Selected Grantee Publications
- 595 results found
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.
In Utero Rescue of Neurological Dysfunction in a Mouse Model of Wiedemann-Steiner Syndrome
Reynisdottir et al., JCI Insight. 2025.
https://pubmed.ncbi.nlm.nih.gov/40956618
Wiedemann-Steiner syndrome (WDSTS) is a rare, autosomal dominant (only one mutated gene copy is needed for symptoms to develop) genetic disorder that causes intellectual disability, abnormal facial features, and reduced growth. WDSTS occurs when the histone lysine methyltransferase 2A (KMT2A) protein is mutated. In previous studies using mouse models, syndromes related to WDSTS, such as Rett and Kabuki, have shown promise in being treatable after birth. The researchers created a mouse model for WDSTS (both sexes used) and showed that the genetic disorder could be treated in the womb by restoring KMT2A protein function. This model could be used in future studies to identify possible therapies and the window for treatment. Supported by ORIP (U54OD030187).
Structural and Functional Basis of Mechanosensitive TMEM63 Channelopathies
Zheng et al., Neuron. 2025.
https://pubmed.ncbi.nlm.nih.gov/40480214
Mechanotransduction occurs when cells sense changes in outside physical forces and convert them into electrical or chemical signals. To complete this process, certain ion channels are used, such as transmembrane protein 63A (TMEM63A), to pass ions and fats across cell membranes. TMEM63B and TMEM63C are part of the same protein family as TMEM63A. Mutations in these three channels cause neurodevelopmental disorders. Researchers identified the changes in protein structure and function for common TMEM63A and TMEM63B mutations. The results provide insight into TMEM63 channel dysfunction. Supported by ORIP (R21OD037849), NIDCD, and NIGMS.
Estimating Realized Relatedness in Free-Ranging Macaques by Inferring Identity-by-Descent Segments
Freudiger et al., PNAS. 2025.
https://pubmed.ncbi.nlm.nih.gov/39808663
Biological relatedness is a key consideration in studies of behavior, population structure, and trait evolution. Except for parent–offspring dyads (pairs), pedigrees (diagrams that show family member relationships) do not capture individual relatedness perfectly. The number and length of identical-by-descent (IBD) segments of DNA yield the most precise estimates of being related. The researchers used different methods to estimate IBD segments in free-ranging rhesus macaques (both sexes used). Then, they compared the IBD-based estimates to current methods, such as pedigree. The results show that IBD-based estimates are more reliable and provide more detailed information about relationships. Future population studies can use this accurate method to investigate predictors and consequences of being genetically related in natural populations. Supported by ORIP (P40OD012217, P51OD011092), NHGRI, NIA, and NIMH.
A STAT3/Integrin Axis Accelerates Pancreatic Cancer Initiation and Progression
Campos et al., Cell Reports. 2025.
https://pubmed.ncbi.nlm.nih.gov/40701148
In pancreatic ductal adenocarcinoma (PDAC), inflammation and cell stress within the environment surrounding the tumor are known to promote cancer cell growth and increase drug resistance. The signal transducer and activator of transcription 3 (STAT3) pathway directs these responses. Researchers used human cancer cells and mouse models for PDAC (both sexes used) to identify binding sites of STAT3 that regulate gene expression and are linked to poor survival. The results showed that STAT3 interacts with integrin beta 3 to start and grow PDAC tumors. STAT3 also targets 18 genes that are involved in adaptive responses and can be used to identify different survival outcomes. This study highlights a new way to classify PDAC subpopulations for STAT3-targeted therapies. Supported by ORIP (K01OD030513), NCI, and NIGMS.
Advances in Targeted Autophagy Modulation Strategies to Treat Cancer and Associated Treatment-Induced Cardiotoxicity
Ling et al., Pharmaceuticals (Basel). 2025.
https://pubmed.ncbi.nlm.nih.gov/40430490
Millions of cancer patients and cancer survivors face an increased risk of developing cardiotoxicity and cardiovascular (system encompassing the heart and blood vessels) dysfunction because of cancer progression and cancer treatments. Irregular autophagy causes this increased risk. Autophagy is the breakdown of old, damaged, or abnormal proteins within the cell that are then recycled for use in other proteins. Managing autophagy could protect the cardiovascular system during cancer treatment. This review notes the advances in regulating autophagy and how it could be applied to treat cardiotoxicity while improving cancer treatment outcomes. The researchers highlight in vitro (outside a living organism) models and other tests to discover solutions that can allow autophagy therapies to be translated into the clinic. Supported by ORIP (K01OD028205) and NHLBI.
Microbiome and Metabolome Association Network Analysis Identifies Clostridium_sensu_stricto_1 as a Stronger Keystone Genus Candidate Than Bifidobacterium in the Gut of Common Marmosets
Hernandez et al., mSystems. 2025.
https://pubmed.ncbi.nlm.nih.gov/40622159
The common marmoset is a nonhuman primate model for microbiome (the collection of microorganisms found in the body) studies. Previous studies have shown significant variation in the gut microbiome among individual common marmosets due to such factors as diet, age, sex, and captivity. Researchers identified how the gut microbiome and metabolome (the collection of molecules made or used during the chemical processes of a cell) change over time using fecal samples collected from 1- to 9-year-old healthy, captive marmosets of both sexes. Results showed that certain bacteria have a stronger influence within the gut than others. Bifidobacterium was the most abundant genus (a higher level of classification than species) of bacteria and the driver of microbiome differences among individual marmosets. Also, the results suggest that Bacteroidales bacteria compete with Bifidobacterium for resources within the gut. The researchers created a Keystone Candidate Score to identify the most influential bacteria, which were Clostridium_sensu_stricto_1 and Alloprevotella. This study provides insight into how the microbiome—including interactions among different bacteria and competition for resources—affects the health of common marmosets in captivity. Supported by ORIP (K01OD030514) and NIGMS.
Sequencing Analysis Demonstrates That a Complex Genetic Architecture Contributes to Risk for Spina Bifida
Strain et al., Birth Defects Research. 2025.
https://pubmed.ncbi.nlm.nih.gov/41013918
Neural tube defects (NTDs) are defects of the brain, spinal cord, or spine. NTDs are the second most common type of congenital birth defect worldwide. Nucleotides are building blocks that are combined in a sequence to make DNA or RNA. Although prior studies have identified rare, harmful single nucleotide variants (SNVs) in spina bifida, broader contributions to risk remain unclear. Researchers analyzed genetic risk among 256 probands (individuals affected by the genetic disorder) compared with 395 ancestry-matched healthy controls (sex not specified). Results from their analyses identified 16 genes associated with spina bifida. Four genes were enriched in the parents, which supports the idea of inherited risk for spina bifida. This study provides insight into the many SNVs that can cause spina bifida and highlights the complex origin of the genetic disorder. Supported by ORIP (U54OD030187), NICHD, NIGMS, and NINDS.