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Articles 1 - 7 of 7
Full-Text Articles in Genetics and Genomics
Investigating The Roles Of Tap63 And Tap73 In Cutaneous Squamous Cell Carcinoma And Lung Adenocarcinoma, Andrew J. Davis
Investigating The Roles Of Tap63 And Tap73 In Cutaneous Squamous Cell Carcinoma And Lung Adenocarcinoma, Andrew J. Davis
Dissertations & Theses (Open Access)
TP63 and TP73 (which encode p63 and p73, respectively) are highly conserved transcription factors with important roles in development and tissue homeostasis. Similar to their homolog, p53, both p63 and p73 have been shown to mediate tumor suppression in multiple tissue types. Interestingly, however, both genes are expressed as multiple isoforms, which appear to have different and, in many cases, antagonistic functions. Through the use of isoform-specific null alleles of p63 and p73 our lab and others have shown that the full-length N-terminal isoforms of p63 and p73 (referred to as TAp63 and TAp73, respectively) exhibit distinct functions in development, …
Trim24 In Normal & Malignant Hematopoiesis, Justin Shaw
Trim24 In Normal & Malignant Hematopoiesis, Justin Shaw
Dissertations & Theses (Open Access)
Treatment for acute myeloid leukemia (AML) has changed little in the past four decades. For the majority of AML patients, current treatment options include chemotherapy and allogeneic stem cell transplants, which also involves high-dose chemotherapy or radiation treatment. These options have little success in the long-run, as only an estimated 26% of patients survive five years post-diagnosis. In efforts to address this low survival rate, interest has increased for targeting epigenetic pathways in AML. This focus stems from the discovery that AML is frequently driven by blockades on hematopoietic stem cell differentiation, which involves a series of coordinated epigenetic changes. …
Investigating Invasion In Ductal Carcinoma In Situ With Topographical Single Cell Genome Sequencing, Anna Casasent, Anna Casasent
Investigating Invasion In Ductal Carcinoma In Situ With Topographical Single Cell Genome Sequencing, Anna Casasent, Anna Casasent
Dissertations & Theses (Open Access)
Synchronous Ductal Carcinoma in situ (DCIS-IDC) is an early stage breast cancer invasion in which it is possible to delineate genomic evolution during invasion because of the presence of both in situ and invasive regions within the same sample. While laser capture microdissection studies of DCIS-IDC examined the relationship between the paired in situ (DCIS) and invasive (IDC) regions, these studies were either confounded by bulk tissue or limited to a small set of genes or markers. To overcome these challenges, we developed Topographic Single Cell Sequencing (TSCS), which combines laser-catapulting with single cell DNA sequencing to measure genomic copy …
Phosphorylation Impairs Dicer1 Function To Accelerate Aging And Tumorigenesis In Vivo, Neeraj Aryal
Phosphorylation Impairs Dicer1 Function To Accelerate Aging And Tumorigenesis In Vivo, Neeraj Aryal
Dissertations & Theses (Open Access)
Altered DICER1 protein levels are associated with developmental disorders, infertility, macular degenerative blindness, aging, and cancer in humans. Recently, post-translational regulation of Dicer1 via phosphorylation has been described in C. elegans. Oscillation of Dicer1 phosphorylation to regulate its activity is essential for germ cell development and embryogenesis in worms. These observations led us to posit that Dicer1 protein levels and activity are under tight regulation for normal mammalian homeostasis. To test whether phosphorylation of Dicer1 regulates its activity in mammals, I generated phospho-mimetic knock-in mouse models by replacing Serines 1712 and 1836 with Aspartic acids individually or together (dual …
Trim24 As An Oncogene In The Mammary Gland, Aundrietta Duncan
Trim24 As An Oncogene In The Mammary Gland, Aundrietta Duncan
Dissertations & Theses (Open Access)
Despite the many advances made in breast cancer research and treatments, breast cancer remains one of the deadliest diseases plaguing women worldwide. While many findings on genetic mutations and their role in predisposing people to breast cancer have been uncovered, we are just beginning to understand the extent to which epigenetic regulators promote tumorigenic phenotypes, metastasis, and chemotherapeutic resistance. Moreover, new experimental tools offer the ability to address questions we were previously unable to assess. My project takes advantage of a new mouse model to understand the role of a proto-oncogenic, transcriptional co-regulator, TRIM24, in mammary gland development and disease. …
Identification And Utility Of Dna In Exosomes, Paul Kurywchak
Identification And Utility Of Dna In Exosomes, Paul Kurywchak
Dissertations & Theses (Open Access)
Cancer-associated mortality has been declining for two decades but remains a significant public health problem, especially when patients initially present with advanced disease. Early detection methods have improved survival rates but remain unavailable for a majority of cancers due to a lack of sensitive biomarkers or numerous limitations associated with current diagnosis strategies. Approaches to develop “liquid biopsies” by detecting tumor cells or DNA in the blood have led to several breakthroughs and create the potential for non-invasive, routine assessment of diseases status. However, these biomarkers are rare and currently difficult to isolate, especially in the early stages of disease. …
The Regulation Of Dna Methylation In Mammalian Development And Cancer, Nicolas Veland
The Regulation Of Dna Methylation In Mammalian Development And Cancer, Nicolas Veland
Dissertations & Theses (Open Access)
DNA methylation is an essential epigenetic modification in mammals, as it plays important regulatory roles in multiple biological processes, such as gene transcription, maintenance of chromosomal structure and genomic stability, genomic imprinting, retrotransposon silencing, and X-chromosome inactivation. Dysregulation of DNA methylation is associated with various human diseases. For example, cancer cells usually show global hypomethylation and regional hypermenthylation, which have been implicated in genomic instability and tumor suppressor silencing, respectively. Although great progress has been made in elucidating the biological functions of DNA methylation over the last several decades, how DNA methylation patterns and levels are regulated and dysregulated is …