Programs and Activities Highlights
- 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.
- INCLUDE Project: Exploratory/Developmental Research Awards for Down Syndrome (R21 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 new exploratory and developmental research projects that address critical needs for Down syndrome projects, as articulated in the INCLUDE Project objectives.
- Notice of Funding Opportunity: Animal and Biological Material Resource Centers (P40 Clinical Trial Not Allowed)
This notice of funding opportunity (NOFO) encourages grant applications for Animal and Biological Material Resource Centers. These centers provide support for special colonies of laboratory animals and associated services, as well as other resources, such as informatics tools, reagents, cultures (cells, tissues, and organs), and genetic stocks that serve the biomedical research community in a variety of research areas on a local, regional, and national basis. Of special interest is a requirement for the Center to closely coordinate with efforts to develop new approach methodologies (NAMs) that complement traditional animal-based research. The Applied Research Component of the project should include studies to generate comparative data to increase applicability of NAMs and promote integration of the most predictive human disease models. The goal of projects supported by this NOFO is to provide research resources that facilitate the optimization and enhancement of scientific rigor, transparency, and experimental reproducibility of biomedical research. Proposed Animal and Biological Material Resource Centers must have broad application to multiple NIH institutes or centers (ICs) to align with ORIP’s NIH-wide mission.
Read more in the archive.
ORIP-Supported Research Highlights
- 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.
- NHP-specific NAMs Directly Supplement the Pre-clinical Interventional Study
People with HIV live with chronic inflammation, which impairs the thymus (an organ that makes immune cells). T cells develop and multiply in the thymus, and researchers need a new approach methodology (NAM)—a way to do research without relying on a whole organism—to study T cells during disease. Wilde et al. created the Rhesus Artificial Thymic Organoid (RhATO)—a 3D nonhuman primate (NHP)–specific cell culture that models key stages of T-cell development. Researchers tracked the potential for T-cell development from pre-thymic bone marrow progenitors (cells that become T cells) over time. Anwar et al. applied this platform to simian immunodeficiency virus (SIV), the NHP equivalent of HIV. They found that SIV-associated inflammation—particularly a specific inflammatory molecule known as IL-6—restricts progenitor cells from becoming T cells; this process plays a direct role in the loss of viral control. This NHP-specific NAM—when combined with in vivo (in a living organism) preclinical NHP studies—addresses how anti-inflammatory treatment strategies reshape the potential of progenitor cells to become T cells; these mechanistic findings can be translated to people with HIV. This integrative experimental framework would not be possible without NHP-specific NAMs, highlighting that they are not redundant with human NAMs but rather serve as essential translational platforms that bridge preclinical and clinical HIV studies.
- Generation of a Rhesus Macaque Harboring a Multivalent Reporter for Assessing Gene Editing Outcomes
Preclinical animal models that measure on-target delivery and off-target editing are needed to develop safe and effective therapies. In this study, researchers developed a rhesus macaque preclinical model (sex not stated) that carries a fluorescent reporter system, BETLE, that is designed to help test whether gene-editing therapies reach the right cells and avoid off-target, unintended edits. Zygotes (the cell created from the fertilization of an egg cell with a sperm cell) were microinjected with piggyBac transposase (a protein that relocates DNA segments to other DNA regions) to create preimplantation embryos that resulted in healthy transgenic rhesus macaques (primates with DNA from another source added to their DNA). Results showed that only 5–8% of cells had successfully integrated BETLE. These findings offer important lessons learned to improve future transgenic primate preclinical model creation.
Read more in the archive.
