{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/15519"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/15519","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Defining a role for the cystic fibrosis transmembrane conductance regulator in the heart","abstract":"While cystic fibrosis (CF) is commonly thought of as a lung disease, since it’s first description 70 years ago we have come to understand that loss of CFTR (cystic fibrosis transmembrane conductance regulator) function affects numerous tissues and systems throughout the body. Concerning the heart, right ventricular dysfunction secondary to pulmonary abnormalities has long been recognized. However, the issue as to whether loss of CFTR function causes primary disturbances in the heart has remained an unsolved and often debated question. Thus, the goal of the research presented herein was to answer two fundamental questions, 1) “Does CFTR play a physiological role in heart function?,” and 2) “What direct impact does loss of CFTR activity have on heart function?” These are particularly timely questions now as CF patients are living longer and the development of CFTR modulators is being pursued with increased vigor. Thus, an understanding if CF patients will be at increased risk for heart disease and whether new therapies may affect heart function are of direct relevance to the care of these individuals. To begin to answer the questions presented we have examined how modulation of CFTR affects neonatal ventricular cardiomyocyte contraction rate. We found that CFTR is involved in the regulation of both baseline and beta-adrenergic stimulated contraction rate. Additionally, loss of CFTR activity, whether acutely or chronically, leads to modulation of intracellular signaling molecules and other Cl- channels, which in some cases can completely compensate for this loss, while in other cases cannot. Finally, in vivo examination of heart function in CFTR KO mice has elucidated disturbances in heart structure and function, which may translate into problems experienced by CF patients. In sum, this work presents a significant expansion of our understanding regarding the role of CFTR in heart function and highlights the need to further pursue a more in-depth analysis of the health of the heart in CF patients.","abstract_html":"While cystic fibrosis (CF) is commonly thought of as a lung disease, since it’s first description 70 years ago we have come to understand that loss of CFTR (cystic fibrosis transmembrane conductance regulator) function affects numerous tissues and systems throughout the body. Concerning the heart, right ventricular dysfunction secondary to pulmonary abnormalities has long been recognized. However, the issue as to whether loss of CFTR function causes primary disturbances in the heart has remained an unsolved and often debated question. Thus, the goal of the research presented herein was to answer two fundamental questions, 1) “Does CFTR play a physiological role in heart function?,” and 2) “What direct impact does loss of CFTR activity have on heart function?” These are particularly timely questions now as CF patients are living longer and the development of CFTR modulators is being pursued with increased vigor. Thus, an understanding if CF patients will be at increased risk for heart disease and whether new therapies may affect heart function are of direct relevance to the care of these individuals. To begin to answer the questions presented we have examined how modulation of CFTR affects neonatal ventricular cardiomyocyte contraction rate. We found that CFTR is involved in the regulation of both baseline and beta-adrenergic stimulated contraction rate. Additionally, loss of CFTR activity, whether acutely or chronically, leads to modulation of intracellular signaling molecules and other Cl- channels, which in some cases can completely compensate for this loss, while in other cases cannot. Finally, in vivo examination of heart function in CFTR KO mice has elucidated disturbances in heart structure and function, which may translate into problems experienced by CF patients. In sum, this work presents a significant expansion of our understanding regarding the role of CFTR in heart function and highlights the need to further pursue a more in-depth analysis of the health of the heart in CF patients.","abstract_has_math":false,"creators":["Sellers, Zachary M."],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Molecular & Integrative Physi","degree_department":null,"school":null,"contributors":["Best, Philip M.","Xiang, Yang","Cox, Charles L.","Nelson, Deborah"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-05-14T20:43:58Z","date_published":"2010-05-14T20:43:58Z","updated_at":"2026-07-22T22:25:08Z","subjects":["cystic fibrosis","Cystic fibrosis transmembrane conductance regulator (CFTR)","cardiac myocyte","heart"],"languages":["en"],"rights":["Copyright 2010 Zachary M. Sellers"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/15519","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Best, Philip M.","Xiang, Yang","Cox, Charles L.","Nelson, Deborah"]},{"key":"dc:creator","label":"Author","values":["Sellers, Zachary M."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2010-05-14T20:43:58Z","2012-05-15T10:00:22Z","2010-05"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Molecular & Integrative Physi"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["cystic fibrosis","Cystic fibrosis transmembrane conductance regulator (CFTR)","cardiac myocyte","heart"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2010 Zachary M. Sellers"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/15519"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["While cystic fibrosis (CF) is commonly thought of as a lung disease, since it’s first description 70 years ago we have come to understand that loss of CFTR (cystic fibrosis transmembrane conductance regulator) function affects numerous tissues and systems throughout the body. Concerning the heart, right ventricular dysfunction secondary to pulmonary abnormalities has long been recognized. However, the issue as to whether loss of CFTR function causes primary disturbances in the heart has remained an unsolved and often debated question. Thus, the goal of the research presented herein was to answer two fundamental questions, 1) “Does CFTR play a physiological role in heart function?,” and 2) “What direct impact does loss of CFTR activity have on heart function?” These are particularly timely questions now as CF patients are living longer and the development of CFTR modulators is being pursued with increased vigor. Thus, an understanding if CF patients will be at increased risk for heart disease and whether new therapies may affect heart function are of direct relevance to the care of these individuals. To begin to answer the questions presented we have examined how modulation of CFTR affects neonatal ventricular cardiomyocyte contraction rate. We found that CFTR is involved in the regulation of both baseline and beta-adrenergic stimulated contraction rate. Additionally, loss of CFTR activity, whether acutely or chronically, leads to modulation of intracellular signaling molecules and other Cl- channels, which in some cases can completely compensate for this loss, while in other cases cannot. Finally, in vivo examination of heart function in CFTR KO mice has elucidated disturbances in heart structure and function, which may translate into problems experienced by CF patients. In sum, this work presents a significant expansion of our understanding regarding the role of CFTR in heart function and highlights the need to further pursue a more in-depth analysis of the health of the heart in CF patients.","Item withdrawn by Mark Zulauf (zulauf@illinois.edu) on 2010-03-29T13:35:04Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 1 Sellers_Zachary.pdf: 4085551 bytes, checksum: d1703656f1b3a06119bb0038823305e1 (MD5)","Made available in DSpace on 2010-05-14T20:43:58Z (GMT). No. of bitstreams: 3 Sellers_Zachary.pdf: 4085551 bytes, checksum: d1703656f1b3a06119bb0038823305e1 (MD5) 1_Sellers_Zachary.pdf: 4175360 bytes, checksum: e5050271a874f88421e3ab9edc94909a (MD5) license.txt: 4064 bytes, checksum: 9189c96916acf9830a7c84af48948c2f (MD5)","Item marked as restricted to the 'Administrator' Group (id=1) by William Ingram (wingram2@illinois.edu) on 2010-05-14T20:45:16Z Item is restricted until 2012-05-14T20:45:13Z","Item reinstated by Sarah Shreeves (sshreeve@illinois.edu) on 2012-05-15T10:00:22Z Item was in collections: University of Illinois Dissertations and Theses (ID: 204) Dissertations and Theses - Molecular and Integrative Physiology (ID: 761) No. of bitstreams: 4 Sellers_Zachary.pdf: 4085551 bytes, checksum: d1703656f1b3a06119bb0038823305e1 (MD5) 1_Sellers_Zachary.pdf: 4175360 bytes, checksum: e5050271a874f88421e3ab9edc94909a (MD5) license.txt: 4064 bytes, checksum: 9189c96916acf9830a7c84af48948c2f (MD5) 1_Sellers_Zachary.pdf.txt: 196712 bytes, checksum: 3b4781ec7f796cf8750315d1e8374fa1 (MD5)","Item released from any restrictions by Sarah Shreeves (sshreeve@illinois.edu) on 2012-05-15T10:00:22Z"]},{"key":"dc:title","label":"Title","values":["Defining a role for the cystic fibrosis transmembrane conductance regulator in the heart"]}]}],"canonical_facts":{"dc:contributor":["Best, Philip M.","Xiang, Yang","Cox, Charles L.","Nelson, Deborah"],"dc:creator":["Sellers, Zachary M."],"dc:date":["2010-05-14T20:43:58Z","2012-05-15T10:00:22Z","2010-05"],"dc:description":["While cystic fibrosis (CF) is commonly thought of as a lung disease, since it’s first description 70 years ago we have come to understand that loss of CFTR (cystic fibrosis transmembrane conductance regulator) function affects numerous tissues and systems throughout the body. Concerning the heart, right ventricular dysfunction secondary to pulmonary abnormalities has long been recognized. However, the issue as to whether loss of CFTR function causes primary disturbances in the heart has remained an unsolved and often debated question. Thus, the goal of the research presented herein was to answer two fundamental questions, 1) “Does CFTR play a physiological role in heart function?,” and 2) “What direct impact does loss of CFTR activity have on heart function?” These are particularly timely questions now as CF patients are living longer and the development of CFTR modulators is being pursued with increased vigor. Thus, an understanding if CF patients will be at increased risk for heart disease and whether new therapies may affect heart function are of direct relevance to the care of these individuals. To begin to answer the questions presented we have examined how modulation of CFTR affects neonatal ventricular cardiomyocyte contraction rate. We found that CFTR is involved in the regulation of both baseline and beta-adrenergic stimulated contraction rate. Additionally, loss of CFTR activity, whether acutely or chronically, leads to modulation of intracellular signaling molecules and other Cl- channels, which in some cases can completely compensate for this loss, while in other cases cannot. Finally, in vivo examination of heart function in CFTR KO mice has elucidated disturbances in heart structure and function, which may translate into problems experienced by CF patients. In sum, this work presents a significant expansion of our understanding regarding the role of CFTR in heart function and highlights the need to further pursue a more in-depth analysis of the health of the heart in CF patients.","Item withdrawn by Mark Zulauf (zulauf@illinois.edu) on 2010-03-29T13:35:04Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 1 Sellers_Zachary.pdf: 4085551 bytes, checksum: d1703656f1b3a06119bb0038823305e1 (MD5)","Made available in DSpace on 2010-05-14T20:43:58Z (GMT). No. of bitstreams: 3 Sellers_Zachary.pdf: 4085551 bytes, checksum: d1703656f1b3a06119bb0038823305e1 (MD5) 1_Sellers_Zachary.pdf: 4175360 bytes, checksum: e5050271a874f88421e3ab9edc94909a (MD5) license.txt: 4064 bytes, checksum: 9189c96916acf9830a7c84af48948c2f (MD5)","Item marked as restricted to the 'Administrator' Group (id=1) by William Ingram (wingram2@illinois.edu) on 2010-05-14T20:45:16Z Item is restricted until 2012-05-14T20:45:13Z","Item reinstated by Sarah Shreeves (sshreeve@illinois.edu) on 2012-05-15T10:00:22Z Item was in collections: University of Illinois Dissertations and Theses (ID: 204) Dissertations and Theses - Molecular and Integrative Physiology (ID: 761) No. of bitstreams: 4 Sellers_Zachary.pdf: 4085551 bytes, checksum: d1703656f1b3a06119bb0038823305e1 (MD5) 1_Sellers_Zachary.pdf: 4175360 bytes, checksum: e5050271a874f88421e3ab9edc94909a (MD5) license.txt: 4064 bytes, checksum: 9189c96916acf9830a7c84af48948c2f (MD5) 1_Sellers_Zachary.pdf.txt: 196712 bytes, checksum: 3b4781ec7f796cf8750315d1e8374fa1 (MD5)","Item released from any restrictions by Sarah Shreeves (sshreeve@illinois.edu) on 2012-05-15T10:00:22Z"],"dc:identifier":["http://hdl.handle.net/2142/15519"],"dc:language":["en"],"dc:rights":["Copyright 2010 Zachary M. Sellers"],"dc:subject":["cystic fibrosis","Cystic fibrosis transmembrane conductance regulator (CFTR)","cardiac myocyte","heart"],"dc:title":["Defining a role for the cystic fibrosis transmembrane conductance regulator in the heart"],"thesis:degree_discipline":["Molecular & Integrative Physi"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:08Z"}