Animal Model Core

SUMMARY Evaluating the efficacy of candidate compounds against drug resistant fungal pathogens in robust and reproducible animal models of infection is critical to advancing these compounds towards preclinical candidacy. To contribute to the rapid development of such medical countermeasures, the Animal Model Core will provide clinically relevant systemic, pulmonary, and urinary tract fungal infection models. Specifically, the Aims of the core are to 1) assess lead compounds against high threat fungal pathogens including Candida spp. and A. fumigatus in small animal infection models and 2) provide state of the art analytical services on host response and fungal bio-burden distribution to assess and quantify lead compound treatment efficacy. The Core leverages the AAALAC accredited, 40,000 sq ft Center for Discovery and Innovation Research Animal Facility (CDI RAF), which has dedicated space for the study of BSL2 pathogens. Under the direction of Dr. Andrew Nelson, the CDI Research Animal Specialist Team (the Core) currently conducts model studies of mice, rats, hamsters, guinea pigs, and rabbits to support the drug development efforts of pharmaceutical and academic partners. This includes supporting an NIH supported Antiviral Drug Discovery (AViDD) Center for Pathogens of Pandemic Concern and a second NIH Center of Excellence in Translational Research targeted at developing novel lead compounds against drug resistant bacterial infections. The experienced and dedicated animal model team routinely performs a wide range of infection models achieved through multiple routes of infection (IV, IP, aerosol, intranasal, intratracheal, intramuscular, cutaneous) and assesses these models with an array of markers for disease (microbial burden, host immune response assays, in vivo pulmonary function testing, clinical pathology, histopathology, advanced preclinical imaging modalities). The Core operations are governed by a well-developed quality control, management, and communication plan. The Core will ensure that all optimized lead compounds are rapidly advanced through the pipeline. The Core maintains close and constant lines of communication with the Projects and other Cores to guarantee that adjustments in experimental design and throughput are executed as appropriate. Further, the Core adheres to all regulatory and institutional requirements for animal use and biosafety. Thus, the Animal Model Core is well positioned to serve the in vivo preclinical needs of the Projects of this CETR.