UAB Center for Precision Animal Modeling (CPAM) - Disease Modeling Unit

ABSTRACT (DISEASE MODELING UNIT) The ability to sequence individual genomes and identify causative disease variants has progressed dramatically. The major bottlenecks now are evaluating if variants are causative, better understanding of why pathogenic variants cause the disease, and a means to preclinically evaluate therapeutics. The overall goal of the UAB Center for Precision Animal Modeling (CPAM) is to establish a pipeline for preclinical scientific discovery, disease modeling, and development of precision medicine-centered clinical interventions for community nominated ge- netic variants. The CPAM Disease Modeling Unit (DMU) supports the Center by creating and validating innova- tive animal models to recapitulate patient diseases at both molecular and phenotypic levels so that we can better understand disease pathogenesis and make highly relevant models ready for preclinical testing. A key compo- nent to establishing the biological relevance of any discovered genetic variation or anomaly is the assessment of that variation in an in vivo and/or human relevant in vitro model with the experimental power to validate the significance of the variation when compared to rigorous controls. The DMU has established the following aims to evaluate these patient variants: Aim 1 – High-Throughput Assessment of Variant Pathogenicity; Aim 2 - Ge- netic Engineering of Patient Variant Cell and Animal Models; and Aim 3 - Phenotypic Evaluation of Engineered Models. Ultimately, the DMU is an integral part of the CPAM pipeline and plays a crucial role in advancing our understanding of genetic variants and their clinical implications.