Selected Grantee Publications
- 697 results found
Environmental and Developmental Factors Shape Anti-AAV Immunity in Pigs
Iroanya et al., Gene Therapy. 2026.
https://pubmed.ncbi.nlm.nih.gov/42215798
Adeno-associated viruses (AAVs) show promise for delivering gene therapies to treat monogenic (caused by changes in a single gene) diseases. Researchers evaluated the utility of pigs (sex not stated) as models for testing AAV-based therapies. Consistent with previous studies, they showed that pigs naturally produce antibodies (protective proteins made by the immune system) that can block AAV vectors. These antibodies appeared by 2 weeks of age and increased over time. Immune responses also varied by environment, with pigs in standard housing showing stronger and more diverse responses than those in highly controlled settings. Removing IgG (a type of antibody found in blood and extracellular fluid) restored AAV activity in laboratory tests. This study suggests that pigs can help researchers test ways to overcome immune barriers associated with gene therapies. Supported by ORIP (U42OD027090, U42OD035738).
Genome-Wide Association Mapping and Targeted Loss of Function Studies Identify Shroom3 as a Driver of Hyperpolyploidy and Ventricular Dilation
Purdy et al., PNAS. 2026.
https://pubmed.ncbi.nlm.nih.gov/42189988
Cardiomyocyte polyploidy (a condition where heart muscle cells replicate their DNA but fail to divide) is associated with responses to cardiac injury, but researchers do not fully understand the mechanisms explaining this effect. Researchers studied heart muscle cells in rats (both sexes used) and found that cells with extra chromosome copies were linked to weaker heart pumping and enlarged heart chambers. By scanning rat genomes, they identified the gene Shroom3 as an important driver of this process. When Shroom3 was disrupted in heart cells, polyploidy increased and heart function worsened. The findings suggest Shroom3 helps control heart cell structure and may offer clues for understanding heart disease. Supported by ORIP (R24OD024617), NHLBI, and NIGMS.
Development of a Spatially Defined 3D In Vitro Coculture Construct Modeling Pancreatic Cancer–Associated Cachexia
Kuss et al., Biofabrication. 2026.
https://pubmed.ncbi.nlm.nih.gov/41985529
Up to 85% of pancreatic cancer patients experience cachexia, a debilitating metabolic wasting syndrome. Researchers developed a 3D organoid platform that mimics in vivo interfaces, allowing them to better understand the interactions between cancer cells and adipocytes (fat cells). The system precisely compartmentalizes adipocytes and cancer cells within a hydrogel while reproducing key processes seen in the body, including fat breakdown, changes in fat cells that increase energy use, and the spread of pancreatic cancer cells into surrounding fatty tissue. The model provides a controlled, physiologically relevant environment for understanding the mechanisms of cancer-associated cachexia and for testing potential treatments. Supported by ORIP (S10OD030486), NCI, and NIGMS.
Construction of Saturated Tn-Seq Libraries of Brucella abortus S19 for Transposon Insertion and Effective Density Analysis Across Stress Conditions
Knebel et al., Microbiology Resource Announcements. 2026.
https://pubmed.ncbi.nlm.nih.gov/41984032
Brucella abortus is a bacterial pathogen that can spread between animals and humans. It is highly resilient and can survive in harsh conditions, including acidic environments, exposure to harmful oxygen-containing molecules, and the body’s natural antimicrobial defenses. To better understand how B. abortus survives and causes infection, researchers created large sequencing libraries using the weakened S19 strain of the bacteria with different genetic disruptions. Using this tool, they identified genes that are important for the pathogen’s survival. This rich dataset can be used to explore the genetic fitness of the pathogen B. abortus across multiple environments. Supported by ORIP (T32OD011126).
Impact of Sample Processing Method and Volume on 16 S rRNA Profiling of the Urobiome
Ramirez et al., BMC Microbiology. 2026.
https://pubmed.ncbi.nlm.nih.gov/42251288
The urinary microbiome (urobiome) plays an important role in the health of the urinary and reproductive systems in both humans and animals. Studying these microbial communities can be challenging because urine contains very small numbers of microbes. Researchers compared two methods for processing urine samples from dogs of both sexes—vacuum filtration and pelleting—as well as different sample volumes. They evaluated how these approaches affected bacterial DNA recovery, contamination levels, and the diversity of microbes detected. The results showed that both methods produced similar microbial profiles, even when using smaller urine samples. Overall, the findings suggest that differences in urinary microbiomes are driven mainly by biology rather than sample-processing methods, provided that careful steps are taken to control contamination. Supported by ORIP (T35OD011118), NCATS, and NIEHS.
Triphenyl Phosphate Promotes Lipid Accumulation in Human Mesenchymal Stem Cells Through Metabolic Stress Pathways
Gronske et al., Archives of Toxicology. 2026.
https://pubmed.ncbi.nlm.nih.gov/42228132
Organophosphate esters (OPEs) are chemicals commonly added to plastics and other products to improve flexibility and reduce fire risk. Growing evidence suggests that OPEs can interfere with normal cell functions and place stress on cells, potentially affecting metabolism and other important biological processes. In this in vitro laboratory study, researchers analyzed the effects of an OPE—triphenyl phosphate (TPhP)—on the development and function of human mesenchymal stem cells (which can develop into bone, cartilage, and fat cells). They found that TPhP may disrupt the balance between bone formation and fat metabolism, potentially promoting fat accumulation within bone-forming tissues. Ultimately, TPhP may affect the biological pathways involved in various health conditions, including obesity, type 2 diabetes, and osteoporosis. Supported by ORIP (T35OD011070) and NIEHS.
Impact of Tongue Exercise on Hypoglossal Axis Survival, Structure, and Output in a Rodent Model of Hypoglossal Motor Neuron Degeneration
Keilholz et al., Journal of Neurophysiology. 2026.
https://pubmed.ncbi.nlm.nih.gov/42012472
Motor neuron diseases (MNDs) are a group of neuromuscular (communication between nerves and muscles) disorders caused by the progressive loss of motor neurons. Motor neurons are nerve cells that control such important activities as breathing and swallowing. Obstructive sleep apnea (OSA) is common in patients with MNDs, and OSA may aid the progression of MNDs. Using a 3- to 4-month-old male rat model for MND—and CTB-SAP injections to mimic motor neuron loss in OSA—researchers studied whether high-repetition, low-resistance tongue exercises protected against motor neuron degeneration. Results showed that the tongue exercises increased microglia (an immune cell of the nervous system) density and reduced deficits in nerve outputs. These findings highlight the potential use of tongue exercises to improve functional outcomes in patients with OSA and MND. Supported by ORIP (T32OD011126) and NHLBI.
ABL Kinases Regulate FGF Signaling Independent of CRK Phosphorylation to Prevent Peters Anomaly Type II
Wu et al., Nature Communications. 2026.
https://pubmed.ncbi.nlm.nih.gov/42129167
Peters anomaly is a developmental disorder of the front of the eye. It is one of the most common causes of babies being born with vision issues, including a cloudy cornea (the transparent lens that covers and protects the eye). Using male and female mouse models for Peters anomaly, researchers found that removing molecules known as ABL kinases can restore lens formation when FGF cell signaling is missing. However, results also showed that deleting ABL kinases causes Peters anomaly type II through a pathway that does not rely on ERK signaling. This defect was corrected when target molecules—CRK and CRKL—were reduced. This study found a signaling pathway, ABL-PTPN12-p130CAS, that controls the mechanical forces needed for the lens vesicle to separate properly during eye development. These findings highlight a new signaling pathway that could be targeted in treatment strategies for Peters anomaly type II. Supported by ORIP (R21OD037863) and NEI.
Immune–Microbiome Coordination Defines Interferon Setpoints in Healthy Humans
Babdor et al., Cell. 2026.
https://pubmed.ncbi.nlm.nih.gov/41806833
The gut microbiome (the collection of different microbes) plays an important role in shaping the immune system, but the relationship between the gut microbiome and baseline immune states in healthy people remains poorly understood. In this study, researchers collected blood and stool samples from 110 male and female patients from the San Francisco Bay area. The researchers completed multiomics analyses of the samples to identify coordinated immune and microbial patterns. Results showed that interferon response was one of the most variable immune features found in blood samples. This feature was closely linked to changes in microbiome makeup, microbial pathways, and metabolic products in stool samples. These immune and microbiome features also were shown to remain stable. These findings highlight a strong relationship in healthy people between baseline immune states and the microbiome. Data from this study could help identify immune–microbiome features that underlie disease susceptibility and therapeutic response. Supported by ORIP (S10OD018040, S10OD028511), NCI, NIDCR, NIDDK, NHLBI, and NIGMS.
Co-localization of Lymph Node Therapeutics Enhances T Cell Activation and Anti-tumor Response
Shen et al., Biomaterials. 2026.
https://pubmed.ncbi.nlm.nih.gov/41172599
Lymph nodes (LNs) play an important role in creating and altering immune responses. Researchers were interested in learning how the organization of antigens (markers seen as foreign and recognized by the immune system) and adjuvants (agents that cause a stronger immune response) within LNs influence anti-tumor immune responses. In this study, antigens and adjuvants were loaded as cargo into microparticles. Using cell cultures and 6- to 10-week-old female mice, researchers showed that localizing cargo-loaded microparticles to the same LN created a strong antigen-specific T-cell response and provided antitumor protection. Results also showed that separating microparticles across different LNs decreased immune efficacy. Mixed-cargo microparticles caused similar immune responses compared with multiple, single-cargo microparticles if injections were localized to the same LN. These findings support the translation of mixed-cargo degradable microparticles for LN-targeted immunotherapy (treatments that modify the immune system to fight cancer) strategies. Supported by ORIP (S10OD025223), NCI, and NIAID.