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Analysis Of Band 4.1b In Integrin-Mediated Cell Adhesion And Signaling, Youngsin Jung
Analysis Of Band 4.1b In Integrin-Mediated Cell Adhesion And Signaling, Youngsin Jung
Dissertations & Theses (Open Access)
Band 4.1B is a cytoskeletal adaptor protein that regulates various cellular behavior; however, the mechanisms by which Band 4.1B contributes to intracellular signaling are unclear. This project addresses in vivo and in vitro functions for Band 4.1B in integrin-mediated cell adhesion and signaling. Band 4.1B has been shown to bind to β8 integrin, although cooperative functions of these two proteins have not been determined. Here, functional links between β8 integrin and Band 4.1B were investigated using gene knockout strategies. Ablation of β8 integrin and Band 4.1B genes resulted in impaired cardiac morphogenesis, leading to embryonic lethality by E11.5. These embryos …
Investigating The Effects Of Silencing Epha2 In Metastatic Breast Cancer Cells, Stephanie Erzinger
Investigating The Effects Of Silencing Epha2 In Metastatic Breast Cancer Cells, Stephanie Erzinger
Dissertations & Theses (Open Access)
EphA2, also known as ECK (epithelial cell kinase), is a transmembrane receptor tyrosine kinase that is commonly over-expressed in cancers such as those of the prostate, colon, lung, and breast. For breast cancers, EphA2 overexpression is most prominent in the ER-negative subtype, and is associated with a higher rate of lung metastasis. Studies conducted to demonstrate the role of EphA2 in a non-cancerous environment have shown that it is very important in developmental processes, but not in normal adult tissues. These results make EphA2 a prospective therapeutic target since new therapies are needed for the more aggressive ER-negative breast cancers. …
The Role And Mechanism Of The Homeobox Gene Dlx4 In Transforming Growth Factor-B Resistance In Cancer, Bon Q. Trinh
The Role And Mechanism Of The Homeobox Gene Dlx4 In Transforming Growth Factor-B Resistance In Cancer, Bon Q. Trinh
Dissertations & Theses (Open Access)
Transforming growth factor-b (TGF-b) is a cytokine that plays essential roles in regulating embryonic development and tissue homeostasis. In normal cells, TGF-b exerts an anti-proliferative effect. TGF-b inhibits cell growth by controlling a cytostatic program that includes activation of the cyclin-dependent kinase inhibitors p15Ink4B and p21WAF1/Cip1 and repression of c-myc. In contrast to normal cells, many tumors are resistant to the anti-proliferative effect of TGF-b. In several types of tumors, particularly those of gastrointestinal origin, resistance to the anti-proliferative effect of TGF-b has been attributed to TGF-b receptor or Smad mutations. However, these mutations are absent from many …
Prevalence Of Premature Ovarian Failure In Women With Tuberous Sclerosis, Emily Gabitzsch
Prevalence Of Premature Ovarian Failure In Women With Tuberous Sclerosis, Emily Gabitzsch
Dissertations & Theses (Open Access)
Tuberous Sclerosis Complex (TSC) is an autosomal dominant tumor suppressor disorder characterized by hamartomas, or benign growths, in various organ systems. Inactivating mutations in either the TSC1 or the TSC2 gene cause most cases of TSC. Recently, the use of ovarian specific conditional knock-out mouse models has demonstrated a crucial role of the TSC genes in ovarian function. Mice with complete deletion of Tsc1 or Tsc2 showed accelerated ovarian follicle activation and subsequent premature follicular depletion, consistent with the human condition premature ovarian failure (POF). POF is defined in women as the cessation of menses before the age of 40 …
Role Of Synapsin In Long-Term Synaptic Facilitation In Aplysia, Anne Hart
Role Of Synapsin In Long-Term Synaptic Facilitation In Aplysia, Anne Hart
Dissertations & Theses (Open Access)
Enhanced expression of the presynaptic protein synapsin has been correlated with certain forms of long-term plasticity and learning and memory. However, the regulation and requirement for enhanced synapsin expression in long-term memory remains unknown. In the present study the technical advantages of the marine mollusc Aplysia were exploited in order to address this issue. In Aplysia, learning-induced enhancement in synaptic strength is modulated by serotonin (5-HT) and treatment with 5-HT in vitro of the sensorimotor synapse induces long-term facilitation (LTF) of synaptic transmission, which lasts for days, as well as the formation of new connections between the sensory and …
Immune Modulation Of The Mycobacterium Tuberculosis Granulomatous Response, Kerry J. Welsh
Immune Modulation Of The Mycobacterium Tuberculosis Granulomatous Response, Kerry J. Welsh
Dissertations & Theses (Open Access)
Tuberculosis (TB) remains a major public health burden. The immunocompetant host responds to Mycobacterium tuberculosis (MTB) infection by the formation of granulomas, which initially prevent uncontrolled bacterial proliferation and dissemination. However, increasing evidence suggests that granuloma formation promotes persistence of the organism by physically separating infected cells from effector lymphocytes and by inducing a state of non-replicating persistence in the bacilli, making them resistant to the action of antibiotics. Additionally, immune-mediated tissue destruction likely facilitates disease transmission. The granulomatous response is in part due to mycobacterial glycolipid antigens. Therefore, studies were first undertaken to determine the innate mechanisms of mycobacterial …
Physician Perceptions Of Risk Regarding Mood Disorders And Pharmacological Management During Pregnancy: What Is Current Practice?, Laura G. Hendon
Physician Perceptions Of Risk Regarding Mood Disorders And Pharmacological Management During Pregnancy: What Is Current Practice?, Laura G. Hendon
Dissertations & Theses (Open Access)
Mood disorders are the most common form of mental illness and one of the leading causes of morbidity worldwide. Major depressive disorder and bipolar disorder have a lifetime prevalence of 16.2% and 4.4%, respectively. Women comprise a substantial proportion of this population, and an estimated 500,000 pregnancies each year involve women with a psychiatric condition. Management with psychotropic medications is considered standard of care for most patients with mood disorders. However, many of these medications are known human teratogens. Because pregnant women with mood disorders face a high risk of relapse if unmanaged, the obstetrician faces a unique challenge in …
A Novel Function For Aurora B Kinase In The Regulation Of P53 By Phosphorylation, Chris P. Gully
A Novel Function For Aurora B Kinase In The Regulation Of P53 By Phosphorylation, Chris P. Gully
Dissertations & Theses (Open Access)
The mitotic kinase Aurora B plays a pivotal role in mitosis and cytokinesis and governs the spindle assembly checkpoint which ensures correct chromosome segregation and normal progression through mitosis. Aurora B is overexpressed in breast and other cancers and may be an important molecular target for chemotherapy. Tumor suppressor p53 is the guardian of the genome and an important negative regulator of the cell cycle. Previously, it was unknown whether Aurora B and p53 had mutual regulation during the cell cycle. A small molecule specific inhibitor of Aurora B, AZD1152, gave us an indication that Aurora B negatively impacted p53 …