Selected Grantee Publications
- 608 results found
Transplantation of Human Kidney Organoids Elicited a Robust Allogeneic Response in a Humanized Mouse Model
Mon-Wei Yu et al., Kidney International. 2025.
https://pubmed.ncbi.nlm.nih.gov/40127865
Organoids are 3D cell cultures that contain several cell types and mimic organ function. Kidney organoids are helping advance studies focused on kidney diseases. However, the use of kidney organoids in studies on tissue transplanted from one organism into another is not well explored. Researchers used a unique humanized NSG-BLT mouse model (sex not specified), which contains a human immune system. Following the transplantation of kidney organoids into the humanized NSG-BLT mice, researchers looked at the immune response at days 20 and 30. Results showed that transplantation of kidney organoids caused infiltration of immune cells, production of cytokines (molecules secreted by immune cells), and an increase in the number of T cells. This study provides a novel platform for bridging the gap between mouse and human studies, which may speed up drug development to reduce tissue rejection in organ transplants. Supported by ORIP (R24OD036199), NCATS, NCI, NIAID, and NIDDK.
SIV Proviruses Seeded Later in Infection Are Harbored in Short-Lived CD4+ T Cells
Sambaturu et al., Cell Reports. 2025.
https://pubmed.ncbi.nlm.nih.gov/40327506
HIV can stay dormant for years by integrating its genetic materials into host immune cells, creating a persistent reservoir that is difficult to remove. It remains unclear which HIV-infected cells survive long term. This study used samples from simian immunodeficiency virus (SIV)–infected macaques (sex not specified) to examine how and when virus-infected cells become part of the long-lived reservoir. Researchers discovered that newer viral sequences were found in short-lived CD4+ T cells, and long-lived cells contained older, more genetically varied viruses. These results suggest that viruses from early infection persist in the long term, whereas newer infections remain in cells that turn over rapidly, providing important insights on future HIV cure strategies. Supported by ORIP (R01OD011095) and NIAID.
The Saponin Monophosphoryl Lipid A Nanoparticle Adjuvant Induces Dose-Dependent HIV Vaccine Responses in Nonhuman Primates
Ramezani-Rad et al., The Journal of Clinical Investigation. 2025.
https://pubmed.ncbi.nlm.nih.gov/40036068
Researchers tested an HIV vaccine booster using a nanoparticle-based adjuvant (an ingredient that helps vaccines work better) called saponin monophosphoryl lipid A nanoparticle (SMNP). Using male and female nonhuman primates, researchers found that higher doses of SMNP triggered stronger immune responses, including robust B-cell activation and the production of two neutralizing antibodies that are important for durable protection. Notably, only high-dose groups showed significant levels of these antibodies. Findings highlight the importance of dose-dependent potency of vaccine in shaping immune responses. This study suggests SMNP’s potential for use in humans as a next-generation vaccine. Supported by ORIP (P51OD011107, S10OD025052) and NIAID.
Real-Time SPR Biosensing to Detect and Characterize Fast Dissociation Rate Binding Interactions Missed by Endpoint Detection and Implications for Off-Target Toxicity Screening
Martelly et al., Biomolecules. 2025.
https://pubmed.ncbi.nlm.nih.gov/40563522
Accurate detection of interactions among molecules is essential for basic, translational, and clinical research—including the identification of biomarkers, development of therapies, and discovery of underlying biological processes. A false negative result means that a condition is indicated as absent when it is actually present. A false negative result is more likely to occur when researchers require only a single endpoint in experiments with molecular interactions that have fast binding kinetics (quick reaction rates among molecules). Real-time detection methods, such as surface plasmon resonance (SPR), allow researchers to study the assembly and disassembly of molecular interactions with fast binding kinetics. Researchers compared the fluorescence endpoint assay (a traditional single-endpoint method) to real-time sensor-integrated proteome-on-chip SPR-based detection. The results highlight the limitations of the fluorescence endpoint assay when investigating transient interactions characterized by fast dissociation rates. Supported by ORIP (R43OD024970) and NCATS.
From In Vitro Development to Accessible Luminal Interface of Neonatal Bovine-Derived Intestinal Organoids
Dykstra et al., BMC Veterinary Research. 2025.
https://pubmed.ncbi.nlm.nih.gov/40325425
Organoids are 3D cell cultures that contain several cell types and mimic specific functions of an organ. Intestinal organoids provide functionally relevant models that bridge the gap between standard single-layer cell cultures and animal model studies. Diarrhea in newborn calves remains a major health concern in agriculture, and age-relevant models to study disease mechanisms and progression are unavailable. Host–pathogen interactions vary with developmental stage, requiring cell cultures that reflect the distinct biology of the newborn gut. In this study, the team developed intestinal organoids and organoid-derived single-layer cell cultures from 14-day-old dairy calves to enable research on early-life intestinal function and disease. These organoids captured key aspects of the gastrointestinal lining, how it works, and the unique functions of different cell types. Future work will focus on adapting single-layer cell culture methods for additional gut regions. Supported by ORIP (K01OD030515).
Void Spot Assay Visualization Optimization for Use of Void Whizzard in Rats (Rattus norvegicus)
Ruetten et al., Physiological Reports. 2025.
https://pubmed.ncbi.nlm.nih.gov/40323208
A void spot assay (VSA) noninvasively evaluates bladder function by analyzing urine on laboratory paper. This study improves VSA by comparing paper imaging techniques: bright field light (BF), ultraviolet light (UV), and ninhydrin spray (N). All three groups significantly differed in overall urine spot count. BF visualization proved difficult. N visualization provided an ideal way to highlight urine and capture an image with a digital camera. Human fingerprints from pre-assay handling of paper interfered with the analysis of the smallest sized spots. No differences were found in the detection of larger spots, spot distribution, or overall spot area. This study will help scientists develop a standardized VSA protocol for assessing bladder function in rodent models. Supported by ORIP (T32OD010957) and NIDDK.
Activated Polyreactive B cells are Clonally Expanded in Autoantibody Positive and Patients With Recent-Onset Type 1 Diabetes
Nicholas et al., Cell Reports. 2025.
https://pubmed.ncbi.nlm.nih.gov/40117290
Type 1 diabetes (T1D) develops from a sustained attack on the pancreas’ insulin-producing cells by the body’s immune system. Previous research has emphasized the role of autoreactive (acting against a person’s own tissues) T cells in T1D disease progression. Patients who are prediabetic do not have symptoms but do have autoantibodies (immune proteins that target a normal molecule in the body) present. However, it remains largely unknown how autoreactive B cells affect the development of T1D. Researchers isolated B cells from the blood of patients with T1D, patients who were prediabetic (AAB), and relatives who were nondiabetic and not autoreactive. Results showed that B cells from AAB and T1D patients have altered gene expression in cell signaling, antigen-presentation (what tells your immune system whether something is harmful), and inflammation pathways. These results provide a foundation for future studies focused on identifying biomarkers (molecules found in the body that show a specific disease or disease stage) or creating cell-targeted treatments for T1D. Supported by ORIP (K01OD028759), NCI, NIA, NIAID, NIDDK, and NIGMS.
Engineered Epithelial Curvature Controls Paneth Cell Localization in Intestinal Organoids
Yavitt et al., Cell Biomaterials . 2025.
https://pubmed.ncbi.nlm.nih.gov/40270579
Intestinal organoids, laboratory-grown mini-organs that model the intestine, are emerging as a new complementary approach to study disease progression, provide functional tissue for transplantation, and use in drug screening applications. Researchers have developed a new method to design the architecture of intestinal organoids by engineering the curvature of their tissue. Using a light-sensitive hydrogel, researchers precisely controlled the width and depth of intestinal organoids, mimicking the natural intestinal folds. This structure guided the placement of Paneth cells, which are key to gut health and immunity. By improving the consistency of cell organization, this approach enhances the reproducibility and functionality of organoid models, making them more useful for studying diseases, testing drugs, and advancing restorative medicine. Supported by ORIP (S10OD034320), NCI, NHLBI, and NIDDK.
Inferring Drug–Gene Relationships in Cancer Using Literature-Augmented Large Language Models
Lai et al., Cancer Research Communications. 2025.
https://pubmed.ncbi.nlm.nih.gov/40293950
Scientific literature contains a vast wealth of information on cancer and cancer-targeting drugs. Researchers developed GeneRxGPT, a large language model (LLM)–powered tool that analyzes biomedical literature to uncover drug–gene relationships for cancer treatment. By integrating PubMed data and advanced LLMs, this tool overcomes limitations of static LLMs (e.g., outdated knowledge, misleading results). GeneRxGPT was validated against curated databases and identified both established and emerging therapeutic cancer treatments. A case study in liver cancer showed a key link between a particular set of mutations and sensitivity to the cancer drug sorafenib, pointing to a new treatment strategy. Designed for accessibility, GeneRxGPT is a promising resource to accelerate cancer drug discovery that helps researchers without coding expertise explore drug–gene interactions. Supported by ORIP (S10OD028483, R03OD036494), NCI, NIBIB, NIDDK, and NIGMS.
Canine Distemper Virus Phylogenetic Structure and Ecological Correlates of Infection in Mesocarnivores Across Anthropogenic Land Use Gradients
Wilson et al., Microbiology Spectrum. 2025.
https://pubmed.ncbi.nlm.nih.gov/40029380
Humans’ use of land affects infectious diseases and how they interact with wildlife, domestic animals, and other humans by changing host spatial distribution, behavior, density, and population dynamics. This study examines how human-driven changes to the environment affect the spread of canine distemper virus (CDV) in mesocarnivores—mid-sized predators like raccoons, red foxes, and skunks. Researchers analyzed a database of CDV-infected animals (both sexes included) across the southeastern United States. They found that infection patterns were influenced by environmental factors, such as elevation, land use, precipitation, and age. CDV cases were more likely in areas with intense human activity and lower elevations. These findings can help identify high-risk zones for monitoring, improving early detection and helping prevent CDV from spreading between wildlife, domestic animals, and humans. Supported by ORIP (T35OD010433).