Selected Grantee Publications
- 628 results found
Longitudinal In Vivo 3T MRI of Naturally Occurring Early Osteochondrosis Lesions in the Piglet Humeral Epiphyseal Cartilage and Growth Plate
Armstrong et al., Journal of Orthopaedic Research. 2025.
https://pubmed.ncbi.nlm.nih.gov/40783804
Osteochondrosis/osteochondritis dissecans (OC/OCD) is a developmental orthopedic disease primarily affecting the knee, ankle, and elbow joints of children and multiple animal species. Subclinical (a disease that is not yet severe enough to show definite symptoms) lesions of OC/OCD have been collected and studied under a microscope after death. To be able to monitor the progression of OC/OCD lesions and determine which lesions require surgical intervention in vivo (within a living organism), a magnetic resonance imaging (MRI) technique that allows precise data capture is needed. Researchers used 4-week-old female pigs to determine the use of noninvasive 3T MRI to identify OC lesions in the elbow joint and growth plate of the humerus (the long bone of the upper arm). The results show that in vivo 3T MRI may allow long-term monitoring of early OC lesions to determine whether a lesion is resolving or progressing to clinical OCD that may require surgery. Supported by ORIP (K01OD034070, K01OD021293), NIAMS, and NIBIB.
Remdesivir Postexposure Prophylaxis Limits Measles-Induced “Immune Amnesia” and Measles Antibody Responses in Macaques
Chan et al., JCI Insight. 2025.
https://pubmed.ncbi.nlm.nih.gov/40306326
Measles is a highly contagious viral disease that is a leading cause of childhood illness and death around the world. The measles virus (MeV) replicates considerably in tissue where immune cells are produced and activated. MeV causes the immune system to lose circulating antibodies (a protein that binds to a specific antigen and helps the immune system destroy it) against other pathogens, which leaves the infected child susceptible to other infectious diseases. Researchers wanted to determine whether remdesivir, a broad-spectrum antiviral (a drug that affects a wide range of viruses), can hinder MeV-induced loss of antibodies to other pathogens. They measured antibody reactivity using a MeV rhesus macaque model (both sexes used). Remdesivir given 3–14 days after MeV infection limited the loss of antibodies to non-MeV pathogens. Remdesivir also reduced the immune system’s ability to mount an antibody response to MeV. This study shows that early treatment of measles with remdesivir prevents the loss of antibodies against other pathogens but lessens the response to MeV. Supported by ORIP (T32OD011089) and NIAID.
Embryonic Exposure to TPhP Elicits Osteotoxicity via Metabolic Disruption in Oryzias latipes
Gronske et al., Toxics. 2025.
https://pubmed.ncbi.nlm.nih.gov/40863930
Triphenyl phosphate (TPhP) is a widely used compound that makes materials more flexible and also acts as a flame retardant. This study examined the effects of embryonic TPhP exposure on Oryzia latipes, a fish model that is relevant to human bone biology. O. latipes embryos were exposed to TPhP and studied through early larval stages. The results show that TPhP disrupts bone formation, delays bone regeneration, and alters gene pathways involved in bone and cartilage diseases. The study highlights the value of small fish models for studying toxins from the environment and the risks to bone health. Supported by ORIP (T35OD011070) and NIEHS.
PLAA/UFD-3 Regulates P-bodies Through Its Intrinsic Disordered Domain
Das et al., PNAS. 2025.
https://pubmed.ncbi.nlm.nih.gov/40560612
Maintaining protein balance in cells is essential for survival and adapting to new environments in all species. In eukaryotes (organisms that have a membrane-bound nucleus, from yeast to humans), this balance is controlled through different stages, such as making proteins, modifying them, and breaking them down. The phospholipase A2 activating protein (PLAA) is a protein found in all eukaryotes that helps sort and degrade proteins through interactions with other molecules. However, its exact targets and interactions are not well understood. Researchers studied PLAA in nematode worms and discovered it has a unique role in cellular processing bodies, called P-bodies, that process cytoplasmic mRNA (molecules that carry the genetic information to make proteins). PLAA interacts with another protein, DCAP-1, which helps process mRNA. This study suggests that PLAA forms a complex with DCAP-1 to regulate protein balance in two ways: breaking down proteins and managing mRNA in P-bodies. Supported by ORIP (R24OD023041, P40OD010440) and NHGRI.
Phage-Displayed Synthetic Library and Screening Platform for Nanobody Discovery
Xia et al., eLife. 2025.
https://pubmed.ncbi.nlm.nih.gov/40748049
Nanobodies are tiny, stable antibodies (a protein that binds to a specific antigen and helps the immune system destroy it) from camels that are valuable in research and medicine. Traditionally, creating nanobodies requires immunizing camels, which is expensive and time consuming. In this study, researchers described the development of a high-throughput screening method for nanobodies using a synthetic library displayed on phages (viruses that infect bacteria). They tested this method by screening for nanobodies that target various secreted proteins found in fruit flies. The identified nanobodies worked well for applications like immunostaining (labeling a specific protein in a sample on a microscope slide) and immunoblotting (a technique that measures the amount of protein in a sample using an antibody). The synthetic library used in this study is now available for nonprofit use, facilitating the development of high-quality nanobodies for biomedical research and therapeutic development. Supported by ORIP (R24OD035556) and NIGMS.
Polyploidy Promotes Transformation of Epithelial Cells into Nonprofessional Phagocytes
Huang et al., PNAS. 2025.
https://pubmed.ncbi.nlm.nih.gov/40694325
Removing dead and damaged cells is important for keeping organisms healthy. Under stressful conditions, such as food scarcity, infection, or temperature changes, unnecessary cells can be removed to save energy and maintain balance. Phagocytes are immune cells that remove invading microbes, foreign material, and damaged or dead cells. Specific cells like macrophages act as phagocytes, but other cells, called nonprofessional phagocytes (NPPs), also can take on this role if needed. NPPs need to change from an immature to mature state and undergo activation before they can clear dead and damaged cells. However, the molecular and cell pathways that cause the transitions and activation of NPPs are not well understood. Researchers used fruit flies to study the transition and activation of NPPs. They found that in fruit flies, certain cells in the ovaries can become NPPs capable of removing dead cells during egg development, which is triggered by a signaling pathway called Notch. This process involves the cells multiplying their chromosome sets to more than two, a cell state called polyploidy. Then, the polyploid cells activate JNK signaling, which helps them engulf and remove the dead cells. This research suggests the importance of polyploidy for NPPs to function properly and maintain health during stress. Supported by ORIP (R24OD031953), NCI, NIGMS, and NINDS.
Functional Analysis of Pathogenic Variants in LAMB1-Related Leukoencephalopathy Reveals Genotype–Phenotype Correlations and Suggests Its Role in Glial Cells
Yasuda et al., Human Molecular Genetics. 2025.
https://pubmed.ncbi.nlm.nih.gov/40237576
Cells are surrounded by a matrix, known as the basement membrane, that provides structural support and enhances signaling. Laminin B1 (LAMB1) is a matrix protein in the basement membrane that helps form this supportive structure around cells. Mutations (mistakes in the DNA sequence) in the LAMB1 gene can cause rare neurological disorders. Researchers studied the fruit fly version of the LAMB1 gene, which is LanB1. Using fruit flies, the researchers were able to gain insight into the link between LAMB1 gene mutations and disease symptoms. The LanB1 protein is found in a subset of brain cells, called glia cells, and in the blood–brain barrier. Reducing the amount of LanB1 protein in the blood–brain barrier caused shorter lifespans and movement defects in the fruit flies. Human LAMB1 was not functional in flies, but fly experiments showed that some LanB1 mutations cause severe defects, while others were milder. Tests in human cells suggested some LAMB1 mutations might cause disorders, even in the presence of a normal copy of LAMB1. This study reveals the role of LanB1 in keeping the healthy structure of the fly blood–brain barrier and understanding the consequences of different LAMB1 mutations in humans. Supported by ORIP (R24OD022005, R24OD031447).
Distinguishing PEX2 and PEX16 Gene Variant Severity for Mild, Severe and Atypical Peroxisome Biogenesis Disorders
Gomez et al., Disease Models and Mechanisms. 2025.
https://pubmed.ncbi.nlm.nih.gov/40621817
Peroxisomes are structures in cells that play an important role in metabolism and chemical changes of complex fats. Peroxisomal biogenesis disorders (PBDs) are caused by mutations in peroxin (PEX) genes. PBDs are autosomal recessive diseases—a mutated PEX gene must be passed down from both parents. In patients, symptoms of PBD range from mild to severe multi-organ system defects depending on gene mutations and even different mutations in the same gene. Researchers wanted to understand how different mutations cause the variation in symptoms seen in patients. In fruit flies, the researchers replaced the fly Pex genes with two human PEX genes—PEX2 and PEX16—and different mutant forms of these genes. Researchers found that some mutations caused severe symptoms, such as seizure-like behavior, while others were milder. Introducing a normal functional copy of the human PEX genes into the flies with mutant Pex genes alleviated the symptoms. Further studies with fruit flies will help us understand how different PEX gene mutations affect PBD severity in patients. Supported by ORIP (R24OD031447), NICHD, and NINDS.
miR-33 Inhibition as a Novel Therapeutic Approach for Treating Muscular Dystrophy
Lopez and Alexander, EMBO Molecular Medicine. 2025.
https://pubmed.ncbi.nlm.nih.gov/40695995
Duchenne muscular dystrophy (DMD) is a devastating disorder caused by changes in the dystrophin gene sequence, which results in the absence of a functional dystrophin protein. Several microRNAs (a type of RNA that can bind to other molecules) can alter DMD disease by changing gene expression. In this review article, the authors discuss inhibiting microRNAs as a new therapy for DMD. Researchers have shown in a DMD mouse model that blocking miR-33a/b, a microRNA, can improve muscle regeneration (regrowth of damaged tissue) and reduce DMD symptoms. Anti-microRNA oligonucleotides (AMOs) are short chains of DNA or RNA that block microRNAs. Injection of an AMO that blocks miR-33a/b in the DMD mouse model improved muscle regrowth and increased gene pathways involved in muscle regrowth. These studies highlight the impact of microRNA signaling pathways in DMD and show how they could serve as targets for new therapies to treat the disease. Supported by ORIP (U54OD030167) and NINDS.
Genomics and Histopathology in Interstitial Cystitis/Bladder Pain Syndrome
Ruetten et al., Neurourology and Urodynamics. 2025.
https://pubmed.ncbi.nlm.nih.gov/40671333
In April 2025, researchers held a meeting to come to a global agreement on the diagnostic criteria, visible features, and possible causes of interstitial cystitis/bladder pain syndrome (IC/BPS) and to review treatment outcomes. A patient can be diagnosed with IC/BPS when they experience pelvic and bladder pain with other urinary tract symptoms, such as urinary frequency and urgency. This subreport defines the distinct differences between Hunner lesion disease (HLD) and non-Hunner lesion disease (non-HLD) in IC/BPS. HLD is an inflammatory disease of the bladder, and non-HLD is a widespread nervous system disorder in which symptoms are not limited to the bladder. This concept of distinct differences between HLD and non-HLD could be useful in identifying physical characteristics of and diagnosing IC/BPS and developing biomarkers (molecules that show a disease is present) for the condition. Supported by ORIP (T32OD010957) and NIDDK.