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Dna Polymerase Ε: Replication Error Prevention And Consequences Of A Cancer-Associated Mutation, Chelsea R. Bulock
Dna Polymerase Ε: Replication Error Prevention And Consequences Of A Cancer-Associated Mutation, Chelsea R. Bulock
Theses & Dissertations
Genome integrity is necessary to prevent mutations and disease. During eukaryotic DNA replication, DNA polymerases ε (Polε) and δ (Polδ) synthesize the leading and lagging strand, respectively. Polε and Polδ also have exonuclease activity that acts in series with post-replicative mismatch repair (MMR) to remove replication errors. Defects in proofreading and MMR lead to an increase in mutations and cause cancer in humans. This dissertation focuses on several unresolved issues involving the relationship between Polε and Polδ in replication error avoidance. First, despite an abundance of data supporting the one-strand-one-polymerase replication fork model, defects in the fidelity of Polε have …
Genomic And Transcriptomic Alterations In Metabolic Regulators And Implications For Anti-Tumoral Immune Response, Ryan J. King
Genomic And Transcriptomic Alterations In Metabolic Regulators And Implications For Anti-Tumoral Immune Response, Ryan J. King
Theses & Dissertations
Metabolic and immune alterations are ubiquitous hallmarks of cancer that are established during the foundational mutations and are further selected upon to generate highly aggressive tumors. Recent evidence suggests that cancer cells employ an altered metabolism to induce immune evasion. To further discover the relationship between metabolism and immunity in cancer, this thesis aimed to discover potential candidates of interest by first examining the mucin family for differences, as they exert a wide range of activities in cancer, including altered metabolism and immune alterations. Unique differences lead to further profiling in pancreatic and esophageal cancer. In pancreatic cancer, CD73 was …
From Development To Therapy: A Panoramic Approach To Further Our Understanding Of Cancer, Brittany Poelaert
From Development To Therapy: A Panoramic Approach To Further Our Understanding Of Cancer, Brittany Poelaert
Theses & Dissertations
Solid tumors, such as pancreatic cancer, often result in dismally low survival outcomes for patients due to insufficient understanding of disease development and progression. Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and although oncogenic drivers (such as KRAS mutation or loss of tumor suppressor p53) and stages of disease development have been studied, further understanding of pancreatic cancer development is greatly needed. Studies from our laboratory have identified novel and varied functions of amyloid precursor-like protein 2 (APLP2) in the development and progression of pancreatic cancer. These functions include promoting cancer cell migration, …
The Role Of The Cxcr3 Signaling Axes In Pancreatic Ductal Adenocarcinoma, Andrew C. Cannon
The Role Of The Cxcr3 Signaling Axes In Pancreatic Ductal Adenocarcinoma, Andrew C. Cannon
Theses & Dissertations
Numerous cytokines promote pancreatic ductal adenocarcinoma (PDAC) progression and suppress anti-tumor immune response leading to poor prognosis in PDAC patients. Despite this, many cytokines, have not been investigated in PDAC. Bioinformatic analyses of PDAC microarray and RNA-Seq datasets were used to identify cytokines overexpressed in PDAC, confirm the expression of cognate receptors, determine the association of cytokines with patient survival and define key underlying molecular associations. Bioinformatic findings were validated using immunohistochemical (IHC) staining, comparative cytokine qPCR-array in KrasLSL-G12D:TP53LSL-R172H:Pdx1-Cre (KPC) and KrasLSL-G12D:Pdx1-Cre (KC) PDAC models and multicolor immunofluorescence staining. Tail-vein injections of PDAC cells …