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dc.contributor.advisorWhitty, Adrianen_US
dc.contributor.authorChow, Jennifer Marieen_US
dc.date.accessioned2018-03-23T15:00:39Z
dc.date.available2018-03-23T15:00:39Z
dc.date.issued2018
dc.identifier.urihttps://hdl.handle.net/2144/27853
dc.description.abstractMost existing studies of receptor signaling are qualitative, which can lead scientists to misinterpret or overlook key information about the extent and timing of key events. To overcome these shortcomings, we have applied quantitative approaches to characterize receptor activation and signaling events. Most signaling studies focus on events occurring at a particular level in the system (e.g., on the membrane, at the level of phosphorylation of intracellular signaling molecules, or at the level of transcription). Instead, we are interested in taking a longitudinal view of signaling by achieving a quantitative understanding of a single signaling pathway from initial stimulation of the receptor by its growth factor (GF) ligand, through to gene expression, and functional cellular responses. As a model system for our studies, we used the growth factor receptor tyrosine kinase, REarranged during Transfection (RET), which requires a ligand and a glycosylphosphatidylinositol-anchored co-receptor for activation. RET mediates the response of cells to members of the glial cell-line derived neurotrophic factor (GDNF) family of neurotrophins, which are important in the development and maintenance of a subset of neuronal cells as well as in other cell types and tissues. We have characterized the molecular mechanisms of RET activation and signaling by pursuing the following four aims: 1) We developed a sensitive and robust luciferase reporter gene assay for RET signaling. 2) We characterized the dynamic relationship between receptor activation and downstream signaling events, including gene transcription and translation of three target genes. 3) We used the reporter gene assay, and other detection approaches, to test and quantify crosstalk between RET and other GF receptors. 4) We developed a FRET reporter system to enable monitoring of the assembly of the activated RET receptor complex on cells, as a means to distinguish between ligand-induced oligomerization and pre-associated oligomer mechanisms. Through these four aims, we have established new methods to quantitatively elucidate mechanisms of GF receptor activation, new insights into how signals are propagated from the receptor to the nucleus and into a functional response, and have established crosstalk between RET and other GF receptor pathways.en_US
dc.language.isoen_US
dc.subjectBiochemistryen_US
dc.subjectCell signalingen_US
dc.subjectGrowth factor receptoren_US
dc.subjectmRNA dynamicsen_US
dc.subjectProtein dynamicsen_US
dc.subjectSignaling dynamicsen_US
dc.subjectSignaling kineticsen_US
dc.titleQuantitative analysis of RET signaling dynamics and crosstalken_US
dc.typeThesis/Dissertationen_US
dc.date.updated2018-03-18T01:24:58Z
etd.degree.nameDoctor of Philosophyen_US
etd.degree.leveldoctoralen_US
etd.degree.disciplineChemistryen_US
etd.degree.grantorBoston Universityen_US


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