological hallmarks of human EoE. This swine model for EoE represents a novel relevant large animal model that can drive translational biomedical research to develop urgently needed treatment strategies for EoE.}, journal={FRONTIERS IN ALLERGY}, author={Cortes, Lizette M. and Brodsky, David and Chen, Celine and Pridgen, Tiffany and Odle, Jack and Snider, Douglas B. and Cruse, Glenn and Putikova, Arina and Masuda, Mia Y. and Doyle, Alfred D. and et al.}, year={2022}, month={Nov} }
 @article{snider_arthur_falduto_olivera_ehrhardt-humbert_smith_smith_metcalfe_cruse_2022, title={Targeting KIT by frameshifting mRNA transcripts as a therapeutic strategy for aggressive mast cell neoplasms}, volume={30}, ISSN={["1525-0024"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85114708401&partnerID=MN8TOARS}, DOI={10.1016/j.ymthe.2021.08.009}, abstractNote={Activating mutations in c-KIT are associated with the mast cell (MC) clonal disorders cutaneous mastocytosis and systemic mastocytosis and its variants, including aggressive systemic mastocytosis, MC leukemia, and MC sarcoma. Currently, therapies inhibiting KIT signaling are a leading strategy to treat MC proliferative disorders. However, these approaches may have off-target effects, and in some patients, complete remission or improved survival time cannot be achieved. These limitations led us to develop an approach using chemically stable exon skipping oligonucleotides (ESOs) that induce exon skipping of precursor (pre-)mRNA to alter gene splicing and introduce a frameshift into mature KIT mRNA transcripts. The result of this alternate approach results in marked downregulation of KIT expression, diminished KIT signaling, inhibition of MC proliferation, and rapid induction of apoptosis in neoplastic HMC-1.2 MCs. We demonstrate that in vivo administration of KIT targeting ESOs significantly inhibits tumor growth and systemic organ infiltration using both an allograft mastocytosis model and a humanized xenograft MC tumor model. We propose that our innovative approach, which employs well-tolerated, chemically stable oligonucleotides to target KIT expression through unconventional pathways, has potential as a KIT-targeted therapeutic alone, or in combination with agents that target KIT signaling, in the treatment of KIT-associated malignancies.}, number={1}, journal={MOLECULAR THERAPY}, author={Snider, Douglas B. and Arthur, Greer K. and Falduto, Guido H. and Olivera, Ana and Ehrhardt-Humbert, Lauren C. and Smith, Emmaline and Smith, Cierra and Metcalfe, Dean D. and Cruse, Glenn}, year={2022}, month={Jan}, pages={295–310} }