Selected Grantee Publications
- 666 results found
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).
Mutant Prion Protein Enhances NMDA Receptor Activity, Activates PKC, and Triggers Rapid Excitotoxicity in Mice
Lin et al., The Journal of Clinical Investigation. 2025.
https://pubmed.ncbi.nlm.nih.gov/40185484
This study examined how a mutant form of a prion protein (PrPC) linked to Alzheimer’s disease can harm neurons, one type of brain cell. The team used genetically modified male and female mice and showed that changes in PrPC disrupt neuronal communication and lead to overactivation of Nmethyl-d-aspartate (NMDA) receptors in the brain, which are important for neuronal signaling. Mice experienced seizures and damage to neurons that are important for memory. The findings suggest that PrPC triggers toxic chain reactions in the brain and that these reactions play a key role in neurodegeneration. This discovery may ultimately help scientists better understand the mechanisms behind neurodegenerative diseases. Supported by ORIP (T32OD017863, S10OD023527) NCI, NHLBI, NIA, and NINDS.
Sperm Derived H2AK119ub1 is Required for Embryonic Development in Xenopus laevis
Francois-Campion et al., Nature Communications. 2025.
https://pubmed.ncbi.nlm.nih.gov/40188103
Previous research shows that exposure of males to various environmental factors can affect offspring by modifying the genetic material in sperm. Epigenetics—changes in gene expression that occur without altering the DNA sequence—plays an important role in how embryos develop. DNA is wrapped around groups of histones, a type of structural support protein that regulate DNA compaction and gene expression. DNA compaction can be regulated by modifications to histones—including the attachment of ubiquitin molecules. Researchers studied the role of a particular ubiquitin modification to histones, H2AK119ub1, in embryo development of Xenopus laevis (African clawed frog). The results showed that sperm-derived H2AK119ub1 instructs egg factor–mediated remodeling of the DNA contributed by the sperm and is required for embryonic development. Supported by ORIP (R24OD031956).
Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Mutation Reduces Endothelial TDP-43 and Causes Blood–Brain Barrier Defects
Cheemala et al., Science Advances. 2025.
https://pubmed.ncbi.nlm.nih.gov/40238886
Mutations in the TARDBP gene, which encodes nuclear protein TAR DNA-binding protein 43 (TDP-43), are linked to neurodegenerative diseases, such as familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). This study showed that TDP-43 is reduced in brain endothelial cells (ECs) of male and female mice with this mutation—leading to blood–brain barrier (BBB) disruption and causing inflammation, protein buildup, and cognitive issues—mimicking key features of neurodegeneration. These findings suggest that endothelial TDP-43 loss contributes directly to BBB breakdown and disease pathology in ALS-FTD. Supported by ORIP (U54OD020351), NCI, NHLBI, NIA, and NINDS.
Synaptic Dysregulation in a Mouse Model of GRIN2D Developmental and Epileptic Encephalopathy
Teoh et al., Brain. 2025.
https://pubmed.ncbi.nlm.nih.gov/40200555
Researchers studied a gain-of-function mutation, V667l, in the GRIN2D gene, which is linked to severe developmental delays and epilepsy in children. Using a mouse model carrying the V664I variant (both sexes used), findings showed that the mutation caused early-onset seizures, abnormal brain activity, and learning impairments. Functional analysis demonstrated increased synaptic activity, notably in inhibitory GABAergic interneurons, leading to heightened hippocampal excitability. These findings highlight how this mutation alters excitatory and inhibitory neuronal signaling in the brain, supporting precision genetic therapy as a promising treatment strategy for patients with mutations in the GRIN2D gene. Supported by ORIP (U54OD020351), NCI, NIA, NICHD, NIMH, and NINDS.