UAB Center for Precision Animal Modeling (CPAM) - Resource and Service Section

University Of Alabama At Birmingham, Birmingham AL

Investigators

Linked publications, trials & patents

Abstract

ABSTRACT (RESOURCE AND SERVICE SECTION, RSS) The Resource and Service Section (RSS) supports CPAM and the disease research community by accelerating the genetic, biochemical, and cellular analyses of pathogenic mechanisms of disease. The RSS accomplishes this by providing access to rigorously controlled in vivo/in vitro models for the assessment of human disease variants and testing of therapeutic strategies. The RSS contributes to key areas of the CPAM’s pipeline to support the Center’s mission including Cell Line RNA Profiling, Variant Specific Assay Development; Quality Control, Special Phenotyping, Cryopreservation, and Distribution; and Drug Toxicology and Therapeutic Screening. One of CPAM’s strengths is the diversity of animal and cell systems that we utilize to generate models allowing comparative analyses. The RSS will archive and distribute models created by CPAM’s Disease Modeling Unit to outside investigators and/or NIH-sponsored national repositories. We are also a checkpoint that helps ensure quality control, data management, data distribution, and data input for bioinformatic analyses performed by the Bioinformatics Section and for entry into the CPAM data curation portal called Rosalution. In our pilot phase (CPAM1.0) our emphasis was on model generation. With the renewal (CPAM2.0), we have more emphasis on disease relevant phenotyping and therapeutics testing. Indeed, for select cases the DMU will generate patient- specific disease variants in iPS cells matched to corresponding animal models. The RSS with the Bioinformatic Section (BIS) will analyze transcriptional profile changes associated with the variant, predict interacting drugs, and then rapidly begin validating and screening the iPS cells with potential therapeutics. The RSS will be poised to compare these cell line and drug testing results directly to animal model phenotyping and therapeutics data. The RSS is a bridge between all other components in CPAM and outside investigators to promote use of CPAM resources. Importantly, the RSS provides access to enhanced services that are difficult to accomplish in most individual labs and are not readily available through other mechanisms or are prohibitively costly in terms of expense and/or time impediments. Our team is composed of animal model and drug testing experts in a variety of areas (ciliopathies, Rasopathies, neurodevelopmental/degenerative disorders, birth defects, cancer, and musculoskeletal/neuromuscular disorders). Hence, at a minimum, we can provide specialized services in these broad areas leading towards both improved models that phenocopy human disease and novel therapeutics evaluated at a fraction of traditional drug screening efforts. We facilitate high level, scientific dialogues between CPAM and external and internal investigators and provide validated models allowing for phenotype assessment in collaboration with the DMU and the Pre/Co-clinical Section (PCS). The goal of these conversations is to foster new collaborations resulting in detailed secondary/advanced phenotyping through UAB Core Resource facilities that validate variant pathogenicity (in cell or animal models), provide new biological insights, and promote effective targeted therapeutics testing of the models generated by the CPAM pipeline.