Barrett, The Honors College Thesis/Creative Project Collection
Barrett, The Honors College at Arizona State University proudly showcases the work of undergraduate honors students by sharing this collection exclusively with the ASU community.
Barrett accepts high performing, academically engaged undergraduate students and works with them in collaboration with all of the other academic units at Arizona State University. All Barrett students complete a thesis or creative project which is an opportunity to explore an intellectual interest and produce an original piece of scholarly research. The thesis or creative project is supervised and defended in front of a faculty committee. Students are able to engage with professors who are nationally recognized in their fields and committed to working with honors students. Completing a Barrett thesis or creative project is an opportunity for undergraduate honors students to contribute to the ASU academic community in a meaningful way.
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Description
Heron Lodge is the hybrid product of sciences, (pre) medicine, and the humanities throughout four years of an undergraduate degree in Medical Studies.
ContributorsLu, Emilie Joy (Author) / Dombrowski, Rosemarie (Thesis director) / Viren, Sarah (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Non-small cell lung cancer (NSCLC) has become the leading cause of cancer-related deaths in the United States with a combined 5-year survival rate of only 16%. Even with advancements in aggressive chemotherapeutics, there has been little improvement in patient survival. LKB1 (liver kinase B1)/STK11 (serine-threonine kinase 11) is a tumor suppressor gene mutated in ~30% of NSCLC adenocarcinomas and loss of LKB1 is associated with a more aggressive cancer phenotype. In LKB1-deficient NSCLC, we observe significantly elevated expression and secretion of the chemokines CCL2, CCL5, and CCL20, which are involved in macrophage recruitment. Numerous studies have shown that high infiltration of a unique subset of macrophages called tumor-associated macrophages (TAMs) is associated with poor prognosis in patients with various cancers. mTORC1-HIF1-α and NFκB are two pathways that have been shown to regulate chemokine secretion and are often up-regulated in the absence of LKB1. Dosing LKB1-null cell lines with inhibitors of mTOR and NFκB in addition to silencing HIF1-α gene expression demonstrate that NFκB but not mTORC1-HIF1-α signaling may play a role in regulating chemokine secretion in LKB1-deficient NSCLC. Collectively, these results provide insight into the mechanisms responsible for the aggressive phenotype associated with LKB1-deficient non-small cell lung cancer.
ContributorsO'Brien, Kelley Xiao-Fung (Author) / Blattman, Joseph (Thesis director) / Inge, Landon (Committee member) / Friel, Jacqueline (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Among wild rodent populations, vertical transmission is believed to constitute the primary route of infection for Lymphocytic Choriomeningitis Virus (LCMV), a non-lytic arenavirus with both acute and chronic forms. When carrier mice infected at birth with the acute Armstrong strain reproduce, they generate congenital carrier offspring containing a quasispecies of LCMV that includes Armstrong as well as its chronic Clone-13 variant. This study examined the genetic trends in the vertical transmission of LCMV from mothers infected perinatally with Clone-13. Viral isolates obtained from the serum of congenital carrier offspring were partially sequenced to reveal residue 260 in the glycoprotein-encoding region of their S segment, the site of a major amino acid change differentiating the chronic and acute strains. It was found that the phenylalanine-to-leucine mutation associated with Clone-13 was present in 100% of the isolates, strongly indicating that the offspring of Clone-13 carriers contain exclusively the chronic variant. This research has broad implications for the epidemiology of the virus, and, given the predominance of Armstrong in the wild, suggests that there must be a biological cost associated with Clone-13 infection in non-carriers.
ContributorsFrear, Cody Christian (Author) / Blattman, Joseph (Thesis director) / Hogue, Brenda (Committee member) / Holechek, Susan (Committee member) / Barrett, The Honors College (Contributor) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Viral infections are a significant cause of disease in humans. While some viral diseases have been eliminated, many more continue to infect millions. Viral infections are challenging to treat because viruses use host cell machinery to replicate, so it is difficult to develop drugs that can target viruses. Normally, the host’s immune system is capable of destroying the virus, but during chronic infections it becomes exhausted and T cells lose their effector functions necessary for the clearance of the virus. IL-2 can help relieve this exhaustion, but causes toxicity to the body. In mice infected with chronic LCMV, IL-2 administration causes death due to pulmonary hemorrhage. CD4 deficient mice were infected with chronic LCMV and then dosed with IL-2 and survived, but mice that were deficient for CD8 T cells died, indicating that toxicity was mediated by CD8 T cells. CD8 T cells can kill infected host cells directly by producing perforin, or can produce cytokines like IFN-γ and TNF to further activate the immune system and mediate killing. Mice that were deficient in perforin died after IL-2 administration, as well as mice that were deficient in IFN-γ. Mice deficient in TNF, however, survived, indicating that TNF was mediating the toxicity in response to IL-2. There are two different receptors for TNF, p55 and p75. p55 is known as TNFR1 and has been implicated in apoptosis of virally infected cells. P75 is known as TNFR2 and is associated more with inflammation in response to infection. My hypothesis was that if TNFR2 was knocked out, infected mice would survive IL-2 dosing. When single knockouts of TNFR1 and 2 were used in an experiment however, it was found that either receptor is capable of mediating toxicity, as both experimental groups failed to survive. This is relevant to current IL-2 therapies because there is no way to eliminate a single receptor in order to reduce toxicity. Further studies exploring the anti-viral capabilities of IFN-γ are suggested.
ContributorsJarvis, Jordan Alisa (Author) / Blattman, Joseph (Thesis director) / Denzler, Karen (Committee member) / McAfee, Megan (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
Mizungo is a work of lyrical creative nonfiction with an interactive braided essay format that plays with place and time melding culture, experience, and memory. It weaves the threads of sexuality, loss, depression, privilege, and family between photographs. This develops the themes of otherness and identity while exploring the settings of Uganda, Tempe, and small-town Utah. The piece explores the identity of "mizungo," the name given by the locals to any white person who travels to Eastern Sub-Saharan Africa. In Uganda, a region known for both hospitality and homophobia, this identity overtakes the author's name and sense of self propeling the mizungo to near celebrity status simply because of skin color and the privilege it promises. For McGovern, this attention creates otherness and the isolation that forces self-reflection, which propels self-healing. "Mizungo" provides her a mask in the homophobic region, that not only protects, but promotes self-acceptance. It also forces her to face her grief over familial tragedies and contemplate the settings of depression, loss, and the makings of family around the world. The timeline of Mizungo flows nonlinearly, and does not stick to one setting. Along with her mental state, the narrative explores the world and the beginning and ending of the "mizungo" identity. The narrative drops the reader onto the streets of Kampala where McGovern is first branded as "mizungo" and ends with the exploration of a different meaning of this identity. In between these scenes, the narrative pulls from memories of childhood and summers spent in Utah up through nine years later in Tempe, a few months before the story was published, and a year after traveling to Uganda.
ContributorsMcgovern, Sophia Odonnell (Author) / Dombrowski, Rosemarie (Thesis director) / Hoyt, Heather (Committee member) / School of Politics and Global Studies (Contributor) / Department of English (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
Despite a continuously growing body of evidence that they are one of the major causes of pregnancy loss, preterm birth, pregnancy complications, and developmental abnormalities leading to high rates of morbidity and mortality, viruses are often overlooked and underestimated as teratogens. The Zika virus epidemic beginning in Brazil in 2015 brought teratogenic viruses into the spotlight for the public health community and popular media, and its infamy may bring about positive motivation and funding for novel treatments and vaccination strategies against it and a variety of other viruses that can lead to severe congenital disease. Lymphocytic choriomeningitis virus (LCMV) is famous in the biomedical community for its historic and continued utility in mouse models of the human immune system, but it is rarely a source of clinical concern in terms of its teratogenic risk to humans, despite its ability to cause consistently severe ocular and neurological abnormalities in cases of congenital infection. Possibilities for a safe and effective LCMV vaccine remain difficult, as the robust immune response typical to LCMV can be either efficiently protective or lethally pathological based on relatively small changes in the host type, viral strain, viral dose, method of infection/immunization, or molecular characteristics of synthetic vaccination. Introducing the immunologically unique state of pregnancy and fetal development to the mix adds complexity to the process. This thesis consists of a literature review of teratogenic viruses as a whole, of LCMV and its complications during pregnancy, of LCMV immunopathology, and of current understanding of vaccination against LCMV and against other teratogenic viruses, as well as a hypothetical experimental design intended to initially bridge the gaps between LCMV vaccinology and LCMV teratogenicity by bringing a vaccine study of LCMV into the context of viral challenge during pregnancy.
ContributorsHarris, Maryl (Author) / Blattman, Joseph (Thesis director) / Scotch, Matthew (Committee member) / Luna, Evelyn (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
The retinoid-X receptor (RXR) can form heterodimers with both the retinoic-acid
receptor (RAR) and vitamin D receptor (VDR). The RXR/RAR dimer is activated by ligand all
trans retinoic acid (ATRA), which culminates in gut-specific effector T cell migration. Similarly,
the VDR/RXR dimer binds 1,25(OH)2D3 to cause skin-specific effector T cell migration.
Targeted migration is a potent addition to current vaccines, as it would induce activated T cell
trafficking to appropriate areas of the immune system and ensure optimal stimulation (40).
ATRA, while in use clinically, is limited by toxicity and chemical instability. Rexinoids
are stable, synthetically developed ligands specific for the RXR. We have previously shown that
select rexinoids can enhance upregulation of gut tropic CCR9 receptors on effector T cells.
However, it is important to establish whether these cells can actually migrate, to show the
potential of rexinoids as vaccine adjuvants that can cause gut specific T cell migration.
Additionally, since the RXR is a major contributor to VDR-mediated transcription and
epidermotropism (15), it is worth investigating whether these compounds can also function as
adjuvants that promote migration by increasing expression of skin tropic CCR10 receptors on T
cells.
Prior experiments have demonstrated that select rexinoids can induce gut tropic migration
of CD8+ T cells in an in vitro assay and are comparable in effectiveness to ATRA (7). The effect
of rexinoids on CD4+ T cells is unknown however, so the aim of this project was to determine if
rexinoids can cause gut tropic migration in CD4+ T cells to a similar extent. A secondary aim
was to investigate whether varying concentrations in 1,25-Dihydroxyvitamin D3 can be linked to
increasing CCR10 upregulation on Jurkat CD4+ T cells, with the future aim to combine 1,25
Dihydroxyvitamin D3 with rexinoids.
These hypotheses were tested using murine splenocytes for the migration experiment, and
human Jurkat CD4+ T cells for the vitamin D experiment. Migration was assessed using a
Transwell chemotaxis assay. Our findings support the potential of rexinoids as compounds
capable of causing gut-tropic migration in murine CD4+ T cells in vitro, like ATRA. We did not
observe conclusive evidence that vitamin D3 causes upregulated CCR10 expression, but this
experiment must be repeated with a human primary T cell line.
receptor (RAR) and vitamin D receptor (VDR). The RXR/RAR dimer is activated by ligand all
trans retinoic acid (ATRA), which culminates in gut-specific effector T cell migration. Similarly,
the VDR/RXR dimer binds 1,25(OH)2D3 to cause skin-specific effector T cell migration.
Targeted migration is a potent addition to current vaccines, as it would induce activated T cell
trafficking to appropriate areas of the immune system and ensure optimal stimulation (40).
ATRA, while in use clinically, is limited by toxicity and chemical instability. Rexinoids
are stable, synthetically developed ligands specific for the RXR. We have previously shown that
select rexinoids can enhance upregulation of gut tropic CCR9 receptors on effector T cells.
However, it is important to establish whether these cells can actually migrate, to show the
potential of rexinoids as vaccine adjuvants that can cause gut specific T cell migration.
Additionally, since the RXR is a major contributor to VDR-mediated transcription and
epidermotropism (15), it is worth investigating whether these compounds can also function as
adjuvants that promote migration by increasing expression of skin tropic CCR10 receptors on T
cells.
Prior experiments have demonstrated that select rexinoids can induce gut tropic migration
of CD8+ T cells in an in vitro assay and are comparable in effectiveness to ATRA (7). The effect
of rexinoids on CD4+ T cells is unknown however, so the aim of this project was to determine if
rexinoids can cause gut tropic migration in CD4+ T cells to a similar extent. A secondary aim
was to investigate whether varying concentrations in 1,25-Dihydroxyvitamin D3 can be linked to
increasing CCR10 upregulation on Jurkat CD4+ T cells, with the future aim to combine 1,25
Dihydroxyvitamin D3 with rexinoids.
These hypotheses were tested using murine splenocytes for the migration experiment, and
human Jurkat CD4+ T cells for the vitamin D experiment. Migration was assessed using a
Transwell chemotaxis assay. Our findings support the potential of rexinoids as compounds
capable of causing gut-tropic migration in murine CD4+ T cells in vitro, like ATRA. We did not
observe conclusive evidence that vitamin D3 causes upregulated CCR10 expression, but this
experiment must be repeated with a human primary T cell line.
ContributorsDebray, Hannah Zara (Co-author) / Debray, Hannah (Co-author) / Blattman, Joseph (Thesis director) / Jurutka, Peter (Committee member) / Manhas, Kavita (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Poetry has served as my own personal emergency medicine throughout my entire life. Its ability to capture a moment in its entirety has allowed me to fully address my experiences so that I can use them as a source of personal growth rather than let them hinder me over time. For this same reason, I also believe poetry is the perfect medium to capture medical traumas. I based the poetry written in this collection on medical emergencies that I either personally experienced or witnessed firsthand shadowing the paramedics of the Anaheim Fire Department. Having the opportunity to witness medical emergencies from the perspective of first responders emphasized the uniqueness of professions in charge of handling emergency medical situations. One of the most important lessons learned from my experiences is that medical traumas are not rare, and an alarmingly high percentage of people will experience some sort of medical trauma in their lifetime. Therefore, it is incredibly important for people to be prepared to process the traumas and medical emergencies they will eventually encounter. The aim of Emergency Medicine is first and foremost to honor the individuals who are affected by medical emergencies and the first responders/emergency medical personnel who work tirelessly to preserve the lives of their patients. I also hope my poems serve as a reminder of the spontaneous nature of trauma and encourage readers to consider using poetry as a form of both healing and self-alignment. I am incredibly thankful for everyone who helped me complete this collection of poetry, however I am especially grateful for the direction given to me by Dr. Rosemarie Dombrowski.
ContributorsPoe, Campbell Riley (Author) / Dombrowski, Rosemarie (Thesis director) / Foote, Nicola (Committee member) / College of Health Solutions (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Inhibitor of growth factor 4 (ING4) is a tumor suppressor of which low expression has been associated with poor patient survival and aggressive tumor progression in breast cancer. ING4 is characterized as a transcription regulator of inflammatory genes. Among the ING4-regulated genes is CXCL10, a chemokine secreted by endothelial cells during normal inflammation response, which induces chemotactic migration of immune cells to the site. High expression of CXCL10 has been implicated in aggressive breast cancer, but the mechanism is not well understood. A potential signaling molecule downstream of Cxcl10 is Janus Kinase 2 (Jak2), a kinase activated in normal immune response. Deregulation of Jak2 is associated with metastasis, immune evasion, and tumor progression in breast cancer. Thus, we hypothesized that the Ing4/Cxcl10/Jak2 axis plays a key role in breast cancer progression. We first investigated whether Cxcl10 affected breast cancer cell migration. We also investigated whether Cxcl10-mediated migration is dependent on ING4 expression levels. We utilized genetically engineered MDAmb231 breast cancer cells with a CRISPR/Cas9 ING4-knockout construct or a viral ING4 overexpression construct. We performed Western blot analysis to confirm Ing4 expression. Cell migration was assessed using Boyden Chamber assay with or without exogenous Cxcl10 treatment. The results showed that in the presence of Cxcl10, ING4-deficient cells had a two-fold increase in migration as compared to the vector controls, suggesting Ing4 inhibits Cxcl10-induced migration. These findings support our hypothesis that ING4-deficient tumor cells have increased migration when Cxcl10 signaling is present in breast cancer. These results implicate Ing4 is a key regulator of a chemokine-induced tumor migration. Our future plan includes evaluation of Jak2 as an intermediate signaling molecule in Cxcl10/Ing4 pathway. Therapeutic implications of these findings are targeting Cxcl10 and/or Jak2 may be effective in treating ING4-deficient aggressive breast cancer.
ContributorsArnold, Emily (Author) / Kim, Suwon (Thesis director) / Blattman, Joseph (Thesis director) / Mason, Hugh (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Counternarratives is a print anthology of short fiction, nonfiction, and poetry that is characterized by refusal, resistance, and joy. The anthology contains works by writers from all over North America and is the product of a months-long process of collection and curation. The anthology is grounded in the experience of living in the desert southwest, and many of the works reflect that, but it also includes works that reflect different geographical experiences. What binds the works in the anthology together, ultimately, is the ways in which they refuse and resist dominant discourses that dehumanize for the sake of the global capitalist system and in which they joyfully embody alternative ways of existing. Some works take on the aforementioned system explicitly; others do so implicitly, but all of their truths speak to realities that it, through one mechanism or another, marginalizes and obscures. The anthology is published by Four Chambers Press.
ContributorsAnderson, Evan William (Author) / Dombrowski, Rosemarie (Thesis director) / Friedman, Jacob (Committee member) / School of International Letters and Cultures (Contributor) / Department of English (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05