{"id":{"repo_id":"wustl","oai_identifier":"oai:openscholarship.wustl.edu:etd-1390"},"canonical_url":"https://search.dev.ndltd.org/etd/wustl/oai:openscholarship.wustl.edu:etd-1390","repository":{"repo_id":"wustl","name":"Washington University in St. Louis","base_url":"https://openscholarship.wustl.edu/do/oai/"},"display":{"title":"Targeting The Dimerization Of ERBB Receptor Tyrosine Kinases","abstract":"The epidermal growth factor receptor: EGFR) is a membrane receptor tyrosine kinase whose over-activation has been implicated to cause many human cancers. Novel strategies to inhibit the activation of EGF receptors other than the conventional antibody-based and tyrosine kinase inhibitors are virtually non-existent but could provide benefits both in the laboratory and clinical settings. In an effort to expand the current approaches, this thesis focused on targeting the homodimerization of the EGF receptors themselves and the heterodimerization of EGF receptors with the related ErbB2 receptor. Three sub-projects were completed in the process. The first project explored the feasibility of inhibiting the EGF receptor by targeting receptor dimerization with small molecules. Two lead compounds were initially predicted by virtual screening the NCI compound library, and were biochemically characterized. The benefit gained from the application of virtual screening in this project initiated another project to enhance the accessibility of virtual screening within the non-computational community. The OpenScreening project utilizes distributed computing resources and provides open-access screening server at: http://omg.phy.umassd.edu/xvhts. A final project identified the structural mechanism that may explain the observed preference of EGFR-ErbB2 heterodimerization over EGFR homodimerization. Key residues were computationally predicted and biochemically tested to reveal critical dimerization interface.","abstract_html":"The epidermal growth factor receptor: EGFR) is a membrane receptor tyrosine kinase whose over-activation has been implicated to cause many human cancers. Novel strategies to inhibit the activation of EGF receptors other than the conventional antibody-based and tyrosine kinase inhibitors are virtually non-existent but could provide benefits both in the laboratory and clinical settings. In an effort to expand the current approaches, this thesis focused on targeting the homodimerization of the EGF receptors themselves and the heterodimerization of EGF receptors with the related ErbB2 receptor. Three sub-projects were completed in the process. The first project explored the feasibility of inhibiting the EGF receptor by targeting receptor dimerization with small molecules. Two lead compounds were initially predicted by virtual screening the NCI compound library, and were biochemically characterized. The benefit gained from the application of virtual screening in this project initiated another project to enhance the accessibility of virtual screening within the non-computational community. The OpenScreening project utilizes distributed computing resources and provides open-access screening server at: http://omg.phy.umassd.edu/xvhts. A final project identified the structural mechanism that may explain the observed preference of EGFR-ErbB2 heterodimerization over EGFR homodimerization. Key residues were computationally predicted and biochemically tested to reveal critical dimerization interface.","abstract_has_math":false,"creators":["Yang, Rob"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Biology and Biomedical Sciences: Computational and Systems Biology","degree_department":null,"school":null,"contributors":["Garland Marshall"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2009,"date_issued":"2009-01-01T08:00:00Z","date_published":"2009-01-01T08:00:00Z","updated_at":"2026-07-24T06:12:25Z","subjects":["Biology","Cell","General","Molecular","dimerization","EGFR","openscreening","protein-protein interaction","virtual screening","xgrid"],"languages":["English (en)"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.7936/K7VQ30NW"],"render_values":[{"text":"https://doi.org/10.7936/K7VQ30NW","href":"https://doi.org/10.7936/K7VQ30NW","code":true}]}]},"links":{"outbound_url":"https://openscholarship.wustl.edu/etd/391","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Garland Marshall"]},{"key":"dc:creator","label":"Author","values":["Yang, Rob"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2010-01-01T08:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biology and Biomedical Sciences: Computational and Systems Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biology","Cell","General","Molecular","dimerization","EGFR","openscreening","protein-protein interaction","virtual screening","xgrid"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English (en)"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://openscholarship.wustl.edu/etd/391"]},{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.7936/K7VQ30NW"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The epidermal growth factor receptor: EGFR) is a membrane receptor tyrosine kinase whose over-activation has been implicated to cause many human cancers. Novel strategies to inhibit the activation of EGF receptors other than the conventional antibody-based and tyrosine kinase inhibitors are virtually non-existent but could provide benefits both in the laboratory and clinical settings. In an effort to expand the current approaches, this thesis focused on targeting the homodimerization of the EGF receptors themselves and the heterodimerization of EGF receptors with the related ErbB2 receptor. Three sub-projects were completed in the process. The first project explored the feasibility of inhibiting the EGF receptor by targeting receptor dimerization with small molecules. Two lead compounds were initially predicted by virtual screening the NCI compound library, and were biochemically characterized. The benefit gained from the application of virtual screening in this project initiated another project to enhance the accessibility of virtual screening within the non-computational community. The OpenScreening project utilizes distributed computing resources and provides open-access screening server at: http://omg.phy.umassd.edu/xvhts. A final project identified the structural mechanism that may explain the observed preference of EGFR-ErbB2 heterodimerization over EGFR homodimerization. Key residues were computationally predicted and biochemically tested to reveal critical dimerization interface."]},{"key":"dc:title","label":"Title","values":["Targeting The Dimerization Of ERBB Receptor Tyrosine Kinases"]}]}],"canonical_facts":{"dc:contributor":["Garland Marshall"],"dc:creator":["Yang, Rob"],"dc:date.available":["2010-01-01T08:00:00Z"],"dc:description.abstract":["The epidermal growth factor receptor: EGFR) is a membrane receptor tyrosine kinase whose over-activation has been implicated to cause many human cancers. Novel strategies to inhibit the activation of EGF receptors other than the conventional antibody-based and tyrosine kinase inhibitors are virtually non-existent but could provide benefits both in the laboratory and clinical settings. In an effort to expand the current approaches, this thesis focused on targeting the homodimerization of the EGF receptors themselves and the heterodimerization of EGF receptors with the related ErbB2 receptor. Three sub-projects were completed in the process. The first project explored the feasibility of inhibiting the EGF receptor by targeting receptor dimerization with small molecules. Two lead compounds were initially predicted by virtual screening the NCI compound library, and were biochemically characterized. The benefit gained from the application of virtual screening in this project initiated another project to enhance the accessibility of virtual screening within the non-computational community. The OpenScreening project utilizes distributed computing resources and provides open-access screening server at: http://omg.phy.umassd.edu/xvhts. A final project identified the structural mechanism that may explain the observed preference of EGFR-ErbB2 heterodimerization over EGFR homodimerization. Key residues were computationally predicted and biochemically tested to reveal critical dimerization interface."],"dc:identifier":["https://openscholarship.wustl.edu/etd/391"],"dc:identifier.doi":["https://doi.org/10.7936/K7VQ30NW"],"dc:language":["English (en)"],"dc:subject":["Biology","Cell","General","Molecular","dimerization","EGFR","openscreening","protein-protein interaction","virtual screening","xgrid"],"dc:title":["Targeting The Dimerization Of ERBB Receptor Tyrosine Kinases"],"thesis:degree_discipline":["Biology and Biomedical Sciences: Computational and Systems Biology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T06:12:25Z"}