Wake Forest University Vesicant Exposure Resource and Coordination Core

Project Summary/Abstract Early-stage development of medical countermeasures (MCMs) for hazardous chemicals can be complicated by several factors, including limited expertise in working with highly toxic and restricted chemicals and a diverse array of experimental models of varying relevance. We propose to establish the Wake Forest University Vesicant

Exposure Resource and Coordination Core (Vesicant ExRC) to provide a comprehensive suite of experimental models, innovative analytical methods and interactive study design protocols to support CCRP investigators. Dr. McNutt will serve as the overall Director of the Vesicant ExRC. He will be joined by a multidisciplinary scientific

team with extensive expertise in vesicant studies and an administrative team with proven experience in managing large, multi-institutional programs under BARDA, NIH and DoD funding. The overall goal of the Vesicant ExRC is to take advantage of our established expertise studying vesicant injury in vivo and in vitro to

develop a state-of-the-art facility that accelerates and enhances fundamental and translational studies. Our approach is enabled by the established repertoire of well-characterized experimental models used at Wake Forest to study fundamental effects of vesicants on ocular, dermal and pulmonary tissues. The experimental

methods will focus on three primary models; in vivo studies using mouse and rabbit preclinical models of corneal injury; ex vivo exposures using commercially procured eyes for acute and mechanistic studies; and in vitro studies using phenotypically mature, full-thickness upper airway and skin microphysiological models. The

Vesicant ExRC will be organized and executed through five specific aims: (1) Establish the Vesicant ExRC as a collaborative vesicant research resource; (2) Enhance collaborative studies through advanced analytical methods; (3) Ensure effective communication and coordination between Vesicant ExRC and stakeholders; (4)

Develop resources to education stakeholders and disseminate standardized methods and findings; and (5) transition the Vesicant ExRC to become a sustainable resource. These aims will be achieved through the development and coordination of an Administrative Core, Coordination Core and Research Support Core to

manage ExRC operations; establishment of a Steering Committee and External Advisory Committee to provide strategic guidance; implementation of facility website for scheduling, marketing and communications; and education of stakeholders and the broader CCRP Network in experimental approaches. The ability of the

Vesicant ExRC to rapidly develop, standardize and disseminate proven methods for the study of highly toxic vesicants is anticipated to directly enhance the CCRP mission by accelerating fundamental studies into toxic mechanisms and improving early-stage MCM development.