{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/78401"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/78401","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"The Role of Fatty Acid Elongase ELOVL6 in Multiple Myeloma Drug Resistance","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["Lipchick, Brittany"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Nikiforov, Mikhail","Roswell Park"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018-10-24T19:38:45Z","date_published":"2018-10-24T19:38:45Z","updated_at":"2026-07-27T19:05:09Z","subjects":["molecular biology","molecular physics","molecular chemistry","biophysics"],"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/10477/78401","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Nikiforov, Mikhail","Roswell Park"]},{"key":"dc:creator","label":"Author","values":["Lipchick, Brittany"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2018-10-24T19:38:45Z","2018","2018-06-07 20:13:59"]},{"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":["molecular biology","molecular physics","molecular chemistry","biophysics"]}]},{"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/10477/78401"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","Multiple myeloma (MM) accounts for approximately 10% of all hematological malignancies and is characterized by the oncogenic transformation of plasma cells, a type of white blood cell that is responsible for producing antibodies. Currently, MM remains incurable however, with the introduction of Bortezomib (BTZ, Velcade), a novel first generation proteasome inhibitor, MM patients survival rates have improved remarkably. Unfortunately, rapidly developing drug resistance has been detrimental for the success of BTZ treatment. It has been concluded that BTZ resistance is most likely due to the combination of several different mechanisms. While many studies have focused on the role of BTZs inability to bind to the proteasome as one cause for BTZ resistance, additional mechanisms of BTZ resistance have yet to be explored. We identified ELOVL6, an elongase in de novo fatty acid metabolism as a key mediator of BTZ resistance in MM. Our work revealed that ELOVL6 expression was suppressed in patients who were not responsive to BTZ, as well as in MM cell lines selected for BTZ resistance. In addition, functional assays revealed that depletion of ELOVL6 by shRNA suppressed BTZ-induced cell death and conversely, overexpression of ELOVL6 facilitated BTZ-induced cell death. More importantly, we found that overexpression of ELOVL6 in BTZ-resistant cells resulted in regaining sensitivity to BTZ treatment. Following lipidomic analysis, we identified that a ELOVL6 product, stearic acid, plays an important role in the cytotoxicity of BTZ. Additionally, we have established a link between ELOVL6, stearic acid and ER stress as a novel mechanism of BTZ induced cytotoxicity and BTZ resistance. For the first time, this establishes the role of fatty acid metabolism in BTZ resistance in MM as well as an attractive therapeutic enzyme for the management of MM."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["The Role of Fatty Acid Elongase ELOVL6 in Multiple Myeloma Drug Resistance"]}]}],"canonical_facts":{"dc:contributor":["Nikiforov, Mikhail","Roswell Park"],"dc:creator":["Lipchick, Brittany"],"dc:date":["2018-10-24T19:38:45Z","2018","2018-06-07 20:13:59"],"dc:description":["Ph.D.","Multiple myeloma (MM) accounts for approximately 10% of all hematological malignancies and is characterized by the oncogenic transformation of plasma cells, a type of white blood cell that is responsible for producing antibodies. Currently, MM remains incurable however, with the introduction of Bortezomib (BTZ, Velcade), a novel first generation proteasome inhibitor, MM patients survival rates have improved remarkably. Unfortunately, rapidly developing drug resistance has been detrimental for the success of BTZ treatment. It has been concluded that BTZ resistance is most likely due to the combination of several different mechanisms. While many studies have focused on the role of BTZs inability to bind to the proteasome as one cause for BTZ resistance, additional mechanisms of BTZ resistance have yet to be explored. We identified ELOVL6, an elongase in de novo fatty acid metabolism as a key mediator of BTZ resistance in MM. Our work revealed that ELOVL6 expression was suppressed in patients who were not responsive to BTZ, as well as in MM cell lines selected for BTZ resistance. In addition, functional assays revealed that depletion of ELOVL6 by shRNA suppressed BTZ-induced cell death and conversely, overexpression of ELOVL6 facilitated BTZ-induced cell death. More importantly, we found that overexpression of ELOVL6 in BTZ-resistant cells resulted in regaining sensitivity to BTZ treatment. Following lipidomic analysis, we identified that a ELOVL6 product, stearic acid, plays an important role in the cytotoxicity of BTZ. Additionally, we have established a link between ELOVL6, stearic acid and ER stress as a novel mechanism of BTZ induced cytotoxicity and BTZ resistance. For the first time, this establishes the role of fatty acid metabolism in BTZ resistance in MM as well as an attractive therapeutic enzyme for the management of MM."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/78401"],"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":["molecular biology","molecular physics","molecular chemistry","biophysics"],"dc:title":["The Role of Fatty Acid Elongase ELOVL6 in Multiple Myeloma Drug Resistance"],"dc:type":["Text","Dissertation"]},"updated_at":"2026-07-27T19:05:09Z"}