Biology subjects

Gordon, M. E.

Publications and source records attributed to Gordon, M. E..

3 recordsLinked to original sources

bioRxiv2025

Structure-Activity Relationship Studies Towards Analogues of Pleconaril as Novel Enterovirus-D68 Capsid-Targeting Antivirals

Non-polio enteroviruses (NPEV) such as enterovirus D68 (EV-D68) that are highly infectious and associated with polio-like neurological complications have caused out-breaks, globally, in recent years. While some clinical and preclinical compounds have shown efficacy against NPEV in-vitro, liabilities that caused historical compounds such as pleconaril to fall short of FDA approval still remain. We present herein SAR and SPR studies of analogues of clinical compounds such as pleconaril and vapendavir against EV-D68 as a representative NPEV. Numerous structurally differentiated analogues with EV-D68 antiviral activity and useful ADME properties were discovered, which could serve as starting points for future EV drug discovery campaigns. Screening against a panel of enteroviruses revealed moderately broad-spectrum anti-EV activity of compound 26.

pharmacology and toxicology↗

bioRxiv2023

Sequential Switching Through IgG1 is Redundant for Allergic Reactivity and Memory to Allergens

Allergic reactions to foods are driven by allergen-binding immunoglobulin (Ig)E antibodies. IgE- expressing cells can be generated through a sequential class switching pathway where activated B cells first switch to an intermediary isotype, most frequently IgG1, and then to IgE. It has been proposed that sequential class switch recombination is important in generating high affinity IgE, augmenting anaphylactic reactions, and in holding the memory of IgE responses. Here, we observed surprising redundancy of sequential switching through IgG1 for the functional affinity of the IgE repertoire against multiple food allergens as well as for the ability of IgE to elicit anaphylaxis. We further found that sequential switching via IgG1 was irrelevant for allergic memory. These results indicate that allergen-specific IgG1 B cells are redundant in sensitization, anaphylaxis, and food allergy persistence, thereby implicating other switching pathways as important considerations in the development of therapeutics for allergic diseases.

immunology↗

bioRxiv2019

Microbial regulation of enteric eosinophils and its impact on tissue remodeling and Th2 immunity

Eosinophils have emerged as multifaceted cells that contribute to tissue homeostasis. However, the factors that control their frequency and function at mucosal sites remain unclear. Here, we investigated the role of the microbiota in regulating enteric eosinophils. We found that small intestinal (SI) eosinophilia was significantly greater in germ-free (GF) mice compared to specific pathogen free (SPF) controls. This phenomenon was associated with enteric overexpression of signals that mediate attraction, retention and survival of eosinophils, and was reversed by colonization. Additionally, we generated a novel strain of eosinophil-deficient GF mice. These mice displayed intestinal fibrosis and were less prone to allergic sensitization as compared to GF controls. Overall, our study demonstrates that commensal microbes regulate intestinal eosinophil frequency and function, which impacts tissue repair and allergic sensitization to food antigens. These data support a critical interplay between the commensal microbiota and intestinal eosinophils in shaping homeostatic, innate and adaptive immune processes in health and disease.

immunology↗