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You searched for +publisher:"Vanderbilt University" +contributor:("Dr. Alissa M. Weaver"). Showing records 1 – 3 of 3 total matches.

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Vanderbilt University

1. Sinha, Seema. A Novel Role of Cortactin in Exosome Secretion and Tumor Progression.

Degree: PhD, Cancer Biology, 2016, Vanderbilt University

Exosomes are extracellular vesicles that carry a variety of RNA and protein cargos, including growth factors, transmembrane proteins, angiogenic factors, proteinases, and microRNA. However, the mechanisms that regulate exosome secretion are still poorly understood. This dissertation work shows that the tumor-overexpressed cytoskeletal protein cortactin promotes exosome secretion. Knockdown or overexpression of cortactin in head and neck squamous cell carcinoma, fibrosarcoma, and breast cancer cells leads to a corresponding decrease or increase in exosome secretion. However, cortactin knockdown does not affect cargo sorting or exosome biogenesis. Rescue experiments carried out by adding purified exosomes back to cortactin-knockdown cells suggest that exosome secretion may account for many functions of cortactin in tumor aggressiveness. Furthermore, live imaging revealed that cortactin controls both trafficking and plasma membrane docking of multivesicular endosomes. Mechanistically, interaction of cortactin with Arp2/3 complex and branched actin is critical for exosome secretion. Also, cortactin, Rab27a, and coronin 1b coordinately control stability of cortical actin multivesicular endosome docking sites along with exosome secretion. Overall, this dissertation identifies molecular and cellular mechanisms important for exosome secretion. Advisors/Committee Members: Dr. Robert J. Coffey (committee member), Dr. Matthew J. Tyska (committee member), Dr. Rebecca A. Ihrie (committee member), Dr. Alissa M. Weaver (committee member), Dr. Rebecca S. Cook (chair).

Subjects/Keywords: Cancer; Endosomes; Cytoskeleton; Exosomes; Actin; Cortactin

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APA (6th Edition):

Sinha, S. (2016). A Novel Role of Cortactin in Exosome Secretion and Tumor Progression. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://etd.library.vanderbilt.edu/available/etd-07212016-161343/ ;

Chicago Manual of Style (16th Edition):

Sinha, Seema. “A Novel Role of Cortactin in Exosome Secretion and Tumor Progression.” 2016. Doctoral Dissertation, Vanderbilt University. Accessed April 03, 2020. http://etd.library.vanderbilt.edu/available/etd-07212016-161343/ ;.

MLA Handbook (7th Edition):

Sinha, Seema. “A Novel Role of Cortactin in Exosome Secretion and Tumor Progression.” 2016. Web. 03 Apr 2020.

Vancouver:

Sinha S. A Novel Role of Cortactin in Exosome Secretion and Tumor Progression. [Internet] [Doctoral dissertation]. Vanderbilt University; 2016. [cited 2020 Apr 03]. Available from: http://etd.library.vanderbilt.edu/available/etd-07212016-161343/ ;.

Council of Science Editors:

Sinha S. A Novel Role of Cortactin in Exosome Secretion and Tumor Progression. [Doctoral Dissertation]. Vanderbilt University; 2016. Available from: http://etd.library.vanderbilt.edu/available/etd-07212016-161343/ ;

2. Potdar, Alka Anand. Characterizing eukaryotic single cell motility via bimodal analysis.

Degree: PhD, Chemical Engineering, 2009, Vanderbilt University

Bimodal analysis, a cellular-scale approach to studying eukaryotic single cell migration by performing a model-based analysis of single cell video-microscopy data, is described. The bimodal framework that is a generalization of the run-and-tumble motion of bacteria segregates the cellular trajectories into two types of alternating modes, namely, the "directional-mode" (the more persistent mode, analogous to the bacterial run phase) and the "re-orientation-mode" (the less persistent mode, analogous to the bacterial tumble phase). The dissertation research reported here has three main aspects. The first is the measurement of epithelial single cell migration by video-microscopy, which is then characterized using a simple model-based tool, bimodal analysis, developed as part of this dissertation research. The second aspect is to model mammary epithelial single cell migration by means of a cellular dynamics simulation methodology and using a bimodal correlated random walk (BCRW) model. The BCRW model was developed to elucidate the search strategy of single epithelial cells from multi-cellular organisms. The third aspect deals with application of bimodal analysis tool to eclectic eukaryotic cell types (Dictyostelium, neutrophils, fibrosarcoma, prostate cancer in addition to mammary epithelial cells) in different motility assays/treatments to provide a common framework for studying eukaryotic single cell motility. In addition, a simple experimental setup for creating a temporal gradient of chemo-attractant for epithelial cells is described and the possibility of temporal gradient sensing by epithelial cells is studied. Advisors/Committee Members: Dr. Clare McCabe (committee member), Dr. G. Kane Jennings (committee member), Dr. Scott A. Guelcher (committee member), Dr. Alissa M. Weaver (committee member), Dr. Peter T. Cummings (chair).

Subjects/Keywords: mammary epithelial cells; video-microscopy; bimodal framework; cell migration

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

APA (6th Edition):

Potdar, A. A. (2009). Characterizing eukaryotic single cell motility via bimodal analysis. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://etd.library.vanderbilt.edu/available/etd-12152009-103435/ ;

Chicago Manual of Style (16th Edition):

Potdar, Alka Anand. “Characterizing eukaryotic single cell motility via bimodal analysis.” 2009. Doctoral Dissertation, Vanderbilt University. Accessed April 03, 2020. http://etd.library.vanderbilt.edu/available/etd-12152009-103435/ ;.

MLA Handbook (7th Edition):

Potdar, Alka Anand. “Characterizing eukaryotic single cell motility via bimodal analysis.” 2009. Web. 03 Apr 2020.

Vancouver:

Potdar AA. Characterizing eukaryotic single cell motility via bimodal analysis. [Internet] [Doctoral dissertation]. Vanderbilt University; 2009. [cited 2020 Apr 03]. Available from: http://etd.library.vanderbilt.edu/available/etd-12152009-103435/ ;.

Council of Science Editors:

Potdar AA. Characterizing eukaryotic single cell motility via bimodal analysis. [Doctoral Dissertation]. Vanderbilt University; 2009. Available from: http://etd.library.vanderbilt.edu/available/etd-12152009-103435/ ;

3. Barnes, Stephanie Lynne. Interrogation of the Limitations and Capabilities of the Model-Gel-Tissue Assay and Application to Soft Tissue Modulus Evaluation.

Degree: PhD, Biomedical Engineering, 2011, Vanderbilt University

The correlation between changes in mechanical properties and the onset of disease has led to an increased interest in assessing the elastic modulus of soft tissues as a biomarker for disease progression. In addition, soft tissue mechanical properties are desired for biomechanical modeling for surgical procedure planning and intraoperative guidance. Unfortunately, soft tissue modulus evaluation has proven inherently difficult due to tissue consistency and shape, and the approaches are highly variant. The work presented in this thesis focuses on the development, application, and interrogation of a novel soft tissue mechanical property evaluation technique, termed the Model-Gel-Tissue (MGT) assay, which utilizes a combination of a gel embedding process, direct mechanical testing, and computational modeling to analyze the elastic properties of a soft tissue sample. The goal was to develop a repeatable and adaptable evaluation technique that also allowed for irregularly shaped specimens and standardization of the implementation. This was accomplished by a rapid-embedding of the tissue in a gel with surfaces of known and uniform shape. The mechanical testing output is then utilized in a finite element model of the system developed from computed tomography (CT) scans of the specimen, in order to evaluate the mechanical properties of the embedded tissue. Preliminary testing of the MGT assay was implemented using fibrotic murine livers to assess the capability of the technique relative to traditional indentation testing. The assay was then used to investigate the correlation between microstructural collagen content and macroscopic tissue modulus in a murine model of breast cancer. Subsequently, the assay was used to investigate the propensity of modulus as an indicator of treatment resistance in a second murine model of breast cancer. Finally, extensive sensitivity tests were performed to qualify the fidelity of the system. The results of this work show that modulus assessment via the MGT assay correlates to traditional testing, as well as to tissue collagen content, and the concatenation of the work indicates that the MGT assay serves as a reliable and adaptable soft tissue modulus evaluation system. Advisors/Committee Members: Dr. Michael I. Miga (chair), Dr. John C. Gore (committee member), Dr. Robert J. Roselli (committee member), Dr. Alissa M. Weaver (committee member), Dr. Thomas E. Yankeelov (committee member).

Subjects/Keywords: finite element modeling; mechanical properties; young's modulus; elastic modulus; material testing

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

APA (6th Edition):

Barnes, S. L. (2011). Interrogation of the Limitations and Capabilities of the Model-Gel-Tissue Assay and Application to Soft Tissue Modulus Evaluation. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://etd.library.vanderbilt.edu/available/etd-03242011-144611/ ;

Chicago Manual of Style (16th Edition):

Barnes, Stephanie Lynne. “Interrogation of the Limitations and Capabilities of the Model-Gel-Tissue Assay and Application to Soft Tissue Modulus Evaluation.” 2011. Doctoral Dissertation, Vanderbilt University. Accessed April 03, 2020. http://etd.library.vanderbilt.edu/available/etd-03242011-144611/ ;.

MLA Handbook (7th Edition):

Barnes, Stephanie Lynne. “Interrogation of the Limitations and Capabilities of the Model-Gel-Tissue Assay and Application to Soft Tissue Modulus Evaluation.” 2011. Web. 03 Apr 2020.

Vancouver:

Barnes SL. Interrogation of the Limitations and Capabilities of the Model-Gel-Tissue Assay and Application to Soft Tissue Modulus Evaluation. [Internet] [Doctoral dissertation]. Vanderbilt University; 2011. [cited 2020 Apr 03]. Available from: http://etd.library.vanderbilt.edu/available/etd-03242011-144611/ ;.

Council of Science Editors:

Barnes SL. Interrogation of the Limitations and Capabilities of the Model-Gel-Tissue Assay and Application to Soft Tissue Modulus Evaluation. [Doctoral Dissertation]. Vanderbilt University; 2011. Available from: http://etd.library.vanderbilt.edu/available/etd-03242011-144611/ ;

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