Glioblastoma multiforme (GBM), the most aggressive primary brain tumor, exhibits high recurrence rates despite multimodal treatment. Recent findings highlight that radiation therapy induces glioma stem cells (GSCs) to transdifferentiate into vascular-like cells through a P300 histone acetyltransferase-mediated mechanism, promoting tumor regrowth via enhanced vascularization. This study investigates this transdifferentiation process using patient-derived GBM cell lines GS34, 390, and 408, which exhibit distinct phenotypic characteristics. Using RT-qPCR analysis, we confirmed that radiation treatment significantly upregulates endothelial and pericyte markers including CDH5, ACTA2, and PDGFRB. Importantly, treatment with P300 inhibitors, carnosol and C646, effectively reduced the expression of these vascular markers post-radiation, particularly at 10μM concentrations. Western blot analysis revealed that carnosol significantly reduced histone H3K27 acetylation compared to controls, while C646 showed differential effects depending on concentration. These findings validate that P300 inhibition counteracts radiation-induced vascular transdifferentiation, suggesting a novel therapeutic approach to prevent GBM recurrence. Future directions include immunocytochemistry validation and lentiviral reporter constructs to visualize this phenotypic conversion in real-time, potentially uncovering new treatments targeting cancer stem cell plasticity.

This study’s primary objective was to determine the identity of the unknown 6753 Sea Urchin gene and clone a portion of the gene for further study. The first steps of the experiment had determined that the unknown 6753 gene encodes for Strongylocentrotus purpuratus Transcription Factor E2F3. A literature review of this gene revealed that the gene was critical for the activation of genes involved in controlling proliferation rates for both normal and tumor cells. The implications of this function make the gene worthwhile to study due to its potential role in tumorigenesis. Analysis of the 6753 gene identity was performed using BLAST and other databases such as InterPro and Echinobase. Following the determination of the gene identity, a phylogenetic tree was created. The gene was then cloned using methods such as PCR, ligation, bacterial transformation, and ending with a confirmation of the results through restriction digests. Following the bacterial transformation and restriction digests, the results could not definitively show that the bacterial colonies contained the correct E2F3 insert due to errors in the gel electrophoresis. The next steps for this experiment would be to redo subsequent steps until the gene was successfully cloned and eventually run further experiments testing loss of function, gain of function, and knockout-rescue experiments.

Muscle Satellite Cells (SCs) are targets for advances in medicine due to their regenerative capacity. SCs, while normally residing in a quiescent state, undergo rapid activation, proliferation, and differentiation upon injury. This regenerative capacity declines with age and disease, making SC transplantation a promising therapy. However, upon isolation and subsequent in vitro culture, SCs activate, losing significant regenerative capacity. Lipid droplets (LDs) are highly dynamic during SC proliferation and differentiation. We previously found that the small molecule inhibitor Atglistatin (ATGLin), which blocks the hydrolysis of triglycerides causing LD accumulation, decreased SC proliferation while increasing resilience, mimicking a quiescent state. We attempted to understand this induced quiescence and the role of LDs in SC activation by supplementing ATGL addition with inhibitors of other enzymes involved in LD metabolism. We tested the ability of SCs to leave ATGLin-induced quiescence and return to the cell cycle, and long-term effects such as toxicity. We found that addition of inhibitors blocking LD formation, or of additional lipids were not sufficient to reverse the effects of ATGL, but that ATGL-treated cells could successfully leave quiescence and re-activate. This indicates that ATGLin could induce reversible quiescence in SCs, but this state is most likely not related to LD metabolism. The ability to keep SCs quiescent after isolation provides a potential therapeutic benefit for transplantation procedures.

Eczema is a chronic inflammatory skin disease that affects millions of individuals, causing patches of excessive itching, redness, and scaliness that cyclically reappear or worsen over time. There is no cure for eczema, but the primary treatment option to manage symptoms is the topical application of glucocorticoids (GC). These steroid hormones are typically used in pharmaceuticals for their anti-inflammatory properties. While GC combats short-term eczema symptoms, long-term usage can cause adverse effects such as skin thinning. Previous research has indicated that GC activates glucocorticoid receptors (GR) encoded by the Nr3c1 gene, which all cell types express. However, because of this ubiquitous GR expression, the cell types targeted by GC remain unclear. This study aims to identify which cell types are most affected by GC treatment for eczema. Using a previously established MC903 model, we induced eczema symptoms in groups of mice knocked out for Nr3c1 in different cell types. Mice lacking GR in myeloid and T cells remained responsive to GC treatment, suggesting neither the adaptive nor innate immune system plays a singular role in the GC eczema pathway. We then confirmed the functionality of the MC903 model in mice lacking GR in keratinocytes, looking ahead to test the role of keratinocytes in GC treatment in our upcoming experiments. Future studies can use these findings to develop novel therapies that mimic the GC mechanism while avoiding the adverse effects of long-term topical steroid usage.