Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
Results
Showing 1 to 20 of 26 for “"the Hippo pathway"”.
-
Genetic Analysis of The Hippo Pathway In Mouse Liver
<p>Cancer therapy and tumor treatment remain unsolved puzzles. Genetic screening for tumor suppressor genes in <em>Drosophila</em> revealed the Hippo-signaling pathway as a kinase cascade consisting of five core components. Disrupting the pathway by deleting the main component genes breaks the …
-
Cell Polarity Regulates Organ Growth Through The Hippo Pathway
… apical-basal polarity, including overexpressing the apical determinant Crumbs, can lead to uncontrolled tissue growth. Cells mutant for the basolateral determinant <em>scribble </em>overproliferate and can form neoplastic tumors. Interestingly, <em>scribble </em>mutant clones that arise in …
-
Genetic modeling of the Hippo pathway in hematopoietic stem cells
Hematopoiesis is the process of blood formation from a limited pool of hematopoietic stem cells (HSCs). These rare stem cells can both self-renew to maintain the HSC pool, and differentiate to continuously replenish lost blood cells. The mechanisms of HSC regulation are not fully known. The aim of …
-
Negative Regulation of the Hippo Pathway by the Ajuba LIM Proteins
<p>The highly conserved Hippo kinase cascade is critical for both regulation of organ size in development and tumor suppression. Several mechanisms, such as cell-cell contact in vitro and organ size in vivo, have been implicated in the activation of the Hippo pathway, leading to inactivation of the …
-
Investigating the role of the Hippo pathway in epithelial-mesenchymal transition and drug resistance
The Hippo pathway is an evolutionarily conserved signaling cascade and comprises the core Hippo kinases MST1/2 and LATS1/2, which phosphorylate the transcriptional YES associated protein (YAP), promoting its nuclear exclusion and degradation. Excess YAP activity is oncogenic and is commonly …
-
Characterization of the two major merlin isoforms and merlin regulation of YAP
Merlin is the protein encoded by the tumor suppressor gene NF2. Deletion or loss-of-function of NF2 leads to neurofibromatosis type 2, a disease characterized by the formation of multiple benign tumors of the nervous system. In addition to the genetic disorder, loss of merlin expression has been …
-
Role of the Ajuba LIM Proteins in Epithelial Growth Regulation
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 …
-
Mechanistic Elucidation of the Function of Sirtuin 6 in the Regulation of Liver Fibrosis
… that is initiated upon prolonged damage to the liver, resulting in an accumulation of excess extracellular matrix. This eventually leads to the formation of scar tissue, which disrupts the hepatic architecture and causes liver dysfunction. Hepatic stellate cells (HSCs) play a major role in …
-
Characterizing the Nuclear Function of the Cell Adhesion Molecule Fat and Chromatin Regulation by the Inner Nuclear Membrane Protein Speg
… to animal development. Coordination of these aspects requires elegant signal transduction systems. In Drosophila, fat (ft) encodes an enormous atypical cadherin that is important for such coordination. Ft functions at the cell surface, regulating tissue growth through the Hippo pathway …
-
Identification and Characterization of the TGFβ/Hippo Crosstalk through Mathematical Modeling
… of most developmental and homeostatic processes. The Hippo pathway is a major regulator of tissue growth and organ size. Hippo and TGFβ pathways are intimately interconnected. Hippo pathway mediators Taz/Yap interact with the TGFβ regulated Smads and when Hippo is activated, the cytoplasmically …
-
The Role of Hippo Signalling in Merlin Null Tumours of the Nervous System
… and schwannomas are mostly benign tumours of the nervous system that currently have no clinically approved treatments apart from surgical resection. The tumour suppressor Moesin-Ezrin-Radixin-Like Protein (Merlin) is deleted in 50-60% and 70% of meningiomas and schwannomas respectively. The …
-
YAP/TAZ REGULATES ALVEOLAR REGENERATION AND RESOLUTION OF LUNG INFLAMMATION
Alveolar epithelium plays a pivotal role in protecting the lungs from inhaled infectious agents. Therefore, the regenerative capacity of the alveolar epithelium is critical for recovery from these insults to rebuild the epithelial barrier and restore pulmonary functions. Here, we show that …
-
Functional Regulation of Yap By Aurora A Kinase In Triple-Negative Breast Cancer
<p>The Yes-associated protein (YAP) is an effector that transduces the output of the Hippo pathway to transcriptional modulation. Considering the role of YAP in cancers, this protein has emerged as a key node in malignancy development. In this study, we determined that Aurora A kinase acts as a …
-
Adherens Junctions and The Actomyosin Network Regulate Organ Growth By Modulating Hippo Pathway Activity In Drosophila
… (AJs) and basolateral modules are important for the establishment and maintenance of apico-basal polarity. Loss of AJs and basolateral module members lead to tumor formation, as well as poor prognosis for metastasis. Recently, in mammalian studies it has been shown that loss of either AJ or …
-
Zebrafish Posterior Lateral Line Organogenesis Regulation by Notch Signaling
Organ morphogenesis depends on the precise orchestration of cell migration, cell fate specification and cell shape chages. Results in this thesis demonstrate that Notch signaling is an integral part of the feedback loop between Wnt and Fgf signaling that underlies the self‐organization of …
-
Preliminary Study on How Tumor Suppressor Nf2 Inhibits Transcriptional Coactivators Yap/Taz in the Developing Mouse Brain
… progenitor proliferation and differentiation, the mechanism of which is not well known. Recently the tumor suppressor neurofibromatosis 2 (Nf2) was shown to regulate the balance of neural progenitor proliferation and differentiation in the developing mouse brain through the Hippo pathway …
-
Development of Bioluminescent Biosensors Monitoring Activity of the Merlin Tumour Suppressor
All solid tumours share the ability to circumvent or overcome contact inhibition of proliferation (CIP), the process by which cell-cell contacts engage signalling to stop proliferation. Merlin, an ERM-like protein, plays a crucial role in CIP and is inactivated in a wide variety of cancers, …
-
The Role of YAP/TAZ in von Willebrand Factor Gene Expression
… with important procoagulant roles in the circulation, including mediating platelet adhesion at sites of vascular injury and stabilizing Factor VIII in the plasma. VWF expression and activity is critically regulated to protect against pathological bleeding or thrombotic events, although …
-
Development of drug screening assays for identification of new molecules against pancreatic ductal adenocarcinoma
The yes-associated protein, YAP, is a transcriptional co-activator, able to regulate the expression level of a wide range of target genes. Despite deregulation of YAP has been associated with cancer etiology, no compounds are known to specifically modulate its functions. Here we identified an …
-
The Potential of CRL4-DCAF1 and KSR1 as Therapeutic Targets in Low-grade Merlin-Deficient Tumours
… including schwannoma, meningioma and ependymoma. These tumours can occur sporadically or as part of the genetic condition Neurofibromatosis type 2 (NF2) and cause significant morbidity. The current treatment options are restricted to surgery and radiotherapy, which are invasive and may cause …
Page 1 of 2