Theses and dissertations

This collection includes both ASU Theses and Dissertations, submitted by graduate students, and the Barrett, Honors College theses submitted by undergraduate students. 

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Tumor-induced upregulation of A2AR on effector CD8 T cells promotes tumor growth in melanoma

Description
Purinergic receptors sense extracellular nucleotide DAMPs such as ATP and adenosine, which are expressed in high concentrations in the tumor microenvironment (TME). A2AR, an adenosine receptor that is expressed on both T cells and tumor cells, promotes immunosuppression. However, the impact of the TME on changes in purinergic receptor expression…

Purinergic receptors sense extracellular nucleotide DAMPs such as ATP and adenosine, which are expressed in high concentrations in the tumor microenvironment (TME). A2AR, an adenosine receptor that is expressed on both T cells and tumor cells, promotes immunosuppression. However, the impact of the TME on changes in purinergic receptor expression on CD8 T cells, as well as the overall dynamic between A2AR expression and tumor control, have not been clearly elucidated. Using in vitro co-culture experiments and in vivo murine tumor models, we found that A2AR is significantly upregulated on effector, tumor-infiltrating CD8 T cells. This upregulation was independent of the hypoxia, which we identified via inhibition of HIF1A. We found that this upregulation was partially dependent on CD8 T cell-tumor contact, but independent of cognate antigen recognition, by using transwell co-cultures, as well as combinations of different transgenic lines of CD8 T cells and tumor cells. We confirmed this observation in vivo using transfer of activated OTI cells into B16.OVA-bearing mice. Ultimately, we observed that the upregulation depended on inhibitory receptors such as Tim3 via the antibody blockade of Tim3. Using CRISPR/Cas9-mediated knockout of A2AR on activated CD8 T cells, we found that tumor-bearing mice receiving A2AR knockout CD8 T cells had increased tumor control. Taken together, these results suggest that inhibitory receptor-dependent, TCR-independent signals in the TME promotes upregulation of A2AR on CD8 T cells, leading to impairment of CD8 T cell-mediated tumor control.
ContributorsZhou, Maggie (Author) / Borges da Silva, Henrique (Thesis director) / Borges Florsheim, Esther (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / Economics Program in CLAS (Contributor)
Created2022-12
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Genetic and Environmental Contributions to the Relation Between Parenting and Child Psychopathology

Description

Prior research has established a relation between parenting behaviors and symptoms of child psychopathology, and this association may be influenced by both genetic and environmental factors. Gene-environment correlation, or the influence of a child’s genes on the environment they receive, represents one possible mechanism through which genes and environment combine…

Prior research has established a relation between parenting behaviors and symptoms of child psychopathology, and this association may be influenced by both genetic and environmental factors. Gene-environment correlation, or the influence of a child’s genes on the environment they receive, represents one possible mechanism through which genes and environment combine to influence child outcomes. This study examined evocative gene-environment correlation in the relation between parenting and symptoms of child psychopathology in a sample of 676 twins (51.5% female, 58.5% Caucasian, 23.7% Hispanic/Latinx, primarily middle class, MAge=8.43, SD=.62) recruited from Arizona birth records. Using univariate ACE twin biometric models, genetic influences were found to moderately contribute to internalizing symptoms (A=.47, C=.25, E=.28), while externalizing (A=.86, E=.14) and ADHD (A=.84, E=.16) symptoms were found to be highly heritable. The genetic influences for positive (C=.54, E=.46) and negative (C=.44, E=.56) parenting were smaller and found to be nonsignificant. The correlations between parenting and types of psychopathology were examined and bivariate Cholesky decompositions were conducted for statistically significant correlations. Negative parenting was moderately positively correlated with externalizing and ADHD symptoms; the relation between externalizing symptoms and negative parenting was found to be due to shared genetics, whereas the relation between negative parenting and ADHD symptoms was due to the shared environment. The mixed results regarding the role of gene environment correlation in relations between parenting and child psychopathology indicate that further research on the mechanisms of this relation is needed.
ContributorsCarrizosa, Mya Grace (Author) / Lemery-Chalfant, Kathryn (Thesis director) / Corbin, William (Committee member) / Davis, Mary (Committee member) / Oro, Veronica (Committee member) / Department of Information Systems (Contributor) / Economics Program in CLAS (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05