{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/10587"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/10587","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"The Role of DnaJC7 in Modulating Tau Aggregation in the Cell","abstract":"Appendix A contains a previously published manuscript, which is referenced below as a related citation.","abstract_html":"Appendix A contains a previously published manuscript, which is referenced below as a related citation.","abstract_has_math":false,"creators":["Perez, Valerie Ann"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Rice, Luke M.","Diamond, Marc","Joachimiak, Lukasz","Chook, Yuh Min","Woodruff, Jeffrey B."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-06-03T19:48:39Z","date_published":"2025-06-03T19:48:39Z","updated_at":"2026-07-24T05:52:17Z","subjects":["Molecular Chaperones","tau Proteins","Tauopathies","Amyloid"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["Hou, Z., Wydorski, P. M., Perez, V. A., Mendoza-Oliva, A., Ryder, B. D., Mirbaha, H., Kashmer, O., & Joachimiak, L. A. (2021). DnaJC7 binds natively folded structural elements in tau to inhibit amyloid formation. Nature communications, 12(1), 5338. https://doi.org/10.1038/s41467-021-25635-y","1522122310"],"render_values":[{"text":"Hou, Z., Wydorski, P. M., Perez, V. A., Mendoza-Oliva, A., Ryder, B. D., Mirbaha, H., Kashmer, O., & Joachimiak, L. A. (2021). DnaJC7 binds natively folded structural elements in tau to inhibit amyloid formation. Nature communications, 12(1), 5338. https://doi.org/10.1038/s41467-021-25635-y","href":"https://doi.org/10.1038/s41467-021-25635-y","code":true},{"text":"1522122310","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/10587","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Rice, Luke M.","Diamond, Marc","Joachimiak, Lukasz","Chook, Yuh Min","Woodruff, Jeffrey B."]},{"key":"dc:creator","label":"Author","values":["Perez, Valerie Ann"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-06-03T19:48:39Z","2023-05","May 2023"]},{"key":"dc:relation","label":"Dc Relation","values":["https://doi.org/10.1038/s41467-021-25635-y"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Molecular Chaperones","tau Proteins","Tauopathies","Amyloid"]}]},{"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":["Hou, Z., Wydorski, P. M., Perez, V. A., Mendoza-Oliva, A., Ryder, B. D., Mirbaha, H., Kashmer, O., & Joachimiak, L. A. (2021). DnaJC7 binds natively folded structural elements in tau to inhibit amyloid formation. Nature communications, 12(1), 5338. https://doi.org/10.1038/s41467-021-25635-y","https://hdl.handle.net/2152.5/10587","1522122310"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Appendix A contains a previously published manuscript, which is referenced below as a related citation.","Tauopathies are a diverse group of neurodegenerative diseases characterized by the abnormal accumulation of misfolded tau protein. The most recognized tauopathy, Alzheimer's Disease, is estimated to affect more than 30 million people worldwide. Mutations that increase the propensity for tau to adopt an aggregation-prone conformation have been identified in familial forms of tauopathies, further emphasizing the causal role of tau misfolding in these neurodegenerative diseases. The Diamond Lab has pioneered the prion model as a hypothesis for how tau can template, or seed, its misfolded conformation onto inert tau protein, thus enabling further aggregation. However, the fate of these aggregates and the key players that may interact with them after they have formed remains poorly understood. We reveal that DnaJC7, a co-chaperone of the J domain protein (JDP) family, engages with tau aggregates and is involved in their clearance from the cell. Additionally, I conducted a genetic screen to knockout all JDPs in our tau biosensor cells to show that DnaJC7 and DnaJB6 are unique in their ability to mitigate tau aggregation in the cell. Further, I show that DnaJC7 KO leads to increased seeding of multiple tau seed sources in the biosensor cells, suggesting that DnaJC7 may serve to protect the endogenous inert tau, in agreement with our previous work showing that DnaJC7 preferentially binds inert monomeric tau over seeding-competent tau. I also surveyed the effects of recently identified ALS-associated mutations in DnaJC7 on intracellular tau seeding to show that five of these mutations increase tau seeding. Surprisingly, the T341P mutant shifts the tau seeding profile to resemble that of a mutant unable to stimulate Hsp70 substrate binding, providing insights into the pathogenic mechanism of this mutation. The work presented here underscores the specific role that DnaJC7 plays in modulating tau aggregation in the cell. Further characterization of the DnaJC7:tau interaction may reveal novel preventative and therapeutic strategies for several neurodegenerative diseases."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["The Role of DnaJC7 in Modulating Tau Aggregation in the Cell"]}]}],"canonical_facts":{"dc:contributor":["Rice, Luke M.","Diamond, Marc","Joachimiak, Lukasz","Chook, Yuh Min","Woodruff, Jeffrey B."],"dc:creator":["Perez, Valerie Ann"],"dc:date":["2025-06-03T19:48:39Z","2023-05","May 2023"],"dc:description":["Appendix A contains a previously published manuscript, which is referenced below as a related citation.","Tauopathies are a diverse group of neurodegenerative diseases characterized by the abnormal accumulation of misfolded tau protein. The most recognized tauopathy, Alzheimer's Disease, is estimated to affect more than 30 million people worldwide. Mutations that increase the propensity for tau to adopt an aggregation-prone conformation have been identified in familial forms of tauopathies, further emphasizing the causal role of tau misfolding in these neurodegenerative diseases. The Diamond Lab has pioneered the prion model as a hypothesis for how tau can template, or seed, its misfolded conformation onto inert tau protein, thus enabling further aggregation. However, the fate of these aggregates and the key players that may interact with them after they have formed remains poorly understood. We reveal that DnaJC7, a co-chaperone of the J domain protein (JDP) family, engages with tau aggregates and is involved in their clearance from the cell. Additionally, I conducted a genetic screen to knockout all JDPs in our tau biosensor cells to show that DnaJC7 and DnaJB6 are unique in their ability to mitigate tau aggregation in the cell. Further, I show that DnaJC7 KO leads to increased seeding of multiple tau seed sources in the biosensor cells, suggesting that DnaJC7 may serve to protect the endogenous inert tau, in agreement with our previous work showing that DnaJC7 preferentially binds inert monomeric tau over seeding-competent tau. I also surveyed the effects of recently identified ALS-associated mutations in DnaJC7 on intracellular tau seeding to show that five of these mutations increase tau seeding. Surprisingly, the T341P mutant shifts the tau seeding profile to resemble that of a mutant unable to stimulate Hsp70 substrate binding, providing insights into the pathogenic mechanism of this mutation. The work presented here underscores the specific role that DnaJC7 plays in modulating tau aggregation in the cell. Further characterization of the DnaJC7:tau interaction may reveal novel preventative and therapeutic strategies for several neurodegenerative diseases."],"dc:format":["application/pdf"],"dc:identifier":["Hou, Z., Wydorski, P. M., Perez, V. A., Mendoza-Oliva, A., Ryder, B. D., Mirbaha, H., Kashmer, O., & Joachimiak, L. A. (2021). DnaJC7 binds natively folded structural elements in tau to inhibit amyloid formation. Nature communications, 12(1), 5338. https://doi.org/10.1038/s41467-021-25635-y","https://hdl.handle.net/2152.5/10587","1522122310"],"dc:language":["en"],"dc:relation":["https://doi.org/10.1038/s41467-021-25635-y"],"dc:subject":["Molecular Chaperones","tau Proteins","Tauopathies","Amyloid"],"dc:title":["The Role of DnaJC7 in Modulating Tau Aggregation in the Cell"],"dc:type":["Thesis","text"]},"updated_at":"2026-07-24T05:52:17Z"}