Ketone levels give an insight into the bodies metabolism. People with epilepsy or people dieting may want to keep their levels high, whereas type one diabetics or those recovering from eating disorders may want to keep their levels low. Current ketone detection methods involve blood samples or urinalysis. A ketone (acetone) biosensor was fabricated to detect levels in human breath, providing a noninvasive way to quickly and accurately detect ketone levels in the body.

Redox homeostasis is described as the net physiologic balance between inter-convertible oxidized and reduced equivalents within subcellular compartments that remain in a dynamic equilibrium. This equilibrium is impacted by reactive oxygen species (ROS), which are natural by-products of normal cellular activity. Studies have shown that cancer cells have high ROS levels and altered redox homeostasis due to increased basal metabolic activity, mitochondrial dysfunction, peroxisome activity, as well as the enhanced activity of NADPH oxidase, cyclooxygenases, and lipoxygenases. Glioblastoma (GBM) is the most prevalent primary brain tumor in adults with a median survival of 15 months. GBM is characterized by its extreme resistance to therapeutic interventions as well as an elevated metabolic rate that results in the exacerbated production of ROS. Therefore, many agents with either antioxidant or pro-oxidant mechanisms of action have been rigorously employed in preclinical as well as clinical settings for treating GBM by inducing oxidative stress within the tumor. Among those agents are well-known antioxidant vitamin C and small molecular weight SOD mimic BMX-001, both of which are presently in clinical trials on GBM patients. Despite the wealth of investigations, limited data is available on the response of normal brain vs glioblastoma tissue to these therapeutic interventions. Currently, a sensitive and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method was established for the quantification of a panel of oxidative stress biomarkers: glutathione (GSH), cysteine (Cys), glutathione disulfide (GSSG), and cysteine disulfide in human-derived brain tumor and mouse brain samples; this method will be enriched with additional oxidative stress biomarkers homocysteine (Hcy), methionine (Met), and cystathionine (Cyst). Using this enriched method, we propose to evaluate the thiol homeostasis and the redox state of both normal brain and GBM in mice after exposure with redox-active therapeutics. Our results showed that, compared to normal brain (in intact mice), GBM tissue has significantly lower GSH/GSSG and Cys/CySS ratios indicating much higher oxidative stress levels. Contralateral “normal” brain tissue collected from the mice with intracranial GBM were also under significant oxidative stress compared to normal brains collected from the intact mice. Importantly, normal brain tissue in both studies retained the ability to restore redox homeostasis after treatment with a redox-active therapeutic within 24 hours while glioblastoma tissue does not. Ultimately, elucidating the differential redox response of normal vs tumor tissue will allow for the development of more redox-active agents with therapeutic benefit.

Energy Expenditure (EE) (kcal/day) is a key parameter used to guide obesity treatment, and it is often measured from CO2 production, VCO2 (mL/min), and/or O2 consumption, VO2 (mL/min) through the principles of indirect calorimetry. Current EE measurement technologies are limited due to the requirement of wearable facial accessories, which can introduce errors as measurements are not taken under free-living conditions. A novel contactless system, the SmartPad, which measures EE via VCO2 from a room’s ambient CO2 concentration transients was evaluated. First, SmartPad accuracy was validated by comparing the SmartPad’s EE and VCO2 measurements with the measurements of a reference instrument, the MGC Ultima CPXTM, in a cross-sectional study consisting of 20 subjects. A high correlation between the SmartPad’s EE and VCO2 measurements and the MGC Ultima CPX’s EE and VCO2 measurements was found, and the Bland-Altman plots contained a low mean bias for EE and VCO2 measurements. Thus, the SmartPad was validated as being accurate for VCO2 and EE measurements. Next, resting EE (REE) and exercise VCO2 measurements were recorded using the SmartPad and the MGC Ultima CPXTM at different operating CO2 threshold ranges to investigate the influence of measurement duration on system accuracy in an effort to optimize the SmartPad system. The SmartPad displayed 90% accuracy (±1 SD) for 14–19 min of REE measurement and for 4.8–7.0 min of exercise, using a known room’s air exchange rate. Additionally, the SmartPad was validated by accurately measuring subjects’ REE across a wide range of body mass indexes (BMI = 18.8 to 31.4 kg/m^2) with REEs ranging from ~1200 to ~3000 kcal/day. Lastly, the SmartPad has been used to assess the physical fitness of subjects via the “Contactless Thermodynamic Efficiency Test” (CTET).

The 5-year survival rate for late-stage metastatic melanoma is only ~30%. A major reason for this low survival rate is that one of the most commonly mutated genes in melanoma, NRAS, has no FDA-approved targeted therapies. Because the RAS protein does not have any targeted therapies, patients with RAS mutant tumors have an ongoing need for treatments that indirectly target RAS. This thesis project aims to identify expression and phosphorylation levels of proteins downstream of RAS in melanoma cell lines with the most common driver mutations. By analyzing the protein-level differences between these genetic mutants, we hope to identify additional indirect RAS protein targets for the treatment of NRAS mutant melanoma. RAS has several downstream effector proteins involved in oncogenic signaling pathways including FAK, Paxillin, AKT, and ERK. 5 melanoma cell lines (2 BRAF mutant, 2 NRAS mutant, and 1 designated wildtype) were analyzed using western bloting for FAK, Paxillin, AKT, and ERK phosphorylation and total expression levels. The results of western blot analysis showed that NRAS mutant cell lines had increased expression of phosphorylated Paxillin. Increased Paxillin phosphorylation corresponds to increased Paxillin binding at the FAT domain of FAK. Therefore, cell lines with increased FAK FAT – Paxillin interaction would be more sensitive to FAK FAT domain inhibition. The data presented provide an an explanation for the reduction in cell viability in NRAS mutant cell lines infected with Ad-FRNK. This information also has significant clinical relevance as researchers work to develop synthetic FAK FAT domain inhibitors, such as cyclic peptides. Additionally, cell lines with high levels of phosphorylated AKT showed a significant reduction in the amount of phosphorylated ERK. The identification of this inverse relationship may help to explain why BRAF and NRAS mutations are mutually exclusive. To conclude, NRAS mutant cell lines have increased expression of phosphorylated Paxillin and AKT which may explain why NRAS mutant cell lines are more sensitive to FAK FAT domain inhibition.

Under the direction of Dr. Carolyn Compton, a group of seven Barrett honors students have embarked on a truly unique team thesis project to create a documentary on the process of creating a COVID-19 testing laboratory. This documentary tells the story of the ASU Biodesign Clinical Testing Laboratory (ABCTL), the first lab in the western United States to offer public saliva testing to identify the presence of COVID-19.