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You searched for +publisher:"University of Texas Southwestern Medical Center" +contributor:("Danuser, Gaudenz"). Showing records 1 – 3 of 3 total matches.

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University of Texas Southwestern Medical Center

1. Connelly, Sarah Elkin. Regulation of Clathrin Mediated Endocytosis and Its Role in Cancer Progression.

Degree: 2017, University of Texas Southwestern Medical Center

Metastasis is a multistep process requiring cancer cell signaling, invasion, migration, survival, and proliferation. These processes require dynamic modulation of cell surface proteins by endocytosis. Given this functional connection, it has been suggested that endocytosis is dysregulated in cancer. To test this, we developed In-Cell ELISA assays to measure three different endocytic pathways: clathrin-mediated endocytosis, caveolae-mediated endocytosis, and clathrin-independent endocytosis and compared these activities in 29 independently isolated non-small cell lung cancer (NSCLC) cell lines to determine whether there were systematic changes in the three different endocytic pathways. However we observed significant heterogeneity. Nonetheless, using hierarchical clustering based on their combined endocytic properties we identified two phenotypically distinct clusters of NSCLCs. One co-clustered with mutations in KRAS, a mesenchymal phenotype, increased invasion through collagen and decreased growth in soft agar, whereas the second was enriched in cells with an epithelial phenotype. We also used the In-Cell ELISA assay to characterize Ikarugamycin (IKA), a previously discovered antibiotic, which inhibits the uptake of oxidized low-density lipoproteins in macrophages, as well as clathrin-mediated endocytosis (CME) in plant cell lines. However, detailed characterization of IKA had yet been performed. Therefore, we performed biochemistry and microscopy experiments to further characterize the effects of IKA on CME. We showed that IKA acutely inhibits CME, but not other endocytic pathways with an IC50 of 2.7 μM. Although long-term incubation with IKA has cytotoxic effects, the short-term inhibitory effects on CME were reversible. Thus, IKA can be a useful tool for probing routes of endocytic trafficking. Finally, we investigated possible mechanisms that lead to altered endocytosis in cancer cells. We discovered that dynamin 1 (Dyn1), previously thought to be neuron specific is frequently upregulated and postranslationally regulated in cancer cells. Dyn1 expression alters the proliferation rates, growth in soft agar, and tumor growth of cancer cells. We hypothesize that these changes are due to alteration in cell surface protein expression and downstream signaling pathways and have developed protocols to test these hypothesizes. Taken together, our results suggest that endocytic alterations in cancer cells can significantly influence cancer-relevant phenotypes. Advisors/Committee Members: Minna, John D., Schmid, Sandra, Shay, Jerry W., Danuser, Gaudenz.

Subjects/Keywords: Carcinoma, Non-Small-Cell Lung; Clathrin; Endocytosis; Lactams; Lung Neoplasms

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Connelly, S. E. (2017). Regulation of Clathrin Mediated Endocytosis and Its Role in Cancer Progression. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/7182

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Connelly, Sarah Elkin. “Regulation of Clathrin Mediated Endocytosis and Its Role in Cancer Progression.” 2017. Thesis, University of Texas Southwestern Medical Center. Accessed July 09, 2020. http://hdl.handle.net/2152.5/7182.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Connelly, Sarah Elkin. “Regulation of Clathrin Mediated Endocytosis and Its Role in Cancer Progression.” 2017. Web. 09 Jul 2020.

Vancouver:

Connelly SE. Regulation of Clathrin Mediated Endocytosis and Its Role in Cancer Progression. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2017. [cited 2020 Jul 09]. Available from: http://hdl.handle.net/2152.5/7182.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Connelly SE. Regulation of Clathrin Mediated Endocytosis and Its Role in Cancer Progression. [Thesis]. University of Texas Southwestern Medical Center; 2017. Available from: http://hdl.handle.net/2152.5/7182

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


University of Texas Southwestern Medical Center

2. Wang, Chensu. Illuminating Endocytic Organelles with pH-Resposive [sic] Nanomaterials.

Degree: 2017, University of Texas Southwestern Medical Center

Endosomes, lysosomes and related catabolic organelles are a dynamic continuum of vacuolar structures that impact a number of key cell physiological processes that include protein/lipid metabolism, nutrient sensing and cell survival. To support quantitative investigation of these processes in living cells, we have developed a library of ultra-pH sensitive (UPS) fluorescent nanoparticles with chemical properties that allow fine-scale, multiplexed, spatial-temporal perturbation and quantification of catabolic organelle maturation at single organelle resolution. Deployment in cells enabled quantification of the proton accumulation rate in endosomes; illumination of previously unrecognized regulatory mechanisms coupling pH transitions to endosomal coat protein exchange; discovery of distinct pH thresholds required for mTORC1 activation by free amino acids versus proteins; broad-scale characterization of the consequence of endosomal pH transitions on cellular metabolomic profiles; and functionalization of a context-specific metabolic vulnerability in lung cancer cells. These biological applications benchmarked the robustness and adaptability of this nanotechnology-enabled 'detect and perturb' strategy. As a translational application, we leveraged the technology in high-throughput screening assays that successfully identified chemical agents in the promotion of autophagolysosomal activity through TFEB activation. Formulation of these compounds in liver-tropic biodegradable, biocompatible nanoparticles conferred hepatoprotection against diet-induced steatosis in murine models and prolonged survival in Caenorhabditis elegans. These results highlight the therapeutic potential of small-molecule TFEB activators to ameliorate metabolic syndrome and extend lifespan. Advisors/Committee Members: DeBerardinis, Ralph J., White, Michael A., Gao, Jinming, Danuser, Gaudenz, Yoo, Hyuntae, Zhong, Qing.

Subjects/Keywords: Endocytosis; Endosomes; Fluorescent Dyes; Lysosomes; Nanoparticles

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Wang, C. (2017). Illuminating Endocytic Organelles with pH-Resposive [sic] Nanomaterials. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/6595

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Wang, Chensu. “Illuminating Endocytic Organelles with pH-Resposive [sic] Nanomaterials.” 2017. Thesis, University of Texas Southwestern Medical Center. Accessed July 09, 2020. http://hdl.handle.net/2152.5/6595.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Wang, Chensu. “Illuminating Endocytic Organelles with pH-Resposive [sic] Nanomaterials.” 2017. Web. 09 Jul 2020.

Vancouver:

Wang C. Illuminating Endocytic Organelles with pH-Resposive [sic] Nanomaterials. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2017. [cited 2020 Jul 09]. Available from: http://hdl.handle.net/2152.5/6595.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wang C. Illuminating Endocytic Organelles with pH-Resposive [sic] Nanomaterials. [Thesis]. University of Texas Southwestern Medical Center; 2017. Available from: http://hdl.handle.net/2152.5/6595

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


University of Texas Southwestern Medical Center

3. Ozel, Mehmet Neset. Filopodial Dynamics and Synapse Specification in the Drosophila Visual System.

Degree: 2017, University of Texas Southwestern Medical Center

How is the synaptic specificity achieved in neural circuits comprised of hundreds of different types of neurons? My dissertation aims to advance our knowledge on this overarching question using the complex visual processing circuitry of D. melanogaster. This system not only provides excellent genetic amenability but also a model where almost all connectivity can be built without environmental input, i.e. it is genetically hardwired. Nearly three decades of research has identified a vast array of genes required for various steps of synapse specification. However, it remained unclear how these genes implement the developmental rules that result in the final connectivity and we understand very little of what actually goes wrong between a particular genetic perturbation and the resulting miswired circuit. To that end, I focused on the actual subcellular substrate of connectivity: axonal growth cones. To gain access to the details of their dynamic behavior during development, I developed an imaging technique which allows the monitoring of intact, developing fly brains over long periods in high temporal and spatial resolution. Using live imaging and the axonal terminals of R7 photoreceptor as a model, I performed a detailed analysis of growth cone dynamics during various steps of synaptic specification, in wild-type and perturbed conditions. Interestingly, I found that none of the perturbations that were previously tied to 'layer specific targeting' of R7 axons were actually required for the recognition of or targeting to a specific layer; instead, all displayed a loss of stabilization with various timings of onset. High speed live analysis revealed the stochastic filopodial dynamics of these axons as crucial mediators of this stabilization. First, as the substrate of attachment to the target layer during early development (Chapter 2); second, as the searching agents for postsynaptic partners during synapse formation (Chapter 3). In brief, my research provided a valuable bridge between the genetic factors that instruct the synapse specific wiring of the brain and how they regulate the dynamic properties of axonal growth cones and synaptic terminals in distinct ways to achieve that final outcome. Advisors/Committee Members: Terman, Jonathan R., Meeks, Julian P., Danuser, Gaudenz, Huber, Kimberly M., Hiesinger, Peter Robin.

Subjects/Keywords: Drosophila; Growth Cones; Pseudopodia; Visual Pathways

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Ozel, M. N. (2017). Filopodial Dynamics and Synapse Specification in the Drosophila Visual System. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/7745

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Ozel, Mehmet Neset. “Filopodial Dynamics and Synapse Specification in the Drosophila Visual System.” 2017. Thesis, University of Texas Southwestern Medical Center. Accessed July 09, 2020. http://hdl.handle.net/2152.5/7745.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Ozel, Mehmet Neset. “Filopodial Dynamics and Synapse Specification in the Drosophila Visual System.” 2017. Web. 09 Jul 2020.

Vancouver:

Ozel MN. Filopodial Dynamics and Synapse Specification in the Drosophila Visual System. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2017. [cited 2020 Jul 09]. Available from: http://hdl.handle.net/2152.5/7745.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ozel MN. Filopodial Dynamics and Synapse Specification in the Drosophila Visual System. [Thesis]. University of Texas Southwestern Medical Center; 2017. Available from: http://hdl.handle.net/2152.5/7745

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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