Selected Grantee Publications
- 644 results found
Caspase-11 Drives Macrophage Hyperinflammation in Models of Polg-Related Mitochondrial Disease
VanPortfliet et al., Nature Communications. 2025.
https://pmc.ncbi.nlm.nih.gov/articles/PMC12092707
Mitochondria are the energy-producing organelles within cells. Mitochondrial diseases develop from dysfunction of this organelle. These diseases lead to chronic health impairments, which can be worsened by environmental exposures—including bacterial infections. Researchers used a 7- to 12-month-old mouse model (sex not specified) to study polymerase gamma (Polg)–related mitochondrial disease. They found that infection with the bacteria Pseudomonas aeruginosa causes macrophages (a type of immune cell) to have an increased response. The response happens through cytokine-mediated increases of caspase-11 and guanylate-binding proteins, which leads to lung inflammation. These findings will help scientists find targets to develop therapies to limit infection- and inflammation-related complications in mitochondrial diseases. Supported by ORIP (U54OD030187) and NHLBI.
Generation of Inositol Polyphosphates Through a Phospholipase C-Independent Pathway Involving Carbohydrate and Sphingolipid Metabolism in Trypanosoma cruzi
Bertolini et al., mBio. 2025.
https://pubmed.ncbi.nlm.nih.gov/40172212
Millions of people are infected with the parasite Trypanosoma cruzi. T. cruzi causes Chagas disease, an infectious disease that causes damage to cardiovascular, nervous, and digestive systems. T. cruzi relies on inositol pyrophosphates (important signaling molecules) for survival. Researchers identified an alternative phospholipase C-independent pathway for producing these molecules (e.g., glucose 6-phosphate, inositol phosphoceramide). Disrupting this pathway impaired parasites’ ability to make inositol pyrophosphates. This discovery reveals a promising drug target for treating Chagas disease. Supported by ORIP (T35OD010433) and NIAID.
Detection of Live Attenuated Measles Virus in the Respiratory Tract Following Subcutaneous Measles-Mumps-Rubella Vaccination
Watkins et al., The Journal of Infectious Diseases. 2025.
https://pubmed.ncbi.nlm.nih.gov/39504437
The live attenuated measles vaccine (LAMV) is very effective in preventing measles. LAMV produces mucosal immunity in the respiratory tract, but the mechanism remains unknown. Researchers found that LAMV could be detected in the respiratory tract of children and macaques for up to 3 weeks after receiving the measles-mumps-rubella (MMR) vaccine. Scientists isolated LAMV from macaques’ lungs (sex not specified) and found that local viral activity in the respiratory tract could potentially help stimulate mucosal immunity without viral transmission. These findings highlight the importance of mucosal immune responses and provide insights as to how the MMR vaccine could protect against measles. Supported by ORIP (T32OD011089) and NIAID.
Sphingosine–1–phosphate Signaling Mediates Shedding of Measles Virus–Infected Respiratory Epithelial Cells
Brockhurst et al., Journal of Virology. 2025.
https://pubmed.ncbi.nlm.nih.gov/40145737
Measles virus (MeV) is an infectious respiratory virus that has a significant global impact and is a major cause of childhood mortality. In 2022, MeV infection caused more than 136,000 deaths. A single infected person can transmit MeV to nearly 20 other people. Respiratory epithelial cells (cells that line the respiratory system) are the target of MeV infection, and shedding these cells into airborne droplets causes transmission to other people. Researchers used epithelial cells isolated from the tracheas of rhesus macaques (sex not specified) to understand the mechanisms underlying how MeV-infected epithelial cells are shed. Results showed that sphingosine-1-phosphate (S1P) signaling plays a key role in cell shedding. Inhibiting S1P signaling delayed MeV-infected epithelial shedding and increased the amount of virus in the epithelial lining. These findings demonstrate the key role of host cellular responses in MeV infection. Supported by ORIP (T35OD024982, T32OD011089) and NIAID.
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.