Selected Grantee Publications
- 635 results found
A Porcine Model of Fanconi Anemia
Hergert et al., PLoS One. 2025.
https://pubmed.ncbi.nlm.nih.gov/41171815
Fanconi anemia (FA) is an autosomal recessive disorder (a mutated gene must be passed down from both parents for symptoms to develop). It causes birth and developmental defects because of disrupted DNA repair. Without the ability to repair DNA damage, mutations continue to collect in the patient’s tissues, which leads to anemia, bone marrow failure, and cancer. Murine (mouse and rat) models for FA do not mimic the key clinical symptoms of FA, such as anemia. A pig model of FA could accurately mimic many of the clinical features seen in human patients because pigs have similar physiology and a relatively long lifespan. Researchers targeted the FANCA gene in domestic pigs. The FANCA porcine model (sex not stated) showed skeletal abnormalities, extreme sensitivity to agents that cause DNA crosslinks (a type of DNA damage), hematopoietic progenitor cell reduction, enlarged red blood cells, and reduced neutrophil (a type of immune cell) numbers in peripheral blood. Mitomycin C treatment resulted in a tenfold increase in chromosomal radials—where a segment of one chromosome breaks off and attaches to another, causing unbalanced rearrangements due to improper DNA repair—which is a diagnostic marker for FA in patients. This study shows that the FANCA porcine model is a promising preclinical model for developing strategies to prevent bone marrow failure and malignancies in FA patients. Supported by ORIP (U42OD011140) and NHLBI.
A Thymus-Independent Artificial Organoid System Supports Complete Thymopoiesis from Rhesus Macaque-Derived Hematopoietic Stem and Progenitor Cells
Wilde et al., Biomedicines. 2025.
https://pubmed.ncbi.nlm.nih.gov/41301785
The creation of T cells within the body involves many steps that begin with T cell progenitor cells (cells that become T cells) in the bone marrow. T cells finish developing and multiply in the thymus. Although nonhuman primates (NHPs) serve as key models for studying T cell development and output under normal and disease conditions, no non-animal technology for T cell development and output currently exists. To address this gap, researchers developed an NHP-specific organoid (3D cell cultures that contain several cell types and mimic specific functions of an organ). This NHP organoid mimics thymopoiesis (a series of events leading to the creation of T cells) in a thymus-tissue-free environment. This study is the first to demonstrate an NHP-specific artificial thymic organoid that models thymopoiesis and can be used in future research studies to understand T cell development and output in different diseases. Supported by ORIP (R21OD035572, P51OD011132) and NIAID.
Cooked Broccoli Alters Cecal Microbiota and Impacts Microbial Metabolism of Glucoraphanin in Lean and Obese Mice
Zhao et al., Molecular Nutrition & Food Research. 2025.
https://pubmed.ncbi.nlm.nih.gov/39962804
Brassica vegetables, such as broccoli, are a unique source of compounds known as glucosinolates (GSLs). The protein myrosinase turns GSLs into isothiocyanates (ITCs). ITCs are bioactive compounds that display many health benefits and reduce the risk of certain cancers, degenerative diseases, cardiovascular disease, and inflammation. Cooking broccoli deactivates the myrosinase found in the vegetable, so our body relies on bacteria-derived myrosinase to convert GSLs into ITCs. The gut microbiome differs between lean and obese populations, and differences in the gut microbiome can hinder the conversion of GSLs to ITCs. The researchers studied the impact of cooked broccoli on cecal (a part of the large intestine) microbial conversion of glucoraphanin (GRP), the most abundant GSL of broccoli, in 16-week-old lean and obese male mice. The findings suggest that eating cooked broccoli enhances microbial GRP conversion and produces more bioactive ITCs. Eating cooked broccoli also changed the cecal microbiome composition and increased the abundance of several types of bacteria. This study can inform future strategies that focus on changing microbial pathways that break down GSLs to promote health in different populations of people. Supported by ORIP (T35OD011145).
Inhalable Hsa-miR-30a-3p Liposomes Attenuate Pulmonary Fibrosis
Liu et al., Advanced Science. 2025.
https://pubmed.ncbi.nlm.nih.gov/40119620
The extracellular matrix is a substance that surrounds the cells to provide structural support and enhance signaling. Idiopathic pulmonary fibrosis (IPF) is an incurable type of lung disease in which too much extracellular matrix is deposited in the lungs. Current treatments for IPF only manage symptoms or slow disease progression. Liposomes, which are fat-like particles that can be created to contain drugs or other substances, may serve as a therapy for IPF. Inhalable hsa-miR-30a-3p-loaded liposomes (miR-30a) were studied as potential treatments for pulmonary fibrosis in 6-week-old male mice. Previous studies have found that exosomes (cellular packages that allow molecules to be passed from one cell to another) with therapeutic effects on pulmonary fibrosis are enriched in these liposomes. The researchers showed that inhaled miR-30a reduced some effects of IPF and improved lung function. Supported by ORIP (T35OD011070), NCATS, and NHLBI.
The RSPO2 Gene Is Associated with Bilateral Anterior Amelia in Chihuahuas
Chevallier et al., Mammalian Genome. 2025.
https://pubmed.ncbi.nlm.nih.gov/40131457
Bilateral anterior amelia (BAA), the absence at birth of bones beyond the shoulder blade, can occur in chihuahuas when both parents have a mutated copy of the RSPO2 gene. Researchers used a genome-wide association study to compare DNA markers in affected chihuahuas with those in normal chihuahuas, as well as homozygosity mapping to find identical versions of a gene passed down from both parents. Results from nine chihuahuas with BAA (sex not stated) identified a region on chromosome 13 that contains the RSPO2 gene, which has been linked to limb absence in cattle and humans. This finding will improve genetic testing in chihuahuas to reduce the occurrence of BAA and increase understanding of the RSPO2 gene. Supported by ORIP (T35OD010956).
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.