Selected Grantee Publications
- 608 results found
The Atypical Quorum Sensing System of Classical Brucella Species
Caudill and Caswell et al., Journal of Bacteriology. 2025.
https://pubmed.ncbi.nlm.nih.gov/41222302
Brucella species are a major public health concern because they trigger disease in both animals and humans and cause global economic losses. These bacteria have evolved to replicate in host cells—particularly macrophages (a type of immune cell). Brucella species have a specialized quorum sensing system (a way that bacteria communicate with each other using signaling molecules) that is essential for infecting the host and intracellular trafficking (the process of moving various components within the cell). This review describes the typical aspects of Brucella quorum sensing. Areas of limited knowledge that require additional research also are discussed. Supported by ORIP (T32OD028239) and NIAID.
Dominant Effects of the Immediate Environment on the Gut Microbiome of Mice Used in Biomedical Research
Ericsson et al., mSystems. 2025.
https://pubmed.ncbi.nlm.nih.gov/41222144
One potential concern when using mouse models is their reproducibility and predictive value for human disease. However, genetically engineered mouse (GEM) models are vital for studying gene function and the effects of environmental factors in biological systems. The microbiome (the collection of microbes found in the body) of GEM models significantly influences model phenotypes (physical characteristics) and thus represents a possible source of poor reproducibility. Researchers collected fecal samples from 275 unique GEM models at 84 different research institutions. These research institutions were located across 34 U.S. states and 7 other countries. Results showed that the laboratory environment was the main factor in shaping the microbiome, and beta-diversity similarities were observed. A surprisingly high prevalence and amount of Helicobacter species was observed in the GEM model microbiomes. This highlights the importance of collecting fecal samples in phenotyping studies to understand how the microbiome affects the results. Supported by ORIP (U42OD010918).
A Tandem Repeat Atlas for the Genome of Inbred Mouse Strains: A Genetic Variation Resource
Ren et al., iScience. 2025.
https://pubmed.ncbi.nlm.nih.gov/41142115
Tandem repeats (TRs) are repetitive DNA sequences. TRs are a significant source of genetic variation in the human population, responsible for unique biomedical traits among individuals and more than 60 genetic diseases. Researchers used long-read sequencing and state-of-the-art computational programs to produce a database of more than 2 million TRs that cover 39 inbred mouse strains (males used). Results showed that there were important similarities and differences among species and that TR alleles (alternative versions of a gene) are important for genetic discovery. Analysis of two biomedical phenotypes (physical characteristics), which were characterized in inbred mouse strains more than 40 years ago, identified the genetic factors that can cause these phenotypes. This research is essential for characterizing the unique genetic variations that cause trait differences and advancing fundamental biological research and translational medicine. Supported by ORIP (R24OD035408) and NIDCD.
Exceptional Diversity of Allorecognition Receptors in a Nonvertebrate Chordate Reveals Principles of Innate Allelic Discrimination
Rodriguez-Valbuena et al., PNAS. 2025.
https://pubmed.ncbi.nlm.nih.gov/41129228
Allorecognition—the ability to distinguish self from non-self—is found in many species and is the basis for many processes, such as mate choice, space competition, and immune function. Botryllus schlosseri is a marine invertebrate (a life form lacking a spine) that has many similarities to vertebrates in allorecognition genomic organization and signaling pathways. Researchers used B. schlosseri to investigate allorecognition and identified an unprecedented level of receptor diversity and adaptive ability in the alleles (alternative versions of a gene) used to determine compatibility. These results provide insight into signal processing and allorecognition processes across a broad range of animals. Supported by ORIP (R21OD030520) and NIGMS.
Conditional Dmd Ablation in Muscle and Brain Causes Profound Effects on Muscle Function and Neurobehavior
Karuppasamy et al., Communications Biology. 2025.
https://pubmed.ncbi.nlm.nih.gov/41331052
People with Duchenne muscular dystrophy (DMD) have skeletal and cardiopulmonary weakness caused by changes to the dystrophin protein, and up to one-third also are diagnosed on the autism spectrum. Researchers created an improved mouse model that allowed them to remove large gene isoforms (mRNA variations of the gene that may alter function) within the coding for dystrophin. The mouse Dmd gene has several isoforms that affect the skeletal muscle, heart, and brain. Researchers were able to define tissue-specific requirements of dystrophin in skeletal muscle during early and postnatal muscle growth and regeneration. They also observed some learning, cognitive, and social deficits in this 4- to-6-month-old male mouse model that are shared by other DMD mouse models. This increased understanding of how dystrophin loss affects people with DMD will help researchers develop gene therapies and treatment strategies. Supported by ORIP (U54OD030167), NIAMS, NICHD, NIDA, and NINDS.
Deep Learning Approaches for Classifying Children With and Without Autism Spectrum Disorder Using Inertial Measurement Unit Hand Tracking Data: Comparative Study
Mutersbaugh et al., JMIR Medical Informatics. 2025.
https://pubmed.ncbi.nlm.nih.gov/41428363
Studies show that 50% to 88% of children with autism spectrum disorder (ASD) have differences in movement control. Researchers used an inertial measurement unit (IMU), an electronic device that measures aspects of the body, to track arm movements in 41 children (both sexes) with and without an ASD diagnosis during a hand–eye coordination task. The IMU data were used in multiple deep learning models, and the best model was retrained and reevaluated, resulting in an accuracy of 91.87% and an F1-score (a performance metric for deep learning models) of 93.66%. The study showed that different physical movement patterns in children with ASD can be identified by analyzing hand–eye coordination skills and suggested that small-scale deep learning models have the potential to help diagnose ASD. Supported by ORIP (S10OD021534), NICHD, and NIGMS.
Vinculin Y822 Phosphorylation Regulates Adhesion Remodeling During Cardiomyocyte Maturation
Li et al., Journal of Cell Science. 2025.
https://pubmed.ncbi.nlm.nih.gov/41231303
Mechanical forces play a vital role in regulating cell function. Mechanosensitive proteins are molecules on and within the cell that are needed to sense mechanical stimuli. Defects in the ability to sense and convert mechanical stimuli into biochemical signals within a cell are involved in the development of such diseases as asthma, cancer, and cardiomyopathy. In the heart, cell–matrix and cell–cell adhesions adjust in response to increased cardiac demand and growth, which are mechanical stimuli of the heart. Vinculin (VCL) is a mechanosensitive protein found in the heart that links the protein actin to cell–matrix and cell–cell adhesions. Using heart cell culture and mouse models (both sexes used), researchers studied how VCL regulates changes in these interactions. Results showed that phosphorylation of the amino acid pY822 in VCL regulates these adhesion interactions in the heart. This highlights the importance of post-translational modifications of proteins in heart function. Supported by ORIP (R21OD037863), NHLBI, NIA, and NIGMS.
Assessing Gut Microbial Provisioning of Essential Amino Acids to Host in a Mouse Model with Reconstituted Gut Microbiomes
Ayayee et al., Communications Biology. 2025.
https://pubmed.ncbi.nlm.nih.gov/41254155
Gut microbes produce many metabolites which are substances made when the body processes food into energy and materials for cells. Metabolites include fatty acids and essential amino acids (EAAs), and they can affect the host’s health. EAAs are vital for making proteins and are involved in many cellular functions. A major challenge in microbiome research is showing the function of gut microbes in hosts, such as how microbe-derived EAAs affect the host. Using 3-week-old female germ-free mice and mice with a restored gut microbiome, researchers showed that gut microbes did not contribute to host EAA pools across the brain, kidney, liver, and muscle tissues. This study highlights the need for more research on the functional restoration of gut microbes and the importance of analytical techniques when trying to understand microbial nutrients. Supported by ORIP (K01OD030514), NCI, and NIGMS.
Identification of Antibodies to Chondrocyte and Synoviocyte Antigens in Equine Osteoarthritis
Linde et al., Journal of Orthopaedic Research. 2025.
https://pubmed.ncbi.nlm.nih.gov/41117710
Approximately 33 million people in the United States suffer from osteoarthritis (OA), and the rate has doubled in the past 30 years. The immune processes that drive OA development are not well understood. Past rheumatoid arthritis studies have shown that antibodies (proteins that bind to a specific molecule and help the immune system destroy it) will target molecules on living cells in a patient’s body. OA is common in horses, which makes them a relevant model for studying the condition. To understand whether antibodies target live cells in joints, causing OA to worsen, researchers used 2- to 18-year-old horses (both sexes used). Blood and synovial fluid samples contained antibodies that target live cells—chondrocytes and synoviocytes—in the joint, and antibody concentrations were correlated with OA severity. This research will help inform future studies on antibody production and therapies to target immune pathways in OA. Supported by ORIP (K01OD037846) and NCATS.
Dual Chitosan Hydrogel and Polylactic Acid Microparticle Delivery System Reduces Staphylococcal Osteomyelitis and Soft Tissue Infection
Tucker et al., NPJ Biofilms Microbiomes. 2025.
https://pubmed.ncbi.nlm.nih.gov/41266425
The bacteria Staphylococcus aureus is a common cause of the bone infection osteomyelitis (OM). Biofilms are a community of bacteria within a matrix that grows on surfaces and is hard to treat with antibiotics. This biofilm-forming bacterial infection is treated with long-term, high-dose antibiotics. However, this extended use of antibiotics can cause organ damage and promote antibiotic resistance (meaning the drug is no longer effective in treating the bacterial infection). Developing biomaterials (naturally derived or engineered substances for medical use in the body) for localized antibiotic delivery is key to avoiding these negative outcomes. Researchers used polylactic acid microparticles in antimicrobial chitosan hydrogel (CH PLA), both loaded with fosfomycin antibiotic, to combat S. aureus infection. Using 13-week-old female CD rats, researchers showed that CH PLA reduced S. aureus infection. Local treatment of OM using CH PLA decreased the bone defect area and the amounts of bacteria present in the bone and soft tissue. CH PLA is a promising biomaterial that may be an effective alternative to long-term antibiotic use to prevent S. aureus–mediated OM. Supported by ORIP (T35OD010432) and NIGMS.