Programs and Activities Highlights
- Specialized Research Training in Animal Models and Related Resources: Focus Group, Session 1
ORIP held a series of focus groups involving veterinary trainees, early-career scientists, mentors, and training program directors to identify and cultivate opportunities for collaborations and partnerships that address challenges and synergize strategies and resources supporting recruitment and retention of veterinary scientists. In the first session, held April 11, 2025, selected training program directors and mentors in the ORIP T32 program were invited to discuss the challenges and opportunities that exist in the current program.
- K01 Special Emphasis Research Career Award (SERCA) Guidelines
In April 2025, ORIP updated its K01 SERCA guidelines with new language covering updated ORIP priorities, including new approach methodologies (NAMs) for complementing animal research relevant to human health and diseases. The SERCA is intended to stimulate the development of veterinary scientists with interests in comparative medicine and related research questions.
- ORIP and National Eye Institute Training Programs
Training Program Directors from ORIP and the National Eye Institute met on September 16, 2024, to compare their training program outcomes and future strategies. ORIP's Division of Comparative Medicine offers career development support for individuals with D.V.M. or Ph.D. degrees, as well as predoctoral veterinary students.
- T32 and T35 Directors' Consortium
A meeting of the T32 and T35 Directors’ Consortium was held on September 16, 2024. ORIP staff presented on program and grant topics to the T32/T35 directors, and NIH updates to training grant applications were discussed.
- NIH Loan Repayment Program
ORIP revised its Loan Repayment Program guidelines with new language covering updated ORIP priorities. Specifically, proposed research investigations must be applicable to the interests of two or more of the categorical NIH institutes and centers (ICs). In addition, projects that predominantly address the research interests of one NIH IC, but that are peripherally related to the research interests of other ICs, will not be considered appropriate. Extramural Loan Repayment Programs provide for the repayment of educational loan debt up to $50,000 annually for qualified health professionals performing research within the mission of NIH and supported by domestic, nonprofit, or government entities.
Read more in the archive.
ORIP-Supported Research Highlights
- Activated Polyreactive B Cells Are Clonally Expanded in Autoantibody Positive and Patients with Recent-Onset Type 1 Diabetes
Patients who are prediabetic do not have symptoms but do have autoantibodies (cells that target a normal molecule in the body) present. However, it remains largely unknown how autoreactive B cells affect the development of Type 1 diabetes (T1D). Researchers isolated B cells from the blood of patients with T1D, patients who were prediabetic (AAB), and relatives who were not diabetic and not autoreactive. Results showed that B cells from AAB and T1D patients have altered gene expression in cell signaling and inflammation pathways. These results provide a foundation for future studies focused on identifying biomarkers or creating cell-targeted treatments for T1D.
- From In Vitro Development to Accessible Luminal Interface of Neonatal Bovine-Derived Intestinal Organoids
Diarrhea caused by infectious agents in the intestine of newborns remains a major human health concern. Three-dimensional (3D) culture techniques of intestinal epithelial cells have been developed to study host–pathogen interactions as new approach methodologies (NAMs) that complement animal research. With these methods, primary intestinal stem cells from donor intestinal crypts are cultured within an extracellular matrix, which supports the self-organization of the multipotent cells into 3D structures known as intestinal organoids. In this study, the team developed intestinal organoids and organoid-derived single-layer cell cultures to enable research on early-life intestinal function and disease. These organoids captured key aspects of the gastrointestinal lining, how it functions, and the unique roles of different cell types. These models replicate the in vivo intestinal epithelium through their multicellularity, self-replication, and differentiation into mature epithelial cell types and provide a complementary platform for studying human health and disease.
- Alterations in Tumor Aggression Following Androgen Receptor Signaling Restoration in Canine Prostate Cancer Cell Lines
Prostate cancer (PCa) ranks second worldwide in cancer-related mortality, but only a few animal models exhibit naturally occurring PCa that recapitulates the symptoms of the disease. Neutered dogs have an increased risk of PCa and often lack androgen receptor (AR) signaling, which is involved in upregulating tumorigenesis but can also suppress aggressive cell growth. In this study, researchers sought to understand more about the role of AR signaling in canine PCa initiation and progression by restoring AR in canine PCa cell lines and treating them with dihydrotestosterone. One cell line exhibited AR-mediated tumor suppression; one cell line showed altered proliferation (but not migration or invasion); and a third cell line exhibited AR-mediated alterations in migration and invasion (but not proliferation). The study highlights the heterogeneous nature of PCa in dogs and humans but suggests that AR signaling might have therapeutic potential under certain conditions.
- A Review of CD4+ T Cell Differentiation and Diversity in Dogs
CD4+ T cells are an important component of both the adaptive immune response and immune maintenance. They carry out many functions and can differentiate into numerous specialized subsets, including T helper type 1 (TH1), TH2, TH9, TH17, TH22, regulatory T cells, and follicular T helper cells. CD4+ T cells also have a capacity for long-term immunological memory and rapid reactivation upon secondary exposure. However, our understanding of the role of CD4+ T cells in immune response is largely based on studies in mice, humans, and, to a lesser extent, pigs. Comparatively, our understanding of CD4+ T cells in canines is much less complete. This review summarizes the current understanding of canine CD4+ T cells from a comparative perspective by highlighting both the similarities and differences from mouse, human, and pig CD4+ T-cell biology.
- A Novel TGFβ Receptor Inhibitor, IPW-5371, Prevents Diet-Induced Hepatic Steatosis and Insulin Resistance in Irradiated Mice
Radiation damages adipose progenitor cells and increases liver fibrosis, leading to the development of metabolic-associated fatty liver disease (MAFLD) and insulin resistance. As the number of cancer survivors increases and the risk of accidental radiation exposure rises, there is a pressing need to characterize and mitigate the delayed effects of radiation exposure. Some of these effects are mediated by TGFβ pathway signaling, which increases in response to radiation exposure and causes fibrosis. In this study, IPW-5371—a small-molecule inhibitor of a TGFβ receptor called activin receptor-like kinase 5 (ALK5)—was shown to protect mice from the effects of sublethal whole-body irradiation and chronic consumption of a Western diet. Male and female mice treated with IPW-5371 exhibited lower fibrosis and fat accumulation in the liver, were more responsive to insulin, and had lower circulating triglycerides and better muscle endurance. IPW-5371 is a promising treatment for mitigating the metabolic effects of radiation exposure and preventing MAFLD.
Read more in the archive.
