Selected Grantee Publications
- 644 results found
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.
Metabolomic Profiling and Characterization of a Novel 3D Culture System for Studying Chondrocyte Mechanotransduction
Brahmachary et al., Cellular and Molecular Bioengineering. 2025.
https://pubmed.ncbi.nlm.nih.gov/41328310
Osteoarthritis (OA) is a chronic degenerative joint disease that affects more than 37% of people over age 60. The pericellular matrix (PCM), the microenvironment that directly surrounds each cartilage cell, plays an important role in mechanotransduction. This process allows cells to sense changes in outside physical forces and convert them into electrical signals and cartilage functions. Using a novel 3D culture system equipped with cyclical compression and loading stimulation to mimic physiological conditions, researchers studied human and bovine cartilage cell mechanotransduction under different cell culture conditions. Metabolomic profiling—a way of observing all chemical changes within a cell that produces compounds and energy for biological processes—showed unique changes and strong PCM development as indicated by the production of both collagens VI and II, suggesting the 3D culture system replicates the native PCM and physiological stiffness of cartilage. By providing a physiologically relevant 3D model, future studies can look into OA pathways, cartilage tissue engineering, and novel therapies. Supported by ORIP (S10OD028650), NIAMS, and NIGMS.
Cryo-EM Structures of HBV Capsids from Human Cells at Near-Atomic Resolution
Bianchini et al., Structure. 2025.
https://pubmed.ncbi.nlm.nih.gov/41314213
More than 800,000 deaths per year are caused by hepatitis B virus (HBV)–induced liver inflammation, cirrhosis (scarring liver), and hepatocellular carcinoma. Cryogenic electron microscopy (Cryo-EM) is a microscope technique that images samples cooled to very low temperatures. Using cryo-EM, researchers determined the structure of HBV capsids (a protein shell that surrounds and protects the virus) purified from human cells. Along with computer simulations and analyses, results highlighted the dynamic regulation of HBV capsid structure and how it contributes to virion (an infectious form of virus) secretion, viral assembly, and envelopment. This could be a potential mechanism for developing HBV-specific antiviral drugs for disease treatment. Supported by ORIP (S10OD028725), NIAID, and NIGMS.
Macrophage-Engaging IgG4 Antibody Triggers Cytotoxicity Against Integrin αvβ3+ Cancers
Reddy et al., Molecular Cancer Therapeutics. 2025.
https://pubmed.ncbi.nlm.nih.gov/41081633
Integrins are cell receptors that span the cell membrane and play an important role in signaling pathways—including survival and movement. Integrin αvβ3 is absent in most normal cells and is a biomarker of cancers that form in the epithelial tissue, lining most organs and body surfaces. Integrin αvβ3 also is a driver of tumor stemness (properties of cancer cells that promote tumor development) and drug resistance in epithelial cancers, which makes it an ideal target for therapy. Tumor-associated macrophages (TAMs) are immune cells that are abundant in the epithelial cancer microenvironment, but they reduce the efficacy of an antibody therapy that targets cells with integrin αvβ3. Using in vitro (outside of the body) cultures and 8- to 10-week-old female mice, researchers revealed an antibody-mediated therapy that activates the anti-tumor activities of TAMs to overcome drug-resistant, integrin αvβ3-positive epithelial cancer. This study supports the use of antibody-based therapies to activate immune cells and destroy the tumor. Supported by ORIP (K01OD030513), NCI, NIDDK, and NINDS.
Cross-species Protection Suggests Entamoeba histolytica Trogocytosis Enables Complement Resistance Through the Transfer of Negative Regulators of Complement Activation
Ruyechan et al., Infection and Immunity. 2025.
https://pubmed.ncbi.nlm.nih.gov/40741974
Amoebae are single-cell organisms that can be parasites to the human body. Entamoeba histolytica, a type of amoeba, causes diarrheal disease when it invades the intestine. E. histolytica spreads through the body using the bloodstream and can evade the immune system. Amoebae eat parts of human cells—an event known as trogocytosis—which allows them to display human proteins and resist being broken down by serum in the blood. Researchers wanted to identify how amoebae resist being broken down. Results showed that amoebae display host proteins that suppress the complement pathway of the immune system, which protects them from being broken down. Other microbes can perform trogocytosis of human cells, so understanding this method of resistance could be relevant to other infections. Supported by ORIP (T32OD011147) and NIAID.
Alternating Hemiplegia of Childhood Associated Mutations in Atp1a3 Reveal Diverse Neurological Alterations in Mice
Terrey et al., Neurobiology of Disease. 2025.
https://pubmed.ncbi.nlm.nih.gov/40381892
Pathogenic variants (changes in a gene that increase a person’s risk of developing a genetic disorder) in the Na+/K+ ATPase transmembrane ion transporter (ATP1A3) gene cause a spectrum of neurological disorders, including alternating hemiplegia of childhood (AHC). In patients, about 65% of AHC cases are caused by one of two specific mutations. Mouse models that mimic these mutations are limited by early death, which hinders our understanding of the molecular and cellular mechanisms that drive AHC. The researchers used a hybrid approach to create mouse models for these two most common ATP1A3 variations that did not suffer from early death. The researchers characterized the mouse models (both sexes used) and found that the two ATP1A3 variations cause different disease symptoms, including motor function impacts, behavior changes, and the inflammation of nervous system tissue. These mouse models can be used to test possible therapies for AHC. Supported by ORIP (U54OD030187, U42OD010921).
Neurocellular Stress Response to Mojave Type A Rattlesnake Venom: Study of Molecular Mechanisms Using Human iPSC-Derived Neural Stem Cell Model
Kumar et al., Biomolecules. 2025.
https://pubmed.ncbi.nlm.nih.gov/40149917
The Mojave rattlesnake is highly venomous and is found in Southern and Southwestern states. If a person is not treated after being bitten, there is a 30% to 40% chance of death. This rattlesnake’s venom can contain Mojave toxin (MTX), which is a neurotoxin (a substance that damages the nervous system). Using neural cells created from induced pluripotent stem cells (iPSCs; cells that are able to become many different types of cells found in the body), researchers identified the molecular pathways that the venom alters in nervous system cells. The results showed that a type of protein, metalloprotease, found in the venom acts on the extracellular matrix (a substance that surrounds the cells to provide structural support and enhance signaling). MTX triggers multiple cell-signaling cascades, mitochondrial (the structure within a cell that makes energy) toxicity, and cell death. Supported by ORIP (P40OD010960), NHGRI, NHLBI, NIA, and NIGMS.