{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/84091"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/84091","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Role of FAK and Small G-protein Signaling in Vascular Smooth Muscle Spheroid Formation","abstract":"M.A.","abstract_html":"M.A.","abstract_has_math":false,"creators":["Vaidyanathan, Kalyanaraman; 0000-0002-7934-2382"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Bae, Yongho","Pathology and Anatomical Sciences"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-06-21T15:47:50Z","date_published":"2022-06-21T15:47:50Z","updated_at":"2026-07-27T19:05:30Z","subjects":["pathology"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/84091","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Bae, Yongho","Pathology and Anatomical Sciences"]},{"key":"dc:creator","label":"Author","values":["Vaidyanathan, Kalyanaraman; 0000-0002-7934-2382"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2022-06-21T15:47:50Z","2019"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["pathology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/84091"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["M.A.","Uncontrolled proliferation of vascular smooth muscle cells (VSMCs) is the main feature of vascular injury and atherosclerosis, where VSMCs transition from differentiated to a de-differentiated state, in which they exhibit increased proliferation, and extracellular matrix (ECM) production that constitute a substantial part of the neointima (NI). Integrin-mediated focal adhesion kinase (FAK) senses the changes in ECM in atherosclerosis and in response to vascular injury. FAK and downstream small G-proteins (Rac, Rho, and Cdc42) control cell-cell contact formation and play a key role in vascular pathology. In this research project, I tested the importance of FAK and downstream small G-proteins in VSMC spheroid formation, as a model to study NI formation. VSMC spheroids were made using hanging drop culture in the presence of inhibitors of FAK, or downstream small G-proteins, or vehicle control (DMSO). A machine-learning-based image segmentation called a vU-net was used to segment and display the variations in the morphology of spheroids in response to the treatment. Spheroid boundaries were manually drawn on a subset of images using Pixel Annotation Tool software, to train the vU-net. The trained algorithm identified boundaries with 95% accuracy. A two-level framework (coarse and fine-tune) of k-means clustering was used to group VSMC spheroids into different morphologies. Drug treatment disrupted spheroid morphology, indicating that FAK and downstream small G-proteins are required for normal spheroid formation. Inhibition of FAK, Rac and Rho, but not Cdc42 caused a significant reduction in N-cadherin. Thus, FAK-Rac/Rho-N-cadherin pathways could potentially regulate spheroid formation. Another exciting observation is the presence of various morphologies of disrupted spheroids resulting from the treatment of inhibitors. Coarse clustering analysis showed the presence of two clusters of a spheroid with rounded morphology and 2 clusters disrupted spheroid morphologies. Moreover, fine-tune clustering analysis identified the presence of four morphological clusters among the disrupted spheroids. Collectively, studying the biological implications of the spheroid morphologies could potentially aid in exploring better therapeutic agents to target NI formation and treatment.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Role of FAK and Small G-protein Signaling in Vascular Smooth Muscle Spheroid Formation"]}]}],"canonical_facts":{"dc:contributor":["Bae, Yongho","Pathology and Anatomical Sciences"],"dc:creator":["Vaidyanathan, Kalyanaraman; 0000-0002-7934-2382"],"dc:date":["2022-06-21T15:47:50Z","2019"],"dc:description":["M.A.","Uncontrolled proliferation of vascular smooth muscle cells (VSMCs) is the main feature of vascular injury and atherosclerosis, where VSMCs transition from differentiated to a de-differentiated state, in which they exhibit increased proliferation, and extracellular matrix (ECM) production that constitute a substantial part of the neointima (NI). Integrin-mediated focal adhesion kinase (FAK) senses the changes in ECM in atherosclerosis and in response to vascular injury. FAK and downstream small G-proteins (Rac, Rho, and Cdc42) control cell-cell contact formation and play a key role in vascular pathology. In this research project, I tested the importance of FAK and downstream small G-proteins in VSMC spheroid formation, as a model to study NI formation. VSMC spheroids were made using hanging drop culture in the presence of inhibitors of FAK, or downstream small G-proteins, or vehicle control (DMSO). A machine-learning-based image segmentation called a vU-net was used to segment and display the variations in the morphology of spheroids in response to the treatment. Spheroid boundaries were manually drawn on a subset of images using Pixel Annotation Tool software, to train the vU-net. The trained algorithm identified boundaries with 95% accuracy. A two-level framework (coarse and fine-tune) of k-means clustering was used to group VSMC spheroids into different morphologies. Drug treatment disrupted spheroid morphology, indicating that FAK and downstream small G-proteins are required for normal spheroid formation. Inhibition of FAK, Rac and Rho, but not Cdc42 caused a significant reduction in N-cadherin. Thus, FAK-Rac/Rho-N-cadherin pathways could potentially regulate spheroid formation. Another exciting observation is the presence of various morphologies of disrupted spheroids resulting from the treatment of inhibitors. Coarse clustering analysis showed the presence of two clusters of a spheroid with rounded morphology and 2 clusters disrupted spheroid morphologies. Moreover, fine-tune clustering analysis identified the presence of four morphological clusters among the disrupted spheroids. Collectively, studying the biological implications of the spheroid morphologies could potentially aid in exploring better therapeutic agents to target NI formation and treatment.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/84091"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["pathology"],"dc:title":["Role of FAK and Small G-protein Signaling in Vascular Smooth Muscle Spheroid Formation"],"dc:type":["Text","Thesis"]},"updated_at":"2026-07-27T19:05:30Z"}