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Novel Insights Into The Role Of The Smoothened Cysteine Rich Domain In Hedgehog Signalling, Rajashree Rana Dec 2014

Novel Insights Into The Role Of The Smoothened Cysteine Rich Domain In Hedgehog Signalling, Rajashree Rana

Theses and Dissertations (ETD)

The Hedgehog (Hh) signal transduction pathway functions as one of the key developmental pathways and deranged Hh signalling is associated with numerous cancer and tumor conditions. The Smoothened (Smo) G protein coupled receptor (GPCR) functions as the signal transducer of the Hh pathway and is the most attractive drug target of the pathway. The structure of the Smo receptor includes seven membrane spanning domains, extracellular and intracellular loops connecting the membranous domains and the extracellular cysteine rich domain (CRD). The extracellular CRD of the Smo receptor is homologous to the Frizzled (FzD) CRD. The FzD CRD interacts with the physiological …


Mrp4-Dependent Regulation Of Fibroblast Migration, Chandrima Sinha Dec 2014

Mrp4-Dependent Regulation Of Fibroblast Migration, Chandrima Sinha

Theses and Dissertations (ETD)

Roles of cyclic nucleotides and cyclic nucleotide-dependent signaling molecules in regulating several signaling pathways including cell migration have long been known. However, the new and revolutionary concept is that it is not just the absence or presence of cyclic nucleotides, but a highly coordinated balance between these molecules regulates cell migration. Multi-drug resistance protein 4 (MRP4), is a member of the large family of ATP binding cassette (ABC) transporter proteins, that localizes to the plasma membrane and functions as a nucleotide efflux transporter and thus plays a pivotal role in the regulation of intracellular cyclic nucleotide dynamics. In our study …


Functional And Genetic Analysis Of Choroid Plexus Development In Zebrafish, Hannah Elizabeth Henson Aug 2014

Functional And Genetic Analysis Of Choroid Plexus Development In Zebrafish, Hannah Elizabeth Henson

Theses and Dissertations (ETD)

The choroid plexus (CP) is an epithelial based structure localized within the brain ventricles and functions as the blood-cerebrospinal fluid barrier (BCSFB). Under normal conditions, the CP is responsible for generating the cerebrospinal fluid (CSF) and regulating its components. Abnormal CP function has been associated with neurodegenerative diseases, tumor formation in CP epithelia (CPe), and hydrocephalus. Despite the significant role of the CP in these disorders, little research has been done to characterize its functional properties and genetically dissect the pathways involved in normal CP development and disease. For this study, we have utilized zebrafish, (Danio rerio), as a model …


The Mi-2 Homolog Mit1 Actively Positions Nucleosomes Within Heterochromatin To Suppress Transcription, Kevin M. Creamer May 2014

The Mi-2 Homolog Mit1 Actively Positions Nucleosomes Within Heterochromatin To Suppress Transcription, Kevin M. Creamer

Theses and Dissertations (ETD)

Eukaryotic DNA is packaged into the nucleus in complex with proteins that regulate access and utilization of the genetic material. These DNA and protein complexes form a dynamic structure known as chromatin. Nucleosomes are the repeating unit of chromatin, and consist of DNA wrapped around an octamer of histone proteins. Nucleosomes can then be modified and spatially arranged to facilitate processes such as transcription, DNA replication, and repair. A special transcriptionally repressive chromatin structure assembles onto gene-poor, repetitive regions of the genome known as constitutive heterochromatin. Mit1 is the putative chromatin remodeling subunit of the fission yeast Snf2/HDAC repressor complex …


Molecular Characterization Of Glioblastoma Cancer Stem Cells, Jo Meagan Garner May 2014

Molecular Characterization Of Glioblastoma Cancer Stem Cells, Jo Meagan Garner

Theses and Dissertations (ETD)

Malignant gliomas are locally aggressive, highly vascular tumors that have an overall survival time less than 14 months, and current therapies provide little improvement in the disease course and outcome. While glioblastoma multiforme (GBM) patients present uniform histological phenotypes, the molecular determinants of the disease vary considerably between individual cases resulting in complicated prognosis. The heterogeneity, aggressiveness and rapid tumor relapse of GBM is believed to be sustained by cancer stem-like cell populations that are able to initiate and maintain tumors. Although CSCs represent only a small fraction of cells within a tumor, their high tumor-initiating capacity and therapeutic resistance …