Renal medullary carcinoma (RMC) is a lethal cancer that predominantly affects young individuals with sickle cell trait (SCT). It is not currently understood why RMC only affects certain individuals with SCT. We found that patients with RMC more frequently participated in high-intensity exercise than matched controls. Using mouse models of SCT, we demonstrated the significant increase of renal hypoxia in the right kidney following high- but not moderate-intensity exercise. We also demonstrated in cell culture studies that SMARCB1 is ubiquitinated for proteasome-mediated degradation in hypoxia, and the re-expression of SMARCB1 leads to compromised proliferation in renal cells specifically in the context of hypoxia. Overall, we proposed that the link between SCT and SMARCB1 deficiency observed in RMC is due to renal hypoxia, which promotes the loss of SMARCB1 due to its survival advantage in hypoxia.
","abstract_html":"<p>Renal medullary carcinoma (RMC) is a lethal cancer that predominantly affects young individuals with sickle cell trait (SCT). It is not currently understood why RMC only affects certain individuals with SCT. We found that patients with RMC more frequently participated in high-intensity exercise than matched controls. Using mouse models of SCT, we demonstrated the significant increase of renal hypoxia in the right kidney following high- but not moderate-intensity exercise. We also demonstrated in cell culture studies that SMARCB1 is ubiquitinated for proteasome-mediated degradation in hypoxia, and the re-expression of SMARCB1 leads to compromised proliferation in renal cells specifically in the context of hypoxia. Overall, we proposed that the link between SCT and SMARCB1 deficiency observed in RMC is due to renal hypoxia, which promotes the loss of SMARCB1 due to its survival advantage in hypoxia.</p>","abstract_has_math":false,"creators":["Soeung, Melinda","https://orcid.org/0000-0002-6902-898X
"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation (PhD)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Giulio Draetta, MD, PhD","Giannicola Genovese, MD, PhD","Michelle Barton, PhD"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2021,"date_issued":"2021-08-01T07:00:00Z","date_published":"2021-08-01T07:00:00Z","updated_at":"2026-07-24T05:50:24Z","subjects":["sickle cell trait","hypoxia","SWI/SNF complex","BAF complex","Smarcb1","ubiquitin","renal medullary carcinoma","cancer","high-intensity exercise","Cancer Biology","Cellular and Molecular Physiology","Exercise Physiology","Medicine and Health Sciences","Molecular Genetics"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1123","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Giulio Draetta, MD, PhD","Giannicola Genovese, MD, PhD","Michelle Barton, PhD"]},{"key":"dc:creator","label":"Author","values":["Soeung, Melinda","https://orcid.org/0000-0002-6902-898X
"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2022-08-03T07:00:00Z"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation (PhD)"]},{"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":["sickle cell trait","hypoxia","SWI/SNF complex","BAF complex","Smarcb1","ubiquitin","renal medullary carcinoma","cancer","high-intensity exercise","Cancer Biology","Cellular and Molecular Physiology","Exercise Physiology","Medicine and Health Sciences","Molecular Genetics"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1123"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Renal medullary carcinoma (RMC) is a lethal cancer that predominantly affects young individuals with sickle cell trait (SCT). It is not currently understood why RMC only affects certain individuals with SCT. We found that patients with RMC more frequently participated in high-intensity exercise than matched controls. Using mouse models of SCT, we demonstrated the significant increase of renal hypoxia in the right kidney following high- but not moderate-intensity exercise. We also demonstrated in cell culture studies that SMARCB1 is ubiquitinated for proteasome-mediated degradation in hypoxia, and the re-expression of SMARCB1 leads to compromised proliferation in renal cells specifically in the context of hypoxia. Overall, we proposed that the link between SCT and SMARCB1 deficiency observed in RMC is due to renal hypoxia, which promotes the loss of SMARCB1 due to its survival advantage in hypoxia.
"]},{"key":"dc:title","label":"Title","values":["Understanding The Pathogenesis of Renal Medullary Carcinoma"]}]}],"canonical_facts":{"dc:contributor":["Giulio Draetta, MD, PhD","Giannicola Genovese, MD, PhD","Michelle Barton, PhD"],"dc:creator":["Soeung, Melinda","https://orcid.org/0000-0002-6902-898X
"],"dc:date.available":["2022-08-03T07:00:00Z"],"dc:description.abstract":["Renal medullary carcinoma (RMC) is a lethal cancer that predominantly affects young individuals with sickle cell trait (SCT). It is not currently understood why RMC only affects certain individuals with SCT. We found that patients with RMC more frequently participated in high-intensity exercise than matched controls. Using mouse models of SCT, we demonstrated the significant increase of renal hypoxia in the right kidney following high- but not moderate-intensity exercise. We also demonstrated in cell culture studies that SMARCB1 is ubiquitinated for proteasome-mediated degradation in hypoxia, and the re-expression of SMARCB1 leads to compromised proliferation in renal cells specifically in the context of hypoxia. Overall, we proposed that the link between SCT and SMARCB1 deficiency observed in RMC is due to renal hypoxia, which promotes the loss of SMARCB1 due to its survival advantage in hypoxia.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1123"],"dc:subject":["sickle cell trait","hypoxia","SWI/SNF complex","BAF complex","Smarcb1","ubiquitin","renal medullary carcinoma","cancer","high-intensity exercise","Cancer Biology","Cellular and Molecular Physiology","Exercise Physiology","Medicine and Health Sciences","Molecular Genetics"],"dc:title":["Understanding The Pathogenesis of Renal Medullary Carcinoma"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:50:24Z"}