IDH1-mutant gliomas are a distinct subset of diffuse brain tumors characterized by altered metabolism and an immunosuppressive tumor microenvironment (TME). Although mutant IDH inhibitors have emerged as a promising therapy, their effects on tumor–immune interactions and spatial organization remain unclear.In this study, multiplex immunofluorescence staining and CO-Detection by indEXing (CODEX) imaging were used to generate high-dimensional spatial data from formalin-fixed paraffin-embedded (FFPE) glioma specimens obtained from patients with IDH1-mutant tumors across multiple tumor resections. We investigated changes in cellular composition and spatial organization during treatment by analyzing a panel of tumor, immune, and macrophage markers to characterize cellular composition, spatial distribution, and cell–cell interactions across treatment exposure. Spatial analysis revealed marked heterogeneity in immune infiltration and tumor architecture. Tumor-enriched regions showed immune exclusion, while post-treatment samples exhibited increased immune infiltration, including macrophage accumulation and elevated expression of immune regulatory molecules. These findings suggest that IDH1 inhibitor treatment remodels the glioma TME, where increased immune presence may be accompanied by adaptive immune suppression. This work highlights the value of spatial approaches such as CODEX in understanding therapeutic response and identifying targets to improve immunotherapy for IDH1-mutant gliomas.

Toxoplasma gondii is an intracellular parasite that infects a large portion of the global population and can cause severe disease in immunocompromised individuals. Although kinases are critical regulators of parasite biology, many remain uncharacterized. This study investigates a novel kinase, K370, which displays cell cycle-dependent expression and localizes to daughter buds during parasite replication. To determine its function, endogenous tagging and immunofluorescence assays were used to examine K370 localization. A CRISPR/Cas9 knockout strain was generated to assess its role in parasite development. Loss of K370 resulted in abnormal morphology, defective daughter cell segregation, and reduced parasite viability. Functional assays demonstrated significant defects in invasion and growth. These findings suggest that K370 is essential for proper daughter cell formation and parasite replication. Understanding its role provides insight into the molecular mechanisms underlying the T. gondii lytic cycle and highlights K370 as a potential target for therapeutic intervention.

This abstract has been withheld from publication.

Premenopausal women have a lower incidence of cardiovascular disease than age-matched men. This sex-specific protection is lost after menopause, a shift that has been attributed to declining estrogen levels. Estrogen receptor alpha (ERα), encoded by the Esr1 gene, is a nuclear transcription factor that binds estrogen and plays a pivotal role in regulating mitochondrial function in cardiomyocytes. We hypothesize that ERα signaling is required for normal cardiac function, and its loss contributes to the increased cardiovascular risk observed after menopause. To test this, our lab has developed cardiomyocyte-specific Esr1 knockout and overexpression mouse models using the tamoxifen-inducible Cre/loxP system. This system allows for precise temporal control over Esr1 expression to mimic the mid-life loss of estrogen signaling that occurs during menopause. Our findings show that Esr1 knockout mice have reduced cardiac function compared to controls, including lower ejection fraction (a measure of how well the heart pumps), reduced fractional shortening (a measure of heart contractility), and increased cardiac fibrosis. These findings establish ERα as necessary for maintaining cardiac integrity. We are now investigating whether Esr1 overexpression has cardioprotective effects, with ongoing work to validate the cardiomyocyte-specific overexpression. Ultimately, this research will help clarify the role of ERα in cardiac health and identify ERα-related pathways as potential therapeutic targets, particularly for postmenopausal women.

In tumor cells, the oxygen levels are often lower than normal cells, which can influence both tumor cells and supporting stromal cells such as mesenchymal stem cells (MSCs). Understanding MSC responses to hypoxic conditions is relevant for improving in vitro models of the tumor microenvironment. This study investigates the impact of different oxygen concentrations on the growth of MSCs. To model this, MSCs are cultured under normoxic (21% O₂) and hypoxic (5% O₂) conditions with different assays. Three-dimensional tumor spheroids are generated to better mimic the tumor microenvironment. Cell growth, viability, morphology, and immune-mediated cytolytic activity are analyzed using microscopy and flow cytometry. MSCs are also evaluated for clonogenic potential and spheroid formation under various oxygen conditions. Results are compared and analyzed between hypoxic and normoxic conditions to determine how oxygen levels affect tumor progression and immune response. It’s expected that hypoxic conditions will alter and lead to better MSC growth behavior, viability, and spheroid formation. This study improves the understanding of how MSCs respond to low-oxygen conditions within the tumor microenvironment and may help guide future strategies for treating hypoxic tumors.