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Washington University in St. Louis

Theses/Dissertations

2010

Cancer

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P38 Phoshporylates Rb On Ser567 By A Novel, Cell Cycle-Independent Mechanism That Triggers Rb-Hdm2 Interaction And Apoptosis, Rachel Delston Jan 2010

P38 Phoshporylates Rb On Ser567 By A Novel, Cell Cycle-Independent Mechanism That Triggers Rb-Hdm2 Interaction And Apoptosis, Rachel Delston

All Theses and Dissertations (ETDs)

The retinoblastoma protein: Rb) inhibits both cell division and apoptosis, but the mechanism by which Rb alternatively regulates these divergent outcomes remains poorly understood. Cyclin dependent kinases: Cdks) promote cell division by phosphorylating and reversibly inactivating Rb by a hierarchical series of phosphorylation events and sequential conformational changes. The stress-regulated mitogen activated protein kinase: MAPK) p38 also phosphorylates Rb, but it does so in a cell cycle-independent manner that is associated with apoptosis rather than with cell division. Here, we show that p38 phosphorylates Rb by a novel mechanism that is distinct from that of Cdks. p38 bypasses the cell …


Local And Systemic Consequences Of Reducing Notch Signaling In Skin Keratinocytes, Shadmehr Demehri Jan 2010

Local And Systemic Consequences Of Reducing Notch Signaling In Skin Keratinocytes, Shadmehr Demehri

All Theses and Dissertations (ETDs)

Notch is a transmembrane receptor that mediates short-range signaling between neighboring cells. Notch signaling has been implicated in various cellular and developmental processes essential in the life of metazoans. Specifically, Notch signaling plays a critical role in mammalian skin. Removal of Notch alleles in skin keratinocytes has been associated with an array of phenotypes with varying severity based on the identity and number of remaining Notch receptors. Phenotypes include carcinogenesis: in the case of Notch1 loss), transformation of hair follicles to epidermal cysts and neonatal lethality, the latter seen in the absence of all Notch signaling. Although these phenotypes were …


Breaking Bad News: Effect Of Physician Communication On Analog Patients' Response, Emily Porensky Jan 2010

Breaking Bad News: Effect Of Physician Communication On Analog Patients' Response, Emily Porensky

All Theses and Dissertations (ETDs)

Breaking bad news is a difficult, yet unavoidable part of healthcare for physicians and patients alike. Although expert opinion suggests that certain strategies for breaking bad news may be better than others, there is little methodologically rigorous research to support current guidelines. This study used an experimental paradigm to test two communication strategies, forecasting bad news and framing prognostic information, when giving people a life-limiting diagnosis of colon cancer. Videotapes depicted a physician disclosing a diagnosis of cancer and discussing prognosis. Participants: N = 128) were asked to imagine they were going to see a doctor for physical symptoms they …


High-Speed Photoacoustic Microscopy In Vivo, Liang Song Jan 2010

High-Speed Photoacoustic Microscopy In Vivo, Liang Song

All Theses and Dissertations (ETDs)

The overarching goal of this research is to develop a novel photoacoustic microscopy: PAM) technology capable of high-speed, high-resolution 3D imaging in vivo. PAM combines the advantages of optical absorption contrast and ultrasonic resolution for deep imaging beyond the quasi-ballistic regime. Its high sensitivity to optical absorption enables the imaging of important physiological parameters, such as hemoglobin concentration and oxygen saturation, which closely correlate with angiogenesis and hypermetabolism--two hallmarks of cancer. To translate PAM to the clinic, both high imaging speed and high spatial resolution are desired. With high spatial resolution, PAM can detect small structural and functional changes early; …


Role Of The Ajuba Lim Proteins In Epithelial Growth Regulation, Meghna Das Thakur Jan 2010

Role Of The Ajuba Lim Proteins In Epithelial Growth Regulation, Meghna Das Thakur

All Theses and Dissertations (ETDs)

The mammalian Ajuba LIM proteins: Ajuba, LIMD1, WTIP) are cytosolic adapter proteins recruited to nascent epithelial adherens junctions, where they are thought to contribute to junctional assembly and/or stability. They also shuttle into the nucleus acting as corepressors of the Snail family of transcriptional repressors, thereby contributing to epithelial mesenchymal transition. As such they have the potential to communicate cell adhesive events with nuclear responses to remodel epithelia. Determining their role(s) in vivo, however, has been challenging due to shared interacting proteins, overlapping tissue expression and functional redundancy in cells. Thus, we turned to the Drosophila model system where a …