Progesterone and estrogen, two endogenous steroid hormones, play a crucial role in reproductive processes. With their similarities in hormone structure and cellular signaling mechanisms, the two hormones are also involved with the growth of hormone-receptor-positive breast cancers, acting as agonists to enhance cell proliferation. However, little research has examined whether progesterone specifically influences estradiol signaling and transcriptional responses. To determine whether progesterone affected estradiol signaling, the Cell SeeER V2 tool was used to measure estradiol signaling through the presence of red and green fluorescent markers in human embryonic kidney cells (HEK293T cells). The cells were transfected with various combinations of the progesterone receptor, estrogen receptor alpha (ERα), and the Cell SeeER V2 reporter and administered estradiol and progesterone hormones. When wells containing both estrogen and progesterone receptors were treated with hormone, progesterone downregulated estradiol signaling as evidenced by a decrease in green fluorescence intensity. While the specific mechanisms of how progesterone produces this downregulatory effect remain unclear, future directions may include repeating the experiment under breast cancer cell lines to further examine the relationship between the two hormones.

Clear cell renal cell carcinoma (ccRCC) frequently progresses to metastatic disease, which is associated with poor patient outcomes and limited treatment options. Recent work has shown that tumor heterogeneity, particularly cooperative interactions between VHL⁺ and VHL⁻ cell populations, drives metastasis, with VHL⁻ cells acting as metastatic drivers. Building on prior high-throughput screening results identifying statins as selective inhibitors of VHL⁻ cells, this study investigates whether these effects translate to human ccRCC models and explores the underlying mechanism. Using engineered 786-O human ccRCC cell lines (VHL⁺, VHL⁻/HIF-1α⁺, and VHL⁻/HIF-2α⁺), colony formation assays were performed following treatment with both older and newer statins across a range of concentrations. After crystal violet staining, colony growth was quantitatively analyzed by measuring colony area using MATLAB-based image analysis, enabling direct comparison of cell survival across conditions. We hypothesize that older statins (simvastatin, lovastatin, and fluvastatin) will selectively inhibit VHL⁻ cells through a HIF-dependent mechanism, while newer statins will show minimal effects. Furthermore, comparing HIF-1α and HIF-2α–specific variants will help identify which hypoxia pathway mediates statin sensitivity. Overall, this study aims to validate statins’ selective anti-metastatic effects in human ccRCC and identify their molecular target, supporting their potential repurposing as anti-metastatic therapies.

Tetrodotoxin (TTX) is a neurotoxin that acts as the primary method of defense for the rough-skinned newt (Taricha granulosa). In most animals, TTX causes fatal respiratory paralysis by blocking voltage-gated sodium (Nav) channels, preventing action potentials from firing; however, T. granulosa shows immunity to TTX. In this study, we investigated the auto-resistance strategies employed by T. granulosa. We tested whether resistance is supported by toxin sequestration, in which proteins bind and sequester TTX, by mutations in sodium channels, or by a combination of both. Behavioral tests confirmed that T. granulosa is resistant to TTX while the axolotl (Ambystoma mexicanum), a toxin-free control, was not. Electrophysiology experiments showed that previously identified T. granulosa Nav1.4 TTX resistant mutations only provided partial TTX resistance in human Nav1.4 channels, suggesting that channel mutation alone is insufficient. Liver soluble proteins from T. granulosa and A. mexicanum were isolated and separated using Liquid Chromatography (FPLC), which showed a distinct peak fraction present only in the newt samples. However, this fraction failed to provide TTX resistance to sodium channels. These results suggest that additional sodium channel mutations and/or membrane bound toxin-binding proteins are required to defend against TTX, and future investigations will aim to identify such proteins or mutations. Ultimately, these studies may help the development of antidotes and biosensors for detecting TTX and other deadly toxins.

Aging is accompanied by progressive loss of muscle mass and function, closely linked to metabolic dysregulation. Although age-related atrophy disproportionately affects type II muscle fibers, it remains unclear whether metabolic pathways are differentially regulated across fiber types during aging. This study examined fiber type–specific regulation of glucose metabolism and whether late-life exercise training (ExTR) can restore metabolic function. Using stable isotope tracing, young and aged mice, with or without a 6-week ExTR, received intravenous 13C-glucose to quantify labeling of glycolytic and tricarboxylic acid (TCA) cycle intermediates in soleus (type I) and quadriceps (type II) muscles via LC-MS–based metabolomics. In aged mice, glycolytic intermediates, including hexose phosphates and pyruvate, exhibited elevated labeling from glucose across muscle types compared to young mice. This elevation was selectively attenuated by ExTR in quadriceps. While TCA cycle intermediate labeling including succinate were unchanged in soleus with aging, these were increased in quadriceps, with partial normalization following ExTR. These results demonstrate that alterations in glycolysis and TCA cycle metabolism are more pronounced in type II fibers, and that ExTR preferentially restores metabolic function in these fibers. Overall, this work identifies a distinct pattern of metabolic dysregulation across muscle types and highlights the potential of late-life ExTR to mitigate age-related metabolic decline in skeletal muscle.

Focal amplifications (FAs) are an increase in oncogene copy number that often confer cancer cell resistance to drugs. Lipid profiling of vemurafenib + selumetinib resistant ecDNA and Homogeneously Staining Region (HSR) FAs suggests extra sensitivity to lipid peroxidation inhibition through the inhibition of GPX4, a key regulator of ferroptosis sensitivity. Along with analysis of the upstream inhibition of the SREBP1/2 pathways, confirmation of the sensitivity of ecDNA and HSR FAs in M249 melanoma cells is vital to understanding and promoting ferroptosis in these drug-resistant cancer cells. This can be performed through measures of cell sensitivity to oxidative stress related to GPX4’s glutathione dependent lipid hydroperoxide and ferroptosis regulatory features.