{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/10633"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/10633","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"Mitochondrial Metabolism of Human Kidney Cancers","abstract":"The general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.","abstract_html":"The general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.","abstract_has_math":false,"creators":["Bezwada, Divya"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Morrison, Sean J.","DeBerardinis, Ralph J.","Malloy, Craig R.","Nijhawan, Deepak"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-06-03T19:58:43Z","date_published":"2025-06-03T19:58:43Z","updated_at":"2026-07-24T05:52:17Z","subjects":["Kidney Neoplasms","Mitochondria","Neoplasm Metastasis","Electron Transport Complex I"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["1522122337"],"render_values":[{"text":"1522122337","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/10633","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Morrison, Sean J.","DeBerardinis, Ralph J.","Malloy, Craig R.","Nijhawan, Deepak"]},{"key":"dc:creator","label":"Author","values":["Bezwada, Divya"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-06-03T19:58:43Z","2023-05","May 2023"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Kidney Neoplasms","Mitochondria","Neoplasm Metastasis","Electron Transport Complex I"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/10633","1522122337"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.","Metabolism is often dysregulated in cancer. Pinpointing the exact metabolic requirements critical for cancer cell survival has been the subject of intense study for the last 100 years. However, very few metabolic targets have successfully translated to effective therapies for patients. Progress in clinical translation has been limited as the vast majority of cancer metabolism studies are currently conducted in preclinical models of cell culture and mice. How relevant these preclinical studies are to disease biology in humans is almost entirely unknown. I use a multidisciplinary approach to infuse 13C-labeled nutrients during surgical tumor resection in over 80 patients with kidney cancer. Labeling from [U-13C]glucose varies across cancer subtypes, indicating that the kidney environment alone cannot account for all metabolic reprogramming in these tumors. Compared to the adjacent kidney, clear cell renal cell carcinomas (ccRCC) display suppressed labelling of tricarboxylic acid (TCA) cycle intermediates in vivo and in organotypic slices cultured ex vivo, indicating that suppressed labeling is tissue intrinsic. Infusions of [1,2-13C]acetate and [U-13C]glutamine in patients, coupled with respiratory flux of mitochondria isolated from kidney and tumor tissue, reveal primary defects in mitochondrial function in human ccRCC. However, ccRCC metastases unexpectedly have enhanced labeling of TCA cycle intermediates compared to primary ccRCCs, indicating a divergent metabolic program during ccRCC metastasis in patients. In mice, stimulating respiration in ccRCC cells is sufficient to promote metastatic colonization. Altogether, these findings indicate that metabolic properties evolve during human kidney cancer progression, and suggest that mitochondrial respiration may be limiting for ccRCC metastasis but not for ccRCC growth at the site of origin."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Mitochondrial Metabolism of Human Kidney Cancers"]}]}],"canonical_facts":{"dc:contributor":["Morrison, Sean J.","DeBerardinis, Ralph J.","Malloy, Craig R.","Nijhawan, Deepak"],"dc:creator":["Bezwada, Divya"],"dc:date":["2025-06-03T19:58:43Z","2023-05","May 2023"],"dc:description":["The general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.","Metabolism is often dysregulated in cancer. Pinpointing the exact metabolic requirements critical for cancer cell survival has been the subject of intense study for the last 100 years. However, very few metabolic targets have successfully translated to effective therapies for patients. Progress in clinical translation has been limited as the vast majority of cancer metabolism studies are currently conducted in preclinical models of cell culture and mice. How relevant these preclinical studies are to disease biology in humans is almost entirely unknown. I use a multidisciplinary approach to infuse 13C-labeled nutrients during surgical tumor resection in over 80 patients with kidney cancer. Labeling from [U-13C]glucose varies across cancer subtypes, indicating that the kidney environment alone cannot account for all metabolic reprogramming in these tumors. Compared to the adjacent kidney, clear cell renal cell carcinomas (ccRCC) display suppressed labelling of tricarboxylic acid (TCA) cycle intermediates in vivo and in organotypic slices cultured ex vivo, indicating that suppressed labeling is tissue intrinsic. Infusions of [1,2-13C]acetate and [U-13C]glutamine in patients, coupled with respiratory flux of mitochondria isolated from kidney and tumor tissue, reveal primary defects in mitochondrial function in human ccRCC. However, ccRCC metastases unexpectedly have enhanced labeling of TCA cycle intermediates compared to primary ccRCCs, indicating a divergent metabolic program during ccRCC metastasis in patients. In mice, stimulating respiration in ccRCC cells is sufficient to promote metastatic colonization. Altogether, these findings indicate that metabolic properties evolve during human kidney cancer progression, and suggest that mitochondrial respiration may be limiting for ccRCC metastasis but not for ccRCC growth at the site of origin."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2152.5/10633","1522122337"],"dc:language":["en"],"dc:subject":["Kidney Neoplasms","Mitochondria","Neoplasm Metastasis","Electron Transport Complex I"],"dc:title":["Mitochondrial Metabolism of Human Kidney Cancers"],"dc:type":["Thesis","text"]},"updated_at":"2026-07-24T05:52:17Z"}