Precision Disease Modeling
In fiscal year 2015, ORIP launched the Pilot Centers for Precision Disease Modeling Initiative (PAR-14-280), funding three U54 Centers. The purpose of the program was to provide the biomedical community with advanced animal models needed to develop precision therapies for monogenic and complex disorders. Given the success of the initial cohort (see Archives), ORIP renewed the Pilot Centers for Precision Disease Modeling Initiative in 2020 (PAR-20-085) by awarding three new U54 Centers. The program was revised to increase focus on creating pipelines for research community-nominated unique human genomic variants linked to diseases for cost-effective high-throughput testing in such models as mouse, rat, C. elegans, zebrafish, Drosophila, Xenopus embryos, and human induced pluripotent stem cells, or iPSCs. The diseases modeled include ciliopathy; rasopathy; cohesinopathy; Marfan's syndrome and Ehlers-Danlos syndrome; macular degeneration; and musculoskeletal, cardiovascular, and neurodevelopmental defects. After validation of the expected gene editing, the new Centers will be establishing assays to conduct comprehensive functional and phenotypic analysis to evaluate disease-causing variants. The Centers are working to ascertain the relevance of these animal models to the molecular, cellular, pathophysiological, and/or phenotypic characteristics observed in the patient to improve the biological understanding of disease mechanisms, develop diagnostic tools, and test targeted or repurposed therapeutics. As was the case with the previous program, the creation and distribution of precision animal model resources and related services will continue to be a core function for these Centers.
BCM Center for Precision Medicine Models
U54OD030165
Jason D. Heaney, Ph.D., Brendan Lee, Ph.D., Aleksandar Milosavljevic, Ph.D.
Baylor College of Medicine
Center for Precision Medicine Models
The Jackson Laboratory Center for Precision Genetics
U54OD030187
Cathleen M. Lutz, Ph.D., Stephen Murray, Ph.D.
The Jackson Laboratory, Bar Harbor, ME
JAX Center for Precision Genetics
UAB Pilot Center for Precision Animal Modeling (C-PAM)
U54OD030167
Bradley K. Yoder Ph.D., Matthew B. Might, Ph.D.
University of Alabama at Birmingham
Center for Precision Animal Modeling (C-PAM)
Archives
Information on the Initial Cohort
In fiscal year 2015, ORIP launched the Pilot Centers for Precision Disease Modeling Initiative (PAR-14-280), funding three U54 Centers. The purpose of the program was to provide the biomedical community with advanced animal models needed to develop precision therapies for monogenic and complex disorders. Each Center consisted of an interdisciplinary research team of scientists and physicians organized to address specific medical problems by creating new animal models to more precisely mimic patient-specific disease processes and to develop innovative treatment options. Current technology permits specific genetic modifications in model animal species, as well as the ability to replace specific cells and tissues, resulting in phenotypes that are closely analogous to human patients. These new animal models will accelerate the generation of precision diagnostic and therapeutic approaches for such diseases as cancer, Parkinson’s disease, and diabetes. These three Centers have improved methods and technologies to rapidly model disease-specific genomic alterations. The techniques that have been developed include robust phenotyping to determine if specific genetic changes recapitulate a human phenotype, creating and validating numerous animal models in different animal species, conducting a wide range of studies that increase the understanding of how gene mutations influence cellular and organismal phenotypes, and large numbers of preclinical studies using assisted precision-directed therapies. Overall, the three Centers have published more than 100 research articles as of 2020 and have collaborated on numerous projects across the nation.
A New Disease Platform Leveraging Complex Drosophila and Mammalian Models
U54OD020353
Ross L. Cagan, Ph.D.
Center for Personalized Cancer Therapeutics
The Mount Sinai Hospital, New York, NY
Mount Sinai Pilot Center for Precision Disease Modeling
The Jackson Laboratory Center for Precision Genetics: From New Models to Novel Therapeutics
U54OD020351
Robert W. Burgess, Ph.D.
The Jackson Laboratory, Bar Harbor, ME
JAX Center for Precision Genetics
MSKCC Pilot Center for Precision Disease Modeling
U54OD020355
Scott W. Lowe, Ph.D.
Memorial Sloan-Kettering Cancer Center, New York, NY
Pilot Center for Precision Disease Modeling
Related Research Highlights
Recent Selected Grantee Publications
Monitoring Fetal Somatic Cell Genome Editing In Vivo with Total-Body Positron Emission Tomography: Studies in Rhesus Macaques (Macaca mulatta)
Tarantal et al., Human Gene Therapy. 2026.
Gene-editing tools—such as somatic cell genome editing—must be validated to ensure that in utero (in the womb) therapies for inherited disorders are safe and effective. Using 6- to 11‑year-old…
A Universal 6iL/E4 Culture System for Deriving and Maintaining Embryonic Stem Cells Across Mammalian Species
Wang et al., Cell Research. 2026.
Embryonic stem cells (ESCs) can become many different types of cells during embryonic development. Obtaining ESCs from embryos remains a challenge for biomedical research. In this study, researchers…
A Thymus-Independent Artificial Organoid System Supports Complete Thymopoiesis from Rhesus Macaque-Derived Hematopoietic Stem and Progenitor Cells
Wilde et al., Biomedicines. 2025.
The creation of T cells within the body involves many steps that begin with T cell progenitor cells (cells that become T cells) in the bone marrow. T cells finish developing and multiply in the…