Selected Grantee Publications
- 644 results found
In Vivo Prime Editing Rescues Alternating Hemiplegia of Childhood in Mice
Sousa et al., Cell. 2025.
https://pubmed.ncbi.nlm.nih.gov/40695277
Alternating hemiplegia of childhood (AHC) is a neurodevelopmental disease that can cause involuntary muscle contractions, low muscle tone, paralysis on one side of the body, abnormal eye movements, seizures, and intellectual disability. There is currently no treatment. AHC is caused by a mutation in the gene ATP1A3; three variations of the ATP1A3 gene mutation are responsible for 65% of cases. Researchers used prime editing and base editing tools to correct ATP1A3 gene mutations in cells isolated from AHC patients and two mouse models for AHC (sex not specified). Results showed that physical characteristics of AHC were corrected and that treated mice had an extended lifespan. These findings support the potential use of prime editing and base editing tools to treat a neurological disease. Supported by ORIP (U54OD030187, U42OD010921), NHGRI, NIGMS, and NINDS.
Advances in Host-Directed Therapy for Tuberculosis and HIV Coinfection: Enhancing Immune Responses
Prasanna et al., Trends in Microbiology. 2025.
https://pubmed.ncbi.nlm.nih.gov/40345900
A quarter of the world’s population is infected with Mycobacterium tuberculosis (Mtb); however, 90% to 95% of people with Mtb are asymptomatic (meaning they do not show symptoms) and are considered to have LTBI (latent tuberculosis [TB] infection). People with immunosuppressive conditions, such as HIV, however, are at higher risk for symptomatic TB that can spread to other organs beyond the lungs. When people with Mtb become infected with HIV, Mtb-specific CD4+ T cells are reduced, and inflammation is increased from chronic immune cell activation. This promotes the progression of TB. Coinfected people also can suffer from drug-resistant infection, drug toxicity, or incomplete pathogen clearance, which highlights the need for additional therapies. To potentially improve clinical outcomes of HIV and TB coinfection, host-directed therapy (HDT) has emerged as a promising addition to current treatments. This review discusses several kinds of HDTs—including cytokine therapy, chimeric antigen receptor T-cell (CAR T-cell) therapy, and immune checkpoint inhibitors. HDTs restore normal immune cell function and minimize inflammation. This review highlights the potential use of HDTs with current HIV and TB therapies to reduce the prevalence of coinfection. Supported by ORIP (K01OD031898) and NIAID.
Dia–B–Ties: B Cells in the Islet–Immune–Cell Interface in T1D
Hilliard et al., Biomolecules. 2025.
https://pubmed.ncbi.nlm.nih.gov/40149868
Roughly 30 million people worldwide suffer from type 1 diabetes (T1D). T1D is an autoimmune disease that requires lifelong use of insulin. A key feature of T1D is T cell–driven damage of insulin-producing β islet cells in the pancreas. This review discusses the role of B lymphocytes (an immune cell) in T1D disease development and progression. B lymphocytes are an essential mediator of communication between other immune cell types and islet cells in what is known as the islet–immune interface. B lymphocytes coordinate communication among different cell types through antigen (a substance that tells your immune system whether something is harmful) presentation, cytokine secretion, and antibody production. Using these methods, B lymphocytes activate autoreactive (an antibody that targets a normal molecule within a person) T cells that target islet cells, which amplifies inflammation in the pancreas during the initial stages of T1D development. The review outlines current and potential therapies that target B lymphocytes. These therapies potentially could be beneficial in T1D treatment. Supported by ORIP (K01OD028759, R03OD036470) and NIAID.
Acute Degradation of Nucleolin Reveals Its Novel Functions in Cell Cycle Progression and Cell Division in Triple Negative Breast Cancer
Mills et al., Journal of Experimental and Clinical Cancer Research. 2025.
https://pubmed.ncbi.nlm.nih.gov/40653460
The nucleolus is a vital compartment within the cell where ribosomes (which link amino acids together to form proteins) are assembled. Traditional experimental methods cannot deplete nucleolar proteins (proteins that make up the nucleolus) while keeping the cell alive, which limits our understanding of the biological functions of these proteins. Researchers used two advanced techniques to successfully deplete and identify the biological functions of nucleolin (NCL) in triple-negative breast cancer (TNBC) cells. NCL is one of the most abundant nucleolar proteins in the body. Results showed that depleting NCL in TNBC cells causes defects in cytokinesis, a step in cell division. Defects in cell division result in a smaller increase in TNBC cell numbers. Cancer therapies that target cellular mitosis (the process of a single cell dividing into two new cells) were more useful when NCL was degraded. This research supports a new role of NCL in TNBC cell division and reveals that inhibiting NCL may enhance cancer therapies. Supported by ORIP (K01OD031811) and NCI.
The Atypical Quorum Sensing System of Classical Brucella Species
Caudill and Caswell, 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.