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The Human Arf Tumor Suppressor Regulates Drosha Nucleolar Localization And Rrna Processing Activity, Sree Chandana Sridhar Yaddanapudi

Arts & Sciences Electronic Theses and Dissertations

Ribosomes are vital to the survival of a cell, as they are directly responsible for the synthesis of proteins, which perform critical cellular functions. As such, majority of the energy reserves in a proliferating cell are expended towards synthesis of ribosomes. Cancer cells, with their enhanced proliferation rates, tend to upregulate ribosome biogenesis in order to meet the demand for increased protein synthesis necessary to sustain rapid proliferation. Many of the oncogenes and tumor suppressors known to be deregulated in cancers are capable of positively and negatively regulating ribosome biogenesis, respectively. The ARF tumor suppressor strongly suppresses ribosome biogenesis, particularly …

Survival Analysis In A Clinical Setting, Yunzhao Liu

Arts & Sciences Electronic Theses and Dissertations

With the fast paced advancement of modern medicine, cancer treatments have improved greatly over the past few decades; however, the overall survival rate has not improved for head neck squamous cell carcinoma (HNSCC). Traditionally, the general affected population of HNSCC was male over 50-60 years of age, whom have had history of alcohol and tobacco use. Conversely, in the recent decades, HNSCC has exhibited significant rise in younger patients, largely due to the increase in human papillomavirus (HPV) infection among young adults.

Generally, HPV as the most prevalent sexually transmitted disease, consisted of strains that do not cause harm to …

The P38mapk-Mk2-Hsp27 Axis Regulates The Mrna Stability Of The Pro-Tumorigenic Senescence-Associated Secretory Phenotype, Hayley Reynolds Moore

Arts & Sciences Electronic Theses and Dissertations

Protecting the genome is a vital aspect of safeguarding organismal health. Inability to efficiently and effectively replicate the genome or repair damage the genome may encounter can lead to mutational accumulation or senescence, both of which are drivers of multiple diseases including cancer. Understanding the mechanisms by which the genome is maintained, as well as the consequences of repeated rounds of replication or exposure to DNA damaging agents, will allow for greater understanding of the diseases they promote as well as development of targeted therapies aimed at mitigating the detrimental effects of genomic insult. The first section of my work …

The Role Of Dnmt3a In Acute Myeloid Leukemia Pathogenesis, Christopher Browning Cole

Arts & Sciences Electronic Theses and Dissertations

Loss of function mutations in the DNA methyltransferase DNMT3A are highly recurrent in acute myeloid leukemia (AML). DNMT3A and the highly homologous gene DNMT3B encode the two methyltransferases that are primarily responsible for mediating de novo methylation of specific DNA sequences during cellular differentiation. DNMT3A mutations are mutually exclusive of several translocations that create oncogenic fusion genes (PML-RARA, RUNX1-RUNX1T1, CBFB-MYH11, and MLL-X), suggesting that these fusions may require functional DNMT3A to initiate leukemogenesis. Using bone marrow cells from a constitutive Dnmt3a null mouse, we show that loss of Dnmt3a caused a striking loss of DNA methylation throughout the genome of …