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
Recent Selected Grantee Publications
Small-Diameter Artery Grafts Engineered from Pluripotent Stem Cells Maintain 100% Patency in an Allogeneic Rhesus Macaque Model
Zhang et al., Cell Reports Medicine. 2025.
Globally, the leading cause of death is occlusive arterial disease, but surgical revascularization improves patient prognosis and reduces mortality. Vascular grafts often are needed in coronary…
Differentiation Success of Reprogrammed Cells Is Heterogeneous In Vivo and Modulated by Somatic Cell Identity Memory
Zikmund et al., Stem Cell Reports. 2025.
Nuclear reprogramming can change cellular fates, yet reprogramming efficiency is low, and the resulting cell types are often not functional. Researchers used nuclear transfer to Xenopus eggs to…
Local Tissue Response to a C-X-C Motif Chemokine Ligand 12 Therapy for Fecal Incontinence in a Rabbit Model
Ruetten et al., American Journal of Physiology—Gastrointestinal and Liver Physiology. 2025.
Obstetric anal sphincter injury (OASI) occurs in 2–7% of vaginal childbirths. Surgical interventions for OASI are suboptimal, with 30% of women reporting continued reduction in quality of life due to…