Programs and Activities Highlights
- 2026 Meeting of the Centers for Precision Disease Modeling Consortium
ORIP organized and conducted the annual meeting of the Centers for Precision Disease Modeling Consortium on June 4, 2026. The consortium was established to provide the biomedical community with advanced models needed to develop precision therapies for monogenic and complex disorders. Meeting participants included ORIP staff, principal investigators, and team representatives.
- ORIP Workshop: Advancing Research Infrastructure to Study Human Diseases
The Advancing Research Infrastructure to Study Human Diseases workshop was held on June 8 and 12, 2026. The workshop offered a platform to discuss complementary approaches to addressing complex biological mechanistic questions related to expanding NIH-funded model resources and physical infrastructure, validating new approach methodologies (NAMs), and improving the predictability and scalability of models for human diseases. Day 1 of the workshop addressed the strategic and translational integration of NAMs and animal models in biomedical research. Day 2 of the workshop focused on presenting emerging NAMs technologies that will advance human disease research, with an emphasis on strategies for integrating and validating combinatorial NAMs. A meeting report and video recording will be posted on the ORIP website at a later date.
- INCLUDE Project: Transformative Research Awards for Down Syndrome (R01 Clinical Trial Not Allowed)
The NIH INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project seeks to improve the health and quality of life for individuals with Down syndrome. ORIP has signed onto this notice of funding opportunity, which invites researchers to submit applications for supporting groundbreaking, exceptionally innovative, original, and/or unconventional research that has the potential to create new scientific paradigms, establish entirely new and improved clinical approaches, or develop transformative technologies related to Down syndrome.
- Access to Genetically Engineered Mouse Resources
During the 22nd Workshop on the Pathology of Mouse Models for Human Disease, an ORIP staff member presented on access to genetically engineered mouse resources. The workshop was held both virtually and in person from April 20–24, 2026, at St. Jude Children’s Research Hospital in Memphis, Tennessee.
- ORIP Workshop: Cryopreservation and Other Preservation Approaches for Animal Models
The final session of the Cryopreservation and Other Preservation Approaches for Animal Models Workshop was held virtually on April 27, 2026. The session addressed cryopreservation and other methods for swine models in biomedical research. During the discussion, the workshop presenters and participants identified needs related to facility infrastructure and regional hubs, animal maintenance, technology advancements, automation strategies, protocol optimization, reagent creation, and training opportunities. A report will be available on the ORIP website at a later date.
Read more in the archive.
ORIP-Supported Research Highlights
- Environmental and Developmental Factors Shape Anti-AAV Immunity in Pigs
Adeno-associated viruses (AAVs) show promise for delivering gene therapies to treat monogenic (caused by changes in a single gene) diseases. Researchers evaluated the utility of pigs (sex not stated) as models for testing AAV-based therapies. Consistent with previous studies, they showed that pigs naturally produce antibodies (protective proteins made by the immune system) that can block AAV vectors. These antibodies appeared by 2 weeks of age and increased over time. Immune responses also varied by environment, with pigs in standard housing showing stronger and more diverse responses than those in highly controlled settings. Removing IgG (a type of antibody found in blood and extracellular fluid) restored AAV activity in laboratory tests. This study suggests that pigs can help researchers test ways to overcome immune barriers associated with gene therapies.
- Genome-Wide Association Mapping and Targeted Loss of Function Studies Identify Shroom3 as a Driver of Hyperpolyploidy and Ventricular Dilation
Cardiomyocyte polyploidy (a condition where heart muscle cells replicate their DNA but fail to divide) is associated with responses to cardiac injury, but researchers do not fully understand the mechanisms explaining this effect. Researchers studied heart muscle cells in rats (both sexes used) and found that cells with extra chromosome copies were linked to weaker heart pumping and enlarged heart chambers. By scanning rat genomes, they identified the gene Shroom3 as an important driver of this process. When Shroom3 was disrupted in heart cells, polyploidy increased and heart function worsened. The findings suggest Shroom3 helps control heart cell structure and may offer clues for understanding heart disease.
- ABL Kinases Regulate FGF Signaling Independent of CRK Phosphorylation to Prevent Peters Anomaly Type II
Peters anomaly is a developmental disorder of the front of the eye. It is one of the most common causes of babies being born with vision issues, including a cloudy cornea (the transparent lens that covers and protects the eye). Using male and female mouse models for Peters anomaly, researchers found that removing molecules known as ABL kinases can restore lens formation when FGF cell signaling is missing. However, results also showed that deleting ABL kinases causes Peters anomaly type II through a pathway that does not rely on ERK signaling. This defect was corrected when target molecules—CRK and CRKL—were reduced. This study found a signaling pathway, ABL-PTPN12-p130CAS, that controls the mechanical forces needed for the lens vesicle to separate properly during eye development. These findings highlight a new signaling pathway that could be targeted in treatment strategies for Peters anomaly type II.
- Deep Single-Cell Decoding of Human Pancreatic Islets Reveals T2D β-cell Gene Expression Defects
Pancreatic islets are clusters of cells in the pancreas that secrete hormones—including insulin—to maintain glucose (blood sugar) levels. Pancreatic islets play a key role in type 2 diabetes (T2D) development. However, the T2D-specific genetic changes seen in different cell types of pancreatic islets remains poorly understood. In this study, researchers collected nearly 250,000 pancreatic islet cells from male and female non-diabetic, pre-diabetic, and T2D patients to better understand specific cell-type changes in T2D disease conditions. Results showed that patients with T2D had fewer insulin-producing β-cells that functioned properly and more senescent (cells that no longer divide into new cells) β-cells. Results also found hundreds of genes with altered activity—including genes linked to vitamin A metabolism and nerve-like signaling. Combining human and T2D mouse model data found several genes, such as PDZK1 and GRAMD2B, that play an important role in keeping β-cells healthy and causing T2D disease when abnormal. These findings can help guide future treatments for T2D.
- Improve Genetic Quality Control to Increase Rigor and Reproducibility of Mouse Research
Inaccurate genetic descriptions of laboratory mouse strains can affect experimental design, data analysis, rigor, and reproducibility. In this study, researchers genotyped (assay to identify the entire set of genes) 611 samples from 341 Mutant Mouse Resource and Research Centers (MMRRC) strains (sex not stated). Results found inconsistencies in about half of the samples. The researchers used state-of-the-art tools to develop a genetic quality control process for mouse strains that uses clear metrics to classify the strains accurately. This quality control workflow validates alleles (different versions of a gene), estimates genome (complete collection of DNA) replicability, and flags issues with naming or gene constructs. This study improves confidence in mouse model–based research, increases reproducibility, strengthens grant and publication standards, and enhances the rigor of animal-model resources.
Read more in the archive.
