{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/86436"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/86436","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"ETS1 and Tumor Heterogeneity: Uncovering Novel Roles of ETS1 within Intrinsic Subtypes of Epithelial Cancers","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["Gluck, Christian; 0000-0001-7437-7204"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Sinha, Satrajit","Biochemistry"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-02-21T17:22:24Z","date_published":"2025-02-21T17:22:24Z","updated_at":"2026-07-27T19:05:32Z","subjects":["biochemistry","bioinformatics","genetics"],"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/10477/86436","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Sinha, Satrajit","Biochemistry"]},{"key":"dc:creator","label":"Author","values":["Gluck, Christian; 0000-0001-7437-7204"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-02-21T17:22:24Z","2020"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["biochemistry","bioinformatics","genetics"]}]},{"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/10477/86436"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","Large-scale sequencing of human tumors has revealed tremendous intra and inter-tumor heterogeneity. Indeed, tumor-to-tumor variations in genetic mutations, epigenetic aberrations and gene expression are recognized in almost every type of cancer. However, current therapies to treat cancer often do not take into account tumor heterogeneity. Hence, understanding the specific driving forces behind different intrinsic subtypes of tumors will facilitate better understanding of cancer etiology and more effective targeted cancer therapies. Transcriptional dysregulated programs, which dictate the expression of genes that define tumor phenotype and inherent heterogeneity are often driven by the function of crucial transcription factors. Identification and molecular characterization of such transcription factors that serve as major regulators of genes and pathways are likely to offer new insights into fundamental mechanisms of cancer biology as well as unveil novel avenues for therapeutic interventions in cancer. Here we have focused our studies on ETS1, an oncogenic transcription factor and examined its functional role in governing dysregulated transcriptional networks in specific subtypes of both Breast Cancer (BRCA) and Head and Neck Squamous Cell Carcinoma (HNSCC). We discovered that ETS1 is preferentially over-expressed in the Basal and Claudin-Low subtypes of BRCA as well as the Mesenchymal subtype of HNSCC, which are all aggressive forms of cancer that currently lack targeted therapy. By using a comprehensive molecular, genetic and bioinformatics driven analysis, we have identified direct transcriptional targets of ETS1 in cell-line models of the aforementioned cancer subtypes. Our integrative approach has uncovered core gene-signatures that highlight ETS1 as a crucial regulator of several oncogenic processes that are intrinsically linked to the phenotypes that define specific subtypes of BRCA and HNSCC. Collectively our studies have revealed the mechanisms by which ETS1 drives epithelial tumorigenesis and in a broader context, identified the key transcriptional networks to which ETS1high tumors are addicted for growth and survival. These findings can be exploited for rational cancer therapies by leveraging the knowledge of novel ETS1 targets that those tumors are likely to be vulnerable to, importantly in the context of a defined molecular tumor subtype.","**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":["ETS1 and Tumor Heterogeneity: Uncovering Novel Roles of ETS1 within Intrinsic Subtypes of Epithelial Cancers"]}]}],"canonical_facts":{"dc:contributor":["Sinha, Satrajit","Biochemistry"],"dc:creator":["Gluck, Christian; 0000-0001-7437-7204"],"dc:date":["2025-02-21T17:22:24Z","2020"],"dc:description":["Ph.D.","Large-scale sequencing of human tumors has revealed tremendous intra and inter-tumor heterogeneity. Indeed, tumor-to-tumor variations in genetic mutations, epigenetic aberrations and gene expression are recognized in almost every type of cancer. However, current therapies to treat cancer often do not take into account tumor heterogeneity. Hence, understanding the specific driving forces behind different intrinsic subtypes of tumors will facilitate better understanding of cancer etiology and more effective targeted cancer therapies. Transcriptional dysregulated programs, which dictate the expression of genes that define tumor phenotype and inherent heterogeneity are often driven by the function of crucial transcription factors. Identification and molecular characterization of such transcription factors that serve as major regulators of genes and pathways are likely to offer new insights into fundamental mechanisms of cancer biology as well as unveil novel avenues for therapeutic interventions in cancer. Here we have focused our studies on ETS1, an oncogenic transcription factor and examined its functional role in governing dysregulated transcriptional networks in specific subtypes of both Breast Cancer (BRCA) and Head and Neck Squamous Cell Carcinoma (HNSCC). We discovered that ETS1 is preferentially over-expressed in the Basal and Claudin-Low subtypes of BRCA as well as the Mesenchymal subtype of HNSCC, which are all aggressive forms of cancer that currently lack targeted therapy. By using a comprehensive molecular, genetic and bioinformatics driven analysis, we have identified direct transcriptional targets of ETS1 in cell-line models of the aforementioned cancer subtypes. Our integrative approach has uncovered core gene-signatures that highlight ETS1 as a crucial regulator of several oncogenic processes that are intrinsically linked to the phenotypes that define specific subtypes of BRCA and HNSCC. Collectively our studies have revealed the mechanisms by which ETS1 drives epithelial tumorigenesis and in a broader context, identified the key transcriptional networks to which ETS1high tumors are addicted for growth and survival. These findings can be exploited for rational cancer therapies by leveraging the knowledge of novel ETS1 targets that those tumors are likely to be vulnerable to, importantly in the context of a defined molecular tumor subtype.","**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/10477/86436"],"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":["biochemistry","bioinformatics","genetics"],"dc:title":["ETS1 and Tumor Heterogeneity: Uncovering Novel Roles of ETS1 within Intrinsic Subtypes of Epithelial Cancers"],"dc:type":["Text","Dissertation"]},"updated_at":"2026-07-27T19:05:32Z"}