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.

After traveling to Spain to study abroad, I noticed a large amount of shops selling goods related to Japanese anime, which helped inspire the topic of my honors thesis. In this paper, the cultural impact of Japanese animation and comics on Spain is explored. The history/origin of anime in Spain, the early reception of these works in Spain, the importance of the anime fandom, the intersection between Spanish and Japanese culture in anime and anime-inspired films, and the positive representation of Spain in these works are all relevant topics that constitute the argument of this document. Sources in both English and Spanish are utilized.This paper explores the surprising connections between the two countries. The way in which their cultures interact through the consumption of this form of media was quite fascinating to look into.

Histology, the microscopic examination of tissues, is a pivotal tool in research. By providing a detailed view of cellular structures and their organization, this technique allows researchers to advance knowledge in many different disciplines including women’s health and ovarian studies. Studying the female reproductive system is of utmost importance due to its multifaceted effects on aspects such as biological functions, cellular mechanisms, and complex behavioral patterns in women. Therefore, the aim of this honors thesis is to refine and adapt a set of protocols from the Mayer-Dyer Laboratory for ovarian and follicular processing so that they are optimal to use in the Bimonte-Nelson Laboratory of Memory and Aging in the Department of Psychology at Arizona State University. The subsequent aim for the thesis is to replicate and extend the new protocols to complete histology of the ovaries from an interdisciplinary study that evaluated the consequences of hysterectomy with and without estrogen replacement for brain and cognition. This dual-pronged approach will not only contribute to the ongoing discussion regarding the effects of hysterectomy, but also provides a valuable framework for future research endeavors in the field.

Cell immunotherapies have revolutionized clinical oncology. While CAR T cell therapy has been very effective in clinical studies, off-target immune toxicity limits eligible patients. Thus, NK cells have been approached with the same therapy design since NK cells have a more favorable safety profile. Therefore, the purpose of this research project is to explore DNA nanotech-based NK cell engagers (NKCEs) that force an immunological synapse between the NK cell and the cancer cell, leading to cancer death. DNA tetrabody (TB) and DNA tetrahedron (TDN) are fabricated and armed with HER2 affibody for tight adhesion to HER2+ cancer cell lines like SKBR3. Overall, relationship between TB-NK treatment and cancer cell apoptosis is still unclear. TB-NK treatment induces an apoptotic profile similar to PMA/IO stimulation. Pilot cell assay needs to be replicated with additional controls and a shortened treatment window. For DNA TDN fabrication, HER2 affibody polishing with Ni-NTA affinity chromatography achieves high purity with 20% to 100% high-imidazole elution gradient. ssDNA-HER2 affibody conjugation is optimal when ssDNA is treated with 40-fold excess sulfo-SMCC for 4 hours. In conclusion, the manufacturing of DNA-based NKCEs is rapid and streamlined, which gives these NKCEs the potential to become a ready to use immunotherapy.

This thesis outlines the four novels of my fantasy series in-progress, entitled Pemoki and Kenacia (named for two nations engaged in a twenty-year conflict). It details the complex workings of the universe in which the series takes place, and seeks to capture the essence of the characters’ journeys through a number of fictional texts exchanged within the universe, which I refer to as “writing within writing”. It includes a guide containing notes on the international and domestic politics, religions, technologies, magic system, and invented languages of the P&K universe; four extensive plot summaries complete with dialogue; eight instances of writing within writing, including four collections of letters, a coronation speech, two articles in conversation with one another on the subject of magic science, and a series of journal entries documenting an investigation of a suspected foreign spy; and finally, an appendix listing the names and magical abilities of the cast, as well as the fictional locations they inhabit. “Writing Within Writing” lays the groundwork for a tetralogy that, in its final published form, will explore themes of corruption, redemption, free will, death, grief, endurance, love and betrayal, among others.

Heterotrophs such as E. coli contain metabolic pathways with enzymes called carboxylases that are capable of fixing CO2 gas to form metabolites, which has implications for aiding with CO2’s role in climate change. The reductive branch of the tricarboxylic acid (TCA) cycle serves as an important pathway for NAD+ regeneration in enteric bacteria in anaerobic conditions and leads to the production of succinate, a useful industrial product. The enzyme phosphoenolpyruvate carboxykinase is responsible for fixing CO2 in the conversion of PEP to OAA within this pathway and has potential to be a significant carbon fixation module in heterotrophic organisms. This project explored pck genes from select organisms by transforming plasmids to test if these variants have improved kinetics compared to the native E. coli Pck and to investigate their ability to improve succinate bioproduction.