Myeloproliferative neoplasms (MPNs) are a hematopoietic disease characterized by hyperproliferation of cells of the myeloid lineage for which current therapeutic options are limited. Discovered in 2005, the JAK2V617F mutation is the most common driver mutation in BCR-ABL negative MPNs, resulting in constitutive activation of the JAK2 protein and the JAK-STAT signaling pathway. A role for the methyltransferase activity of Protein Arginine Methyltransferase 5 (PRMT5) has been proposed in JAK2-mutant MPN, highlighting both a mechanism through which this mutation can drive disease progression and a potential mode of therapeutic intervention. Staphylococcal Nuclease Domain-Containing Protein 1 (SND1) is the effector molecule responsible for reading the symmetric dimethyl-arginine (SDMA) marks deposited by PRMT5, underpinning a potential critical role in MPN pathogenesis and treatment. SND1 is the only human protein known to contain the Staphylococcal nuclease-like domain, making it a uniquely promising therapeutic target for which there is little potential for off-site effects by small molecule inhibition. Using a human JAK2V617F-mutant MPN cell line as a disease model, we are actively exploring the roles of PRMT5 and SND1 in the progression of this class of diseases. We are establishing the effects that reduced or abolished PRMT5/SND1 activity have on cell fitness by generating genetically modified cell lines and utilizing small molecule inhibitors. Both SND1 and PRMT5 show promise in altering the proliferation and differentiation patterns of JAK2-mutant MPN cells, encouraging further investigation into their potential as therapeutic targets in the treatment of these diseases.
","abstract_html":"<p>Myeloproliferative neoplasms (MPNs) are a hematopoietic disease characterized by hyperproliferation of cells of the myeloid lineage for which current therapeutic options are limited. Discovered in 2005, the JAK2V617F mutation is the most common driver mutation in BCR-ABL negative MPNs, resulting in constitutive activation of the JAK2 protein and the JAK-STAT signaling pathway. A role for the methyltransferase activity of Protein Arginine Methyltransferase 5 (PRMT5) has been proposed in JAK2-mutant MPN, highlighting both a mechanism through which this mutation can drive disease progression and a potential mode of therapeutic intervention. Staphylococcal Nuclease Domain-Containing Protein 1 (SND1) is the effector molecule responsible for reading the symmetric dimethyl-arginine (SDMA) marks deposited by PRMT5, underpinning a potential critical role in MPN pathogenesis and treatment. SND1 is the only human protein known to contain the Staphylococcal nuclease-like domain, making it a uniquely promising therapeutic target for which there is little potential for off-site effects by small molecule inhibition. Using a human JAK2V617F-mutant MPN cell line as a disease model, we are actively exploring the roles of PRMT5 and SND1 in the progression of this class of diseases. We are establishing the effects that reduced or abolished PRMT5/SND1 activity have on cell fitness by generating genetically modified cell lines and utilizing small molecule inhibitors. Both SND1 and PRMT5 show promise in altering the proliferation and differentiation patterns of JAK2-mutant MPN cells, encouraging further investigation into their potential as therapeutic targets in the treatment of these diseases.</p>","abstract_has_math":false,"creators":["Rubiano, Rocio","0009-0002-8656-3869
"],"institution":null,"degree_name":"Masters of Science (MS)","degree_level":"Thesis (MS)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Margarida Santos, PhD","Mark T. Bedford, PhD","Xiaodong Cheng, PhD"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-08-01T07:00:00Z","date_published":"2024-08-01T07:00:00Z","updated_at":"2026-07-24T05:49:08Z","subjects":["PRMT5","SND1","JAK2","myeloproliferative neoplasms","Biology","Hemic and Lymphatic Diseases","Neoplasms","Other Genetics and Genomics"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1382","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Margarida Santos, PhD","Mark T. Bedford, PhD","Xiaodong Cheng, PhD"]},{"key":"dc:creator","label":"Author","values":["Rubiano, Rocio","0009-0002-8656-3869
"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2025-08-08T07:00:00Z"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis (MS)"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Masters of Science (MS)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["PRMT5","SND1","JAK2","myeloproliferative neoplasms","Biology","Hemic and Lymphatic Diseases","Neoplasms","Other Genetics and Genomics"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1382"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Myeloproliferative neoplasms (MPNs) are a hematopoietic disease characterized by hyperproliferation of cells of the myeloid lineage for which current therapeutic options are limited. Discovered in 2005, the JAK2V617F mutation is the most common driver mutation in BCR-ABL negative MPNs, resulting in constitutive activation of the JAK2 protein and the JAK-STAT signaling pathway. A role for the methyltransferase activity of Protein Arginine Methyltransferase 5 (PRMT5) has been proposed in JAK2-mutant MPN, highlighting both a mechanism through which this mutation can drive disease progression and a potential mode of therapeutic intervention. Staphylococcal Nuclease Domain-Containing Protein 1 (SND1) is the effector molecule responsible for reading the symmetric dimethyl-arginine (SDMA) marks deposited by PRMT5, underpinning a potential critical role in MPN pathogenesis and treatment. SND1 is the only human protein known to contain the Staphylococcal nuclease-like domain, making it a uniquely promising therapeutic target for which there is little potential for off-site effects by small molecule inhibition. Using a human JAK2V617F-mutant MPN cell line as a disease model, we are actively exploring the roles of PRMT5 and SND1 in the progression of this class of diseases. We are establishing the effects that reduced or abolished PRMT5/SND1 activity have on cell fitness by generating genetically modified cell lines and utilizing small molecule inhibitors. Both SND1 and PRMT5 show promise in altering the proliferation and differentiation patterns of JAK2-mutant MPN cells, encouraging further investigation into their potential as therapeutic targets in the treatment of these diseases.
"]},{"key":"dc:title","label":"Title","values":["Exploring the role of the arginine-methylation writer-reader pair PRMT5/SND1 in JAK2-mutant myeloproliferative neoplasms"]}]}],"canonical_facts":{"dc:contributor":["Margarida Santos, PhD","Mark T. Bedford, PhD","Xiaodong Cheng, PhD"],"dc:creator":["Rubiano, Rocio","0009-0002-8656-3869
"],"dc:date.available":["2025-08-08T07:00:00Z"],"dc:description.abstract":["Myeloproliferative neoplasms (MPNs) are a hematopoietic disease characterized by hyperproliferation of cells of the myeloid lineage for which current therapeutic options are limited. Discovered in 2005, the JAK2V617F mutation is the most common driver mutation in BCR-ABL negative MPNs, resulting in constitutive activation of the JAK2 protein and the JAK-STAT signaling pathway. A role for the methyltransferase activity of Protein Arginine Methyltransferase 5 (PRMT5) has been proposed in JAK2-mutant MPN, highlighting both a mechanism through which this mutation can drive disease progression and a potential mode of therapeutic intervention. Staphylococcal Nuclease Domain-Containing Protein 1 (SND1) is the effector molecule responsible for reading the symmetric dimethyl-arginine (SDMA) marks deposited by PRMT5, underpinning a potential critical role in MPN pathogenesis and treatment. SND1 is the only human protein known to contain the Staphylococcal nuclease-like domain, making it a uniquely promising therapeutic target for which there is little potential for off-site effects by small molecule inhibition. Using a human JAK2V617F-mutant MPN cell line as a disease model, we are actively exploring the roles of PRMT5 and SND1 in the progression of this class of diseases. We are establishing the effects that reduced or abolished PRMT5/SND1 activity have on cell fitness by generating genetically modified cell lines and utilizing small molecule inhibitors. Both SND1 and PRMT5 show promise in altering the proliferation and differentiation patterns of JAK2-mutant MPN cells, encouraging further investigation into their potential as therapeutic targets in the treatment of these diseases.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1382"],"dc:subject":["PRMT5","SND1","JAK2","myeloproliferative neoplasms","Biology","Hemic and Lymphatic Diseases","Neoplasms","Other Genetics and Genomics"],"dc:title":["Exploring the role of the arginine-methylation writer-reader pair PRMT5/SND1 in JAK2-mutant myeloproliferative neoplasms"],"thesis:degree_level":["Thesis (MS)"],"thesis:degree_name":["Masters of Science (MS)"]},"updated_at":"2026-07-24T05:49:08Z"}