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Targeting Bet Proteins Downregulates Mir-33a To Promote Synergy With Pim Inhibitors In Cmml, Christopher T. Letson
Targeting Bet Proteins Downregulates Mir-33a To Promote Synergy With Pim Inhibitors In Cmml, Christopher T. Letson
USF Tampa Graduate Theses and Dissertations
Chronic Myelomonocytic Leukemia (CMML) is a rare myeloid malignancy with a dismal prognosis and no therapeutic options which are capable of altering the natural course of the disease. There remains a significant need for novel therapies that are able to meaningfully improve patient outcomes. In this study we explore the effectiveness of Bromodomain and Extra-Terminal domain protein inhibitor (BETi) combinations in CMML. Preclinical studies in myeloid neoplasms have demonstrated efficacy of BETi. However, BETi demonstrate poor single agent activity in clinical trials. Several studies suggest that combinations with other anti-cancer inhibitors may enhance the efficacy of BETi. To nominate BETi …
Thermodynamic Frustration Of Tad2 And Prr Contribute To Autoinhibition Of P53, Emily Gregory
Thermodynamic Frustration Of Tad2 And Prr Contribute To Autoinhibition Of P53, Emily Gregory
USF Tampa Graduate Theses and Dissertations
The intrinsically disordered transcription factor and tumor suppressor p53 binds to promoter response element DNA upon cellular stress and activates genes associated with cell cycle arrest, senescence, and apoptosis. Disruption of sequence specific binding to target gene promoters is heavily implicated in human health, where a majority of cancers contain mutations localized to the DNA binding domain (DBD) of p53. p53 DNA binding is regulated by posttranslational modifications, associations with cellular factors, and by an autoinhibitory intramolecular interaction. The autoinhibitory intramolecular interaction occurs when the disordered N-terminal transactivation domain (TAD) interacts with the ordered DBD. Previous work in the Daughdrill …
Withaferin A And Immune Checkpoint Blocker Therapy For The Treatment Of Non-Small Cell Lung Cancer, Roukiah Khalil
Withaferin A And Immune Checkpoint Blocker Therapy For The Treatment Of Non-Small Cell Lung Cancer, Roukiah Khalil
USF Tampa Graduate Theses and Dissertations
Lung cancer is the first cause of cancer-related deaths in both men and women with an overall five-year survival rate of 28%. Although immune checkpoint blockers (ICBs) are currently FDA-approved for the treatment of non-small cell lung cancer (NSCLC), only 17-20% of patients achieve durable responses by the induction of immunologic memory. The lack of response in most patients can be attributed to the tumor-intrinsic or tumor-extrinsic immune resistance mechanisms. A biomarker of importance is the Programmed Death Ligand-1 (PD-L1), as higher PD-L1 expression is usually associated with a better response to ICBs. Although studies have attempted to combine ICBs …
Exploring Strain Variation And Bacteriophage Predation In The Gut Microbiome Of Ciona Robusta, Celine Grace F. Atkinson
Exploring Strain Variation And Bacteriophage Predation In The Gut Microbiome Of Ciona Robusta, Celine Grace F. Atkinson
USF Tampa Graduate Theses and Dissertations
Current microbiome studies have shown that the maintenance of homeostasis betweenmicrobial populations (e.g. bacteria, viruses) and the host immune system (e.g. innate immune molecules) is necessary for balancing health and disease outcomes within the host. These studies most often utilize vertebrate models; however, research in this field can benefit from diverse model systems that facilitate our ability to conduct experiments to identify phylogenically conserved rules influencing homeostasis in the gut of animals. The Dishaw has developed the use of a filter-feeding marine invertebrate chordate, Ciona robusta, to model such fundamental interactions[1]–[6]. While most biological diversity and functional contribution within microbiomes …
A Novel Role For Enos In Regulating Lymphatic Valve Development During Embryogenesis, Drishya Iyer
A Novel Role For Enos In Regulating Lymphatic Valve Development During Embryogenesis, Drishya Iyer
USF Tampa Graduate Theses and Dissertations
Lymphedema is a disease that occurs when lymph flow is impaired, resulting in tissue swelling, fibrosis, chronic inflammation and recurrent secondary infections. Lymphatic valves play a critical role in maintaining unidirectional lymph flow and evidence for valve defects have been reported in lymphedema patients. The lack of drugs that can correct lymphatic valve defects warrants a better understanding of the molecular regulators of lymphatic valve development and maintenance. Lymphatic valves first develop during embryogenesis in response to mechanotransduction signaling pathways triggered by oscillatory lymph flow. Since eNOS (gene name: Nos3) is a well characterized mechanotransduction signaling molecule in blood vessels, …