PROJECT SUMMARY
Experimentally induced animal models of disease play a critical role in the development, evaluation and
optimization of therapeutics for human disease. With the advent of genetic engineering, such model systems
have substantially improved; however, translational failure rates remain high for most disease entities. One
promising approach involves using pet dogs with spontaneous disease to evaluate treatment strategies for
diseases such as cancer, heart failure and neurodegeneration prior to human trials, with the goal of improving
clinical outcomes. Beyond their inherent biological relevance, translational advantages of this model include
longitudinal assessment of individual patients using diagnostics and interventions that parallel human processes,
compressed disease timelines that permit rapid evaluation of therapeutic impact, and the freedom to study
unique treatment combinations in lieu of standards of care. As human medicine progressively adopts strategies
designed to prevent disease progression through early detection and intervention, studies in pet dogs have the
potential to contribute valuable preclinical information. Several resources now support such work including the
NCI Integrated Canine Data Commons, SMART IACUC for multi-site studies, the CTSA One Health Alliance and
a markedly improved canine reference genome (CanFam4) and associated key omics tools. Despite these
advances, effective alignment and integration of data generated from pet dogs with human health systems
remains a substantial challenge. To begin addressing this gap, we developed a veterinary data model that is
harmonized with the Observational Medical Outcomes Partnership Common Data Model (OMOPv5+ CDM) and
generated tools for core research infrastructure including, TRANSLATOR (TRanslational ANimal Shared
ColLAboraTive Observational Research). In the current application, we will build upon our prior work and
use pet dogs to develop, validate, and optimize tools for early disease detection, and in parallel, resource
these studies to iteratively advance methodologies for improving connectivity and application of such
data sets to human health processes. To accomplish this, we will 1) credential a liquid biopsy assay for early
detection of cancer relapse in pet dogs and rapidly test innovative strategies to prevent progression; 2) validate
an integrated ultrasound/exosome diagnostic for early detection of cardiac cachexia in pet dogs and assess
novel approaches to halt wasting; and 3) further enhance the utility of our OMOPv5+ CDM and related informatics
tools to realize the translational potential of pet dog trials. An outstanding team blending human and veterinary
medicine, comparative genomics, biomedical engineering, research informatics infrastructure and preclinical
translational modeling, supported by an advisory panel of human health experts, will facilitate successful
completion of stated milestones. Importantly, the proposed work integrates with and is supported by the parent
UM1, ensuring that scientific advancements for early disease detection and intervention co-evolve with
methodologies that improve fundamental processes necessary for interpretation and future utility of the science.
