Adaptive therapy is a novel up-and-coming cancer treatment strategy to minimize chemoresistance in cells to improve patient prognosis. The standard of care cancer treatment has a fixed linear approach known as Maximum Tolerated Dose (MTD) which promotes an exponential growth of resistant cancer cell populations in the tumor. Through this treatment procedure, a population of chemoresistant cells resurges, decreasing the survival in patients, and narrowing potential treatment options (Gatenby). An assortment of chemotherapeutic drugs and dosing schedules were tested on ER+ endocrine-resistant MCF7 breast cancer cells in an immunodeficient mouse model. After the cessation of treatment, some mouse models’ tumors remained stable or began to shrink. Several immunodeficient mouse models have indicated unexpectedly high levels of neutrophils stemming from an unknown origin. We aim to understand if neutrophils' innate immunity may affect tumor size post-chemotherapy treatment and if it has therapeutic implications along with adaptive therapy. MCF7 breast cancer tumors were extracted from the mice, embedded in wax, and sliced, and immunofluorescence was performed to detect neutrophils and nuclear components. Currently, the protocol is in its third round of optimization.

Autism spectrum disorder (ASD) currently lacks a biological diagnostic test, ongoing research is being conducted to develop a urine biomarker test for autism. Researchers are investigating possible anions, such as sulfur-based anions, as a biomarker for autism. Although studies have not measured the quantification of sulfate-based anions within a biospecimen while using Ion Chromatography (IC) for a 24-hour period. Research studies on autism biomarker development could greatly benefit by investigating and quantifying sulfur-based anions such as sulfate, sulfide, sulfite, or thiosulfate. Our research investigated the quantifications of anions through the analysis of biospecimens across 24-hours in an IC. The results of our research indicate that sulfate fluctuates the least and was consistently read by the IC at each time point across 24 hours whereas the other anions of interest presented greater fluctuations and were not detected at each time point across the 24 hours under the conditions tested.

The kynurenine pathway (KP) is a biosynthetic pathway for the catabolism of tryptophan, the amino acid precursor to serotonin. The KP has been linked to neuroinflammation, as inflammatory agents upregulate an early enzyme in the pathway (Davis & Liu, 2015; Wang et al., 2009). In addition, the metabolite quinolinic acid (QA) has been found to induce tau phosphorylation and excess glutamate release, inducing further neuroinflammation (Guillemin, 2012; Rahman et al., 2009). However, in the presence of 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase (ACMSD), the KP shifts away from QA production towards that of picolinic acid (PA), a metabolite with antimicrobial and antiviral properties. Our lab has previously shown that overexpressing ACMSD via adeno-associated virus (AAV) delivery in the alpha-synuclein (α -syn) model of Parkinson's disease (PD) animal model exhibits neuroprotective effects by preventing the loss of dopaminergic neurons in the substantia nigra and limiting motor impairments caused by nigrostriatal denervation. Based on these findings, we predicted that ACMSD would provide neuroprotective effects in the P301S tauopathy model of neurodegenerative disease, a mouse model of frontotemporal dementia (FTD). Specifically, we hypothesized that ACMSD would ameliorate behavioral deficits, including those related to cognitive and emotional processing. We also predicted that ACMSD overexpression would prevent histological indices of pathology, including the expression of hyperphosphorylated tau, gliosis, and neurodegeneration. As previous findings in the literature have denoted sex differences in pathological outcomes of the P301S mouse model (Sun et al., 2020) with males showing more pronounced behavioral deficits and increased hyperphosphorylated tau than females, we hypothesized that ACMSD would show a higher degree of neuroprotection in male P301S mice. P301S and litter/age-matched wild-type controls underwent stereotaxic surgery at two months of age prior to pathological onset to deliver either an AAV-dHS-ACMSD or AAV-dHS-GFP (control) to the dorsal hippocampus. Prior to euthanasia, the mice underwent the Barnes maze test to assess cognitive function focusing on learning and memory recall. Analysis of this assay revealed that male P301S mice treated with ACMSD displayed a trend toward shorter latency in locating the escape hatch during the Barnes Maze test than untreated males, albeit not significant, suggesting a potential enhancement in spatial learning. At eight and a half months, the mice were killed, and their brains harvested. The tissue underwent immunohistochemistry staining for a marker of hyperphosphorylated tau (AT8), markers of gliosis (Iba1 and GFAP), and the pan-neuronal marker (HuC/D) to quantify pathological indices. Preliminary histological analyses show decreased immunoreactivity of AT8 in the hippocampus of P301S mice injected with ACMSD, compared to those injected with GFP control, indicating potential neuroprotective effects by limiting the amount of hyperphosphorylated tau.

Medulloblastoma is the most common pediatric brain cancer and accounts for 20% of all pediatric brain tumors. Upon diagnosis, patients undergo tumor-resection surgery followed by intense chemotherapy and cerebrospinal irradiation (CSI) regimens. CSI therapy is highly toxic and poorly tolerated in pediatric patients and is known to cause long-term neurocognitive, endocrine, and developmental deficits that often diminish the quality of life for medulloblastoma patients. The development of targeted therapies is necessary for both increasing the chance of survival and reducing treatment-related morbidities. A potential therapeutic target of interest in medulloblastoma is the polyamine biosynthesis pathway. Polyamines are metabolites present in every living organism and are essential for cellular processes such as growth, survival, and differentiation. Recent studies have shown that polyamine production is dysregulated in several cancers, including brain cancers, and have highlighted polyamine biosynthesis as a potential cancer growth dependency. Dysregulated polyamine metabolism has also been linked to several oncogenic drivers, including the WNT, SHH, and MYC signaling pathways that characterize genetically distinct medulloblastoma subgroups. One way to target polyamine biosynthesis is through the inhibition of the rate-limiting enzyme ornithine decarboxylase with difluoromethylornithine (DFMO), an analog of the polyamine precursor ornithine. DFMO is well-tolerated in pediatric populations and exerts minimal toxicities, as shown through neuroblastoma clinical trials, and is a therapy of interest for medulloblastoma. While DFMO has been tested clinically in multiple cancers, few in vitro studies have been performed to understand the exact mechanisms of anti-proliferation and cytotoxicity. Our study screened two immortalized medulloblastoma cell lines, DAOY (SHH) and D283 (non-WNT/non-SHH), and three patient-derived medulloblastoma cell lines, SL00024 (SHH), SL00668 (non-WNT/non-SHH), SL00870 (Unknown subgroup), for DFMO sensitivity and profiled the immortalized medulloblastoma cell line metabolome to understand the interactions between inhibition of polyamine metabolism with other essential metabolic processes and tumor cell growth. We found that medulloblastoma cell lines are sensitive to DFMO and the adaptive response to DFMO in medulloblastoma may be caused by increased oxidative stress and free radical scavenging. Our study hopes to inform the use of DFMO as an anti-cancer therapy in medulloblastoma by understanding the drug’s single-agent anti-proliferative mechanisms.

This thesis/creative project involved writing a collection of creative nonfiction essays and building a website to reflect on my experiences traveling through Spain in the summer of 2023, for both a study abroad program and on my own. There are a total of nine essays in this current collection, along with a tenth introductory essay. They reflect the chronological order of my travels to Madrid, Sevilla, Granada, Valencia, Barcelona, and Lisbon, concluding with an essay written about my return to Phoenix, Arizona. The goal of this project was to not only personally reflect on what I learned while in these various places, but also to share these experiences with a wider audience in the digital world. I plan to continue adding essays to this website, using it as a "living document" for my future travels, and as a place for further reflection.

Oral health encompasses a wide variety of conditions with two of the primary conditions being enamel degradation and periodontal disease. These ailments are intertwined and are known to be prevented by a combination of good oral hygiene and a balanced diet. Despite this, incidence rates of oral health conditions in both high and low-and-middle income countries remain high. Periodontal disease prevention is of particular relevance due to its correlation with cardiovascular disease. One highly popular diet that could serve as an alternative strategy in combatting these oral health conditions is intermittent fasting. Intermittent fasting has shown promise in decreasing systemic inflammation and blood glucose levels, both of which are correlated with periodontal disease and enamel degradation. To explore this relationship between intermittent fasting and oral health a 9-week experimental protocol with 4 randomly established groups was completed. These groups included ad libitum high and low-fat groups, and time restricted feeding high and low-fat groups. After the 9-week protocol the mice were sacrificed, and their intact jaws and gingiva tissue were isolated. Three primary methods were used to quantify the effects of intermittent fasting on oral health: comparing the enamel density between groups, comparing the alveolar bone recession between groups, and comparing the gene expression of periodontal disease markers between groups. Body composition and fasting blood glucose levels of the mice were also quantified. We found that the fasting groups had lower average fasting blood glucose levels and maintained a more physiologically ideal body composition. Despite this, the oral health analyses did not have any consistent significant results. The results of this study suggest that despite intermittent fasting’s role in blood glucose levels and body composition regulation, it has minimal effects on enamel degradation and periodontal disease development.

In 2019, 20.4 million people in the United States were diagnosed with SUDs, and only 10.3 percent of those diagnosed received SUD treatment [1]. Addiction Consult Services in the inpatient setting provide an opportunity for diagnosis and treatment. An ACS is a multidisciplinary team which offers specialized care for those with SUDs, often including initiation of medication treatment, linkage to outpatient clinics and resources, and patient counseling [2]. We sought to conduct a systematic review and partial meta-analysis on the impact of Addiction Medicine Consult services in the inpatient setting on patients with SUDs.