Programs and Activities Highlights
- Ruth L. Kirschstein National Research Service Award (NRSA) Institutional Research Training Grant (Parent T32)
ORIP released two institutional training awards—Animal Model Research for Veterinarians (2T32OD028239-06A1) and Comparative Biomedical Research Training for Veterinarians (2T32OD011083-16)—in June 2026 to strengthen the pipeline of veterinary scientists contributing to biomedical research. These awards support structured research training for veterinarians in such areas as research model development, translational research, new approach methodologies, and rigorous experimental design, equipping trainees with the skills needed to address human health challenges. By investing in veterinary scientist research training programs, ORIP advances the NIH mission of seeking fundamental knowledge about living systems and applying that knowledge to enhance health, lengthen life, and reduce illness and disability, while also ensuring a highly skilled workforce capable of supporting high-quality and reproducible biomedical research. - Human Tissues and Organs for Research Resource Pilot Award
An ORIP Special Emphasis Research Career Award (SERCA) K01 awardee received a pilot award through the Human Tissues and Organs for Research Resource (HTORR). Launched in 2024, the Pilot Award Program, a component of the ORIP-supported supported HTORR program, supports early-stage investigators by providing up to ten biological specimens to facilitate completion of pilot studies and collection of preliminary data necessary to obtain subsequent funding. This pilot award will allow Dr. Yoko Ambrosini, an ORIP SERCA K01 awardee, to incorporate human new approach methodologies into her research on epithelial–immune–microbial crosstalk in the gut–brain axis of inflammatory bowel disease. - National Association of Veterinary Scientists D.V.M./Ph.D. Colloquium
An ORIP staff member presented a keynote talk, titled “NIH Funding Opportunities for Veterinarian-Scientists,” at the National Association of Veterinary Scientists D.V.M./Ph.D. Colloquium in August 2025. An ORIP staff member also served as a panelist at the D.V.M./Ph.D. Alumni Panel during this meeting. - Specialized Research Training in Animal Models and Related Resources: Focus Group, Session 2
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 second session, held May 15, 2025, selected current trainees supported by ORIP T32 grants were invited to discuss the challenges and opportunities that exist in the current program. Additionally, early-career scientists—including ORIP K01 awardees, applicants, and graduates of the T32 program—were invited to discuss challenges faced by early-career scientists. - T32 and T35 Directors Consortium
The T32 and T35 Directors Consortium was convened on June 2, 2025. ORIP staff presented the latest NIH policies during the meeting. ORIP offers Institutional Research Training Grants through the T32 and T35 mechanisms to encourage veterinarians to consider a career in biomedical research.
Read more in the archive.
ORIP-Supported Research Highlights
- Adult Canine Pancreatic Organoids Enable Functional Analysis of Pancreatic Epithelial Barrier and Inflammatory Responses
3D organoids are useful for modeling pancreatic epithelial development, differentiation, and disease. Dogs naturally develop a range of pancreatic diseases—including acute pancreatitis and pancreatic cancer—that mimic the clinical and pathological (disease-causing) features observed in humans. In this study, researchers successfully developed a long-term organoid model for the pancreas from 1.5- to 10-year-old male adult canines that demonstrated a stable ductal phenotype (physical characteristics). The researchers also developed a 2D culture from the organoids and showed that epithelial barrier integrity and function were maintained. This study provides a reproducible protocol for creating ethically accessible and physiologically relevant 3D organoids and 2D cultures of the adult pancreas. This study provides a foundation for future research in pancreatic disease modeling, comparative medicine, and therapeutic strategies. - Cognitive Impairment Caused by Compromised Hepatic Ketogenesis Is Prevented by Endurance Exercise
Previous research has demonstrated that endurance exercise improves cognition and is neuroprotective against aging and disease. However, the underlying mechanisms of these benefits remain poorly understood. In this study, researchers determined whether ketones, produced by the liver, mediate endurance exercise–based neuroprotection. Using 6-month-old female rats, researchers found that hepatic ketogenesis (production of ketones by the liver) is required to maintain cognition, synaptic plasticity (connections across brain cells), and mitochondrial (cellular organelles that create energy) function. Results also showed that prolonged endurance exercise prevents nervous system deficiencies caused by insufficient hepatic ketogenesis. These findings establish a link between the liver and brain and demonstrate the importance of understanding how peripheral tissue, such as the liver, regulates brain health. - T‐Cell Signaling Pathways, Including Exhaustion, Predominate in Unhealthy Visceral and Subcutaneous Adipose Tissues
Adipose tissue (fat) and adipose inflammation—caused by immune cells—are implicated in metabolic (all changes in a cell to produce energy and molecules) health. Previous research shows that visceral (surrounding organs) adipose tissue (VAT) generally is a factor of poor metabolic health, whereas subcutaneous (found under the skin) adipose tissue (SAT) is considered protective. Metabolic syndrome spectrum (MetS) is obesity with a range of risk factors involved in other metabolic conditions—including diabetes. The role of VAT and SAT across the MetS remains poorly understood. Using a 6- to 23-year-old nonhuman primate (sex not stated) model for MetS, researchers found that T-cell signaling—specifically T-cell exhaustion—is a major characteristic of poor metabolic health related to both VAT and SAT. These findings provide new insights into the importance of the adaptive immune system—such as T cells—in unhealthy adipose tissue linked to metabolic diseases. - Therapeutic Delivery of Albumin-Binding siRNA Targeting IRS2 to Diverse Cell Types Reduces Mammary Tumor Growth
Aggressive subtypes of breast cancer remain difficult to treat with current therapies. A new type of drug, oligonucleotide (short chains of DNA or RNA) therapies, modifies gene expression in cancer cells, hindering the formation of proteins within the cells that drive cancer progression. Efficient delivery of oligonucleotides, such as small interfering RNAs (siRNAs), remains a challenge for this class of drugs. Researchers chemically modified siRNAs to bind to an albumin-binding dendrimer (molecules that interact with albumin, a transportation protein found in blood). Using female human and mouse cell cultures, researchers identified siRNAs that target IRS2, a signaling protein involved in triple-negative breast cancer (TNBC). Using a 7- to 9‑week-old female mouse model for TNBC, researchers found that the siRNA reduced IRS2 expression in tumor and stromal cells (cells that create connective tissue for structural support). Results also showed that tumor growth was reduced, vascularization (embedding of blood vessels into the tumor) was decreased, and macrophage phenotypes (physical characteristics) were altered. These findings support the use of siRNAs to target different cell populations within breast tumors and to inhibit a key driver of breast cancer. - Deletion of Ptpn2 in B Cells Promotes Autoimmunity via TLR and JAK/STAT Signaling
Autoimmunity occurs when adaptive immune cells—T cells and B cells—mistake healthy tissue as a foreign object to attack. Previous data from patients with young-onset autoimmunity highlight the importance of PTPN2 in the development of autoimmunity and PTPN2-mediated autoimmunity in T cells. However, the role of PTPN2 in causing B cell–mediated autoimmunity remains poorly understood. Using a 24- to 26-week-old mouse model with Ptpn2 deleted in B cells (both sexes used), researchers found that inflammation, frequency of autoimmune-associated B cells (ABCs), and circulating autoantibodies were increased. Results also showed that Ptpn2 negatively regulates several signaling pathways in B cells involved in creating ABCs. These findings highlight the importance of Ptpn2 in preventing B cell–mediated autoimmunity. - Rhesus Macaques with an OPA1 Mutation Demonstrate Features of Autosomal Dominant Optic Atrophy
Autosomal dominant (a disease that is caused by a single mutated copy of a gene) optic atrophy (ADOA) is an inherited optic nerve disease that causes vision loss. ADOA is caused by mutations in the gene OPA1, and therapies for ADOA are limited. Using a 4-month-old to 29-year-old spontaneous nonhuman primate (NHP) model for ADOA (both sexes used), researchers observed retinal nerve fiber (tissue lining the back of the eye) thinning and abnormal mitochondrial (organelles in cells that produce energy) function in retina cells. The NHP model for ADOA also showed a broad range of phenotypes (physical characteristics) that mimic the clinical variability seen in patients with ADOA. These findings highlight the use of the NHP model for ADOA to test new therapies that may benefit patients. - Single-Cell Morphodynamical Trajectories Enable Prediction of Gene Expression Accompanying Cell State Change
Extracellular signals (signals from outside the cell) can alter pathways within the cell, which leads to changes in the cell’s phenotype (physical characteristics). The connection between the molecular pathways within the cell that cause phenotypic changes—such as motility and morphology—remains poorly understood. Using female human cell lines isolated from breast disease tissue, researchers captured imaging and transcriptomics (all RNA molecules expressed in a cell) data over time for single cells and developed data-driven models to map connections. The researchers called this approach the molecular and morphodynamics-integrated single-cell trajectories (MMIST). Results showed that MMIST predicted gene expression profiles that were caused by specific extracellular signals and associated with reversible changes in a cell’s phenotype (epithelial-mesenchymal transition and mesenchymal-epithelial transition). The MMIST model provides a foundation for understanding the transition of a cell’s phenotype to develop therapies that inhibit these changes. The model also could be developed further to include more cell phenotypes to extend its use to more tissues and pathological (disease-causing) states.
Read more in the archive.
