{"id":972,"date":"2021-06-15T11:26:33","date_gmt":"2021-06-15T15:26:33","guid":{"rendered":"https:\/\/scienceweb.clemson.edu\/chg\/?p=972"},"modified":"2025-12-04T15:53:51","modified_gmt":"2025-12-04T20:53:51","slug":"dr-heather-flanagan-steet","status":"publish","type":"post","link":"https:\/\/scienceweb.clemson.edu\/ihg\/dr-heather-flanagan-steet\/","title":{"rendered":"Dr. Heather Flanagan-Steet"},"content":{"rendered":"

[et_pb_section fb_built=”1″ admin_label=”section” _builder_version=”4.16″ global_colors_info=”{}”][et_pb_row admin_label=”row” _builder_version=”4.16″ background_size=”initial” background_position=”top_left” background_repeat=”repeat” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”Text” _builder_version=”4.27.4″ background_size=”initial” background_position=”top_left” background_repeat=”repeat” hover_enabled=”0″ global_colors_info=”{}” sticky_enabled=”0″]<\/p>\n

Director of Functional Studies, Greenwood Genetic Center<\/strong><\/p>\n

Email: heatherfs@ggc.org<\/p>\n

Biosketch\"heather<\/strong><\/h2>\n

Dr. Flanagan-Steet\u2019s scientific training started with a B.A. in Biology from Carleton College (Northfield, MN). In 2001 she received her PhD in Molecular, Cellular, and Developmental Biology from the University of Colorado, Boulder. From there she pursued post-doctoral studies in neurobiology with Dr. Joshua Sanes at Washington University in St. Louis. During her post-doctoral training Dr. Flanagan-Steet pioneered the use of zebrafish to model rare genetic disorders. This effort seeded a long-term collaboration with her husband, Dr. Richard Steet. She began her independent career at the University of Georgia, where she established multiple models and methods to uncover pathogenic mechanisms of both lysosomal storage disorders and congenital disorders of glycosylation.\u00a0 In 2018 after 12 productive years at the University of Georgia, Dr. Flanagan-Steet and her zebrafish relocated to the Greenwood Genetic Center (GGC). \u00a0At the GGC Dr. Flanagan-Steet serves Director of Functional Studies. In this role she works closely with the Center\u2019s tremendous team to advance our understanding of genetic disorders. In parallel she continues to pursue pathogenic mechanisms driving disease.<\/p>\n

Research<\/strong><\/h3>\n

Dr. Flanagan-Steet\u2019s research has largely focused on defining the mechanisms governing early tissue development. This has ranged from investigating how neuromuscular synapses form to development of the embryonic heart and craniofacial skeleton. For nearly two decades Dr. Flanagan-Steet\u2019s efforts have centered on defining the molecular and cellular mechanisms underlying pathogenesis of rare genetic diseases, including several lysosomal storage disorders and the congenital disorders of glycosylation. Her work on genetic diseases has primarily involved generating zebrafish models to investigate gene function and disease pathogenesis. Her work pioneered the use of zebrafish to model rare inherited diseases, bringing new insight into the molecular initiators and mechanisms underlying pathogenesis of the lysosomal storage disorder mucolipidosis II. The success of these studies has been augmented by her long time collaboration with her colleague and spouse, Dr. Richard Steet.<\/p>\n

Recent Publications<\/strong><\/h3>\n

Yu SH, Wang T, Wiggins K, Louie RJ, Merino EF, Skinner C, Cassera MB, Meagher K, Goldberg P, Rismanchi N, Chen D, Lyons MJ, Flanagan-Steet H<\/strong>, Steet R.\u00a0Lysosomal cholesterol accumulation contributes to the movement phenotypes associated with NUS1 haploinsufficiency.\u00a0<\/a>Genet Med.\u00a02021 Mar 17;.\u00a0doi: 10.1038\/s41436-021-01137-6.\u00a0[Epub ahead of print]\u00a0PubMed PMID: 33731878.<\/p>\n

Lu PN, Moreland T, Christian CJ, Lund TC, Steet RA, Flanagan-Steet H<\/strong>.\u00a0Inappropriate cathepsin K secretion promotes its enzymatic activation driving heart and valve malformation.\u00a0<\/a>JCI Insight.\u00a02020 Oct 15;5(20).\u00a0doi: 10.1172\/jci.insight.133019.\u00a0PubMed PMID: 33055423; PubMed Central PMCID: PMC7605527.<\/p>\n

Yu SH, Pollard L, Wood T, Flanagan-Steet H<\/strong>, Steet R.\u00a0A Biochemical Platform to Define the Relative Specific Activity of\u00a0IDUA<\/em>\u00a0Variants Identified by Newborn Screening.\u00a0<\/a>Int J Neonatal Screen.\u00a02020 Nov 12;6(4).\u00a0doi: 10.3390\/ijns6040088.\u00a0PubMed PMID: 33198351; PubMed Central PMCID: PMC7711455.<\/p>\n

Cristofoli F, Moss T, Moore HW, Devriendt K, Flanagan-Steet H<\/strong>, May M, Jones J, Roelens F, Fons C, Fernandez A, Martorell L, Selicorni A, Maitz S, Vitiello G, Van der Hoeven G, Skinner SA, Bollen M, Vermeesch JR, Steet R, Van Esch H.\u00a0De Novo Variants in LMNB1 Cause Pronounced Syndromic Microcephaly and Disruption of Nuclear Envelope Integrity.\u00a0<\/a>Am J Hum Genet.\u00a02020 Oct 1;107(4):753-762.\u00a0doi: 10.1016\/j.ajhg.2020.08.015.\u00a0Epub 2020 Sep 9.\u00a0PubMed PMID: 32910914; PubMed Central PMCID: PMC7536573.<\/p>\n

Naumchik BM, Gupta A, Flanagan-Steet H<\/strong>, Steet RA, Cathey SS, Orchard PJ, Lund TC.\u00a0The Role of Hematopoietic Cell Transplant in the Glycoprotein Diseases.\u00a0<\/a>Cells.\u00a02020 Jun 5;9(6).\u00a0doi: 10.3390\/cells9061411.\u00a0Review.\u00a0PubMed PMID: 32517081; PubMed Central PMCID: PMC7348849.<\/p>\n

Ates KM, Wang T, Moreland T, Veeranan-Karmegam R, Ma M, Jeter C, Anand P, Wenzel W, Kim HG, Wolfe LA, Stephen J, Adams DR, Markello T, Tifft CJ, Settlage R, Gahl WA, Gonsalvez GB, Malicdan MC, Flanagan-Steet H<\/strong>, Pan YA.\u00a0Deficiency in the endocytic adaptor proteins PHETA1\/2 impairs renal and craniofacial development.\u00a0<\/a>Dis Model Mech.\u00a02020 May 26;13(5).\u00a0doi: 10.1242\/dmm.041913.\u00a0PubMed PMID: 32152089; PubMed Central PMCID: PMC7272357.<\/p>\n

Barnes JW, Aarnio-Peterson M, Norris J, Haskins M, Flanagan-Steet H<\/strong>, Steet R.\u00a0Upregulation of Sortilin, a Lysosomal Sorting Receptor, Corresponds with Reduced Bioavailability of Latent TGF\u03b2 in Mucolipidosis II Cells.\u00a0<\/a>Biomolecules.\u00a02020 Apr 26;10(5).\u00a0doi: 10.3390\/biom10050670.\u00a0PubMed PMID: 32357547; PubMed Central PMCID: PMC7277838.<\/p>\n

Klaver E, Zhao P, May M, Flanagan-Steet H<\/strong>, Freeze HH, Gilmore R, Wells L, Contessa J, Steet R.\u00a0Selective inhibition of N-linked glycosylation impairs receptor tyrosine kinase processing.\u00a0<\/a>Dis Model Mech.\u00a02019 Jun 5;12(6).\u00a0doi: 10.1242\/dmm.039602.\u00a0PubMed PMID: 31101650; PubMed Central PMCID: PMC6602306.<\/p>\n

Flanagan-Steet H<\/strong>, Christian C, Lu PN, Aarnio-Peterson M, Sanman L, Archer-Hartmann S, Azadi P, Bogyo M, Steet RA.\u00a0TGF-\u00df Regulates Cathepsin Activation during Normal and Pathogenic Development.\u00a0<\/a>Cell Rep.\u00a02018 Mar 13;22(11):2964-2977.\u00a0doi: 10.1016\/j.celrep.2018.02.066.\u00a0PubMed PMID: 29539424; PubMed Central PMCID: PMC6247414.<\/p>\n

Aarnio-Peterson M, Zhao P, Yu SH, Christian C, Flanagan-Steet H<\/strong>, Wells L, Steet R.\u00a0Altered Met receptor phosphorylation and LRP1-mediated uptake in cells lacking carbohydrate-dependent lysosomal targeting.\u00a0<\/a>J Biol Chem.\u00a02017 Sep 8;292(36):15094-15104.\u00a0doi: 10.1074\/jbc.M117.790139.\u00a0Epub 2017 Jul 19.\u00a0PubMed PMID: 28724630; PubMed Central PMCID: PMC5592684.<\/p>\n

Flanagan-Steet H<\/strong>, Matheny C, Petrey A, Parker J, Steet R.\u00a0Enzyme-specific differences in mannose phosphorylation between GlcNAc-1-phosphotransferase \u03b1\u03b2 and \u03b3 subunit deficient zebrafish support cathepsin proteases as early mediators of mucolipidosis pathology.\u00a0<\/a>Biochim Biophys Acta.\u00a02016 Sep;1860(9):1845-53.\u00a0doi: 10.1016\/j.bbagen.2016.05.029.\u00a0Epub 2016 May 27.\u00a0PubMed PMID: 27241848; PubMed Central PMCID: PMC4949139.<\/p>\n

Flanagan-Steet H, Aarnio M, Kwan B, Guihard P, Petrey A, Haskins M, Blanchard F, Steet R<\/strong>.\u00a0Cathepsin-Mediated Alterations in TGF\u00df-Related Signaling Underlie Disrupted Cartilage and Bone Maturation Associated With Impaired Lysosomal Targeting.\u00a0<\/a>J Bone Miner Res.\u00a02016 Mar;31(3):535-48.\u00a0doi: 10.1002\/jbmr.2722.\u00a0Epub 2015 Oct 13.\u00a0PubMed PMID: 26404503; PubMed Central PMCID: PMC4808492.<\/p>\n

[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/p>\n","protected":false},"excerpt":{"rendered":"

Director of Functional Studies, Greenwood Genetic Center Email: heatherfs@ggc.org Biosketch Dr. Flanagan-Steet\u2019s scientific training started with a B.A. in Biology from Carleton College (Northfield, MN). In 2001 she received her PhD in Molecular, Cellular, and Developmental Biology from the University of Colorado, Boulder. From there she pursued post-doctoral studies in neurobiology with Dr. Joshua Sanes […]<\/p>\n","protected":false},"author":13,"featured_media":973,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"Director of Functional Studies, Greenwood Genetic Center<\/strong>\r\n\r\nEmail: heatherfs@ggc.org\r\n\r\nPhone: 864-388-1806\r\n

Biosketch\"heather<\/strong><\/h3>\r\nDr. Flanagan-Steet\u2019s scientific training started with a B.A. in Biology from Carleton College (Northfield, MN). In 2001 she received her PhD in Molecular, Cellular, and Developmental Biology from the University of Colorado, Boulder. From there she pursued post-doctoral studies in neurobiology with Dr. Joshua Sanes at Washington University in St. Louis. During her post-doctoral training Dr. Flanagan-Steet pioneered the use of zebrafish to model rare genetic disorders. This effort seeded a long-term collaboration with her husband, Dr. Richard Steet. She began her independent career at the University of Georgia, where she established multiple models and methods to uncover pathogenic mechanisms of both lysosomal storage disorders and congenital disorders of glycosylation.\u00a0 In 2018 after 12 productive years at the University of Georgia, Dr. Flanagan-Steet and her zebrafish relocated to the Greenwood Genetic Center (GGC). \u00a0At the GGC Dr. Flanagan-Steet serves Director of Functional Studies. In this role she works closely with the Center\u2019s tremendous team to advance our understanding of genetic disorders. In parallel she continues to pursue pathogenic mechanisms driving disease.\r\n

Research<\/strong><\/h3>\r\nDr. Flanagan-Steet\u2019s research has largely focused on defining the mechanisms governing early tissue development. This has ranged from investigating how neuromuscular synapses form to development of the embryonic heart and craniofacial skeleton. For nearly two decades Dr. Flanagan-Steet\u2019s efforts have centered on defining the molecular and cellular mechanisms underlying pathogenesis of rare genetic diseases, including several lysosomal storage disorders and the congenital disorders of glycosylation. Her work on genetic diseases has primarily involved generating zebrafish models to investigate gene function and disease pathogenesis. Her work pioneered the use of zebrafish to model rare inherited diseases, bringing new insight into the molecular initiators and mechanisms underlying pathogenesis of the lysosomal storage disorder mucolipidosis II. The success of these studies has been augmented by her long time collaboration with her colleague and spouse, Dr. Richard Steet.\r\n

Recent Publications<\/strong><\/h3>\r\nYu SH, Wang T, Wiggins K, Louie RJ, Merino EF, Skinner C, Cassera MB, Meagher K, Goldberg P, Rismanchi N, Chen D, Lyons MJ, Flanagan-Steet H<\/strong>, Steet R.\u00a0Lysosomal cholesterol accumulation contributes to the movement phenotypes associated with NUS1 haploinsufficiency.\u00a0<\/a>Genet Med.\u00a02021 Mar 17;.\u00a0doi: 10.1038\/s41436-021-01137-6.\u00a0[Epub ahead of print]\u00a0PubMed PMID: 33731878.\r\n\r\nLu PN, Moreland T, Christian CJ, Lund TC, Steet RA, Flanagan-Steet H<\/strong>.\u00a0Inappropriate cathepsin K secretion promotes its enzymatic activation driving heart and valve malformation.\u00a0<\/a>JCI Insight.\u00a02020 Oct 15;5(20).\u00a0doi: 10.1172\/jci.insight.133019.\u00a0PubMed PMID: 33055423; PubMed Central PMCID: PMC7605527.\r\n\r\nYu SH, Pollard L, Wood T, Flanagan-Steet H<\/strong>, Steet R.\u00a0A Biochemical Platform to Define the Relative Specific Activity of\u00a0IDUA<\/em>\u00a0Variants Identified by Newborn Screening.\u00a0<\/a>Int J Neonatal Screen.\u00a02020 Nov 12;6(4).\u00a0doi: 10.3390\/ijns6040088.\u00a0PubMed PMID: 33198351; PubMed Central PMCID: PMC7711455.\r\n\r\nCristofoli F, Moss T, Moore HW, Devriendt K, Flanagan-Steet H<\/strong>, May M, Jones J, Roelens F, Fons C, Fernandez A, Martorell L, Selicorni A, Maitz S, Vitiello G, Van der Hoeven G, Skinner SA, Bollen M, Vermeesch JR, Steet R, Van Esch H.\u00a0De Novo Variants in LMNB1 Cause Pronounced Syndromic Microcephaly and Disruption of Nuclear Envelope Integrity.\u00a0<\/a>Am J Hum Genet.\u00a02020 Oct 1;107(4):753-762.\u00a0doi: 10.1016\/j.ajhg.2020.08.015.\u00a0Epub 2020 Sep 9.\u00a0PubMed PMID: 32910914; PubMed Central PMCID: PMC7536573.\r\n\r\nNaumchik BM, Gupta A, Flanagan-Steet H<\/strong>, Steet RA, Cathey SS, Orchard PJ, Lund TC.\u00a0The Role of Hematopoietic Cell Transplant in the Glycoprotein Diseases.\u00a0<\/a>Cells.\u00a02020 Jun 5;9(6).\u00a0doi: 10.3390\/cells9061411.\u00a0Review.\u00a0PubMed PMID: 32517081; PubMed Central PMCID: PMC7348849.\r\n\r\nAtes KM, Wang T, Moreland T, Veeranan-Karmegam R, Ma M, Jeter C, Anand P, Wenzel W, Kim HG, Wolfe LA, Stephen J, Adams DR, Markello T, Tifft CJ, Settlage R, Gahl WA, Gonsalvez GB, Malicdan MC, Flanagan-Steet H<\/strong>, Pan YA.\u00a0Deficiency in the endocytic adaptor proteins PHETA1\/2 impairs renal and craniofacial development.\u00a0<\/a>Dis Model Mech.\u00a02020 May 26;13(5).\u00a0doi: 10.1242\/dmm.041913.\u00a0PubMed PMID: 32152089; PubMed Central PMCID: PMC7272357.\r\n\r\nBarnes JW, Aarnio-Peterson M, Norris J, Haskins M, Flanagan-Steet H<\/strong>, Steet R.\u00a0Upregulation of Sortilin, a Lysosomal Sorting Receptor, Corresponds with Reduced Bioavailability of Latent TGF\u03b2 in Mucolipidosis II Cells.\u00a0<\/a>Biomolecules.\u00a02020 Apr 26;10(5).\u00a0doi: 10.3390\/biom10050670.\u00a0PubMed PMID: 32357547; PubMed Central PMCID: PMC7277838.\r\n\r\nKlaver E, Zhao P, May M, Flanagan-Steet H<\/strong>, Freeze HH, Gilmore R, Wells L, Contessa J, Steet R.\u00a0Selective inhibition of N-linked glycosylation impairs receptor tyrosine kinase processing.\u00a0<\/a>Dis Model Mech.\u00a02019 Jun 5;12(6).\u00a0doi: 10.1242\/dmm.039602.\u00a0PubMed PMID: 31101650; PubMed Central PMCID: PMC6602306.\r\n\r\nFlanagan-Steet H<\/strong>, Christian C, Lu PN, Aarnio-Peterson M, Sanman L, Archer-Hartmann S, Azadi P, Bogyo M, Steet RA.\u00a0TGF-\u00df Regulates Cathepsin Activation during Normal and Pathogenic Development.\u00a0<\/a>Cell Rep.\u00a02018 Mar 13;22(11):2964-2977.\u00a0doi: 10.1016\/j.celrep.2018.02.066.\u00a0PubMed PMID: 29539424; PubMed Central PMCID: PMC6247414.\r\n\r\nAarnio-Peterson M, Zhao P, Yu SH, Christian C, Flanagan-Steet H<\/strong>, Wells L, Steet R.\u00a0Altered Met receptor phosphorylation and LRP1-mediated uptake in cells lacking carbohydrate-dependent lysosomal targeting.\u00a0<\/a>J Biol Chem.\u00a02017 Sep 8;292(36):15094-15104.\u00a0doi: 10.1074\/jbc.M117.790139.\u00a0Epub 2017 Jul 19.\u00a0PubMed PMID: 28724630; PubMed Central PMCID: PMC5592684.\r\n\r\nFlanagan-Steet H<\/strong>, Matheny C, Petrey A, Parker J, Steet R.\u00a0Enzyme-specific differences in mannose phosphorylation between GlcNAc-1-phosphotransferase \u03b1\u03b2 and \u03b3 subunit deficient zebrafish support cathepsin proteases as early mediators of mucolipidosis pathology.\u00a0<\/a>Biochim Biophys Acta.\u00a02016 Sep;1860(9):1845-53.\u00a0doi: 10.1016\/j.bbagen.2016.05.029.\u00a0Epub 2016 May 27.\u00a0PubMed PMID: 27241848; PubMed Central PMCID: PMC4949139.\r\n\r\nFlanagan-Steet H, Aarnio M, Kwan B, Guihard P, Petrey A, Haskins M, Blanchard F, Steet R<\/strong>.\u00a0Cathepsin-Mediated Alterations in TGF\u00df-Related Signaling Underlie Disrupted Cartilage and Bone Maturation Associated With Impaired Lysosomal Targeting.\u00a0<\/a>J Bone Miner Res.\u00a02016 Mar;31(3):535-48.\u00a0doi: 10.1002\/jbmr.2722.\u00a0Epub 2015 Oct 13.\u00a0PubMed PMID: 26404503; PubMed Central PMCID: PMC4808492.","_et_gb_content_width":"","footnotes":"","_links_to":"","_links_to_target":""},"categories":[12],"tags":[],"class_list":["post-972","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-faculty"],"_links":{"self":[{"href":"https:\/\/scienceweb.clemson.edu\/ihg\/wp-json\/wp\/v2\/posts\/972","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/scienceweb.clemson.edu\/ihg\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/scienceweb.clemson.edu\/ihg\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/scienceweb.clemson.edu\/ihg\/wp-json\/wp\/v2\/users\/13"}],"replies":[{"embeddable":true,"href":"https:\/\/scienceweb.clemson.edu\/ihg\/wp-json\/wp\/v2\/comments?post=972"}],"version-history":[{"count":0,"href":"https:\/\/scienceweb.clemson.edu\/ihg\/wp-json\/wp\/v2\/posts\/972\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/scienceweb.clemson.edu\/ihg\/wp-json\/wp\/v2\/media\/973"}],"wp:attachment":[{"href":"https:\/\/scienceweb.clemson.edu\/ihg\/wp-json\/wp\/v2\/media?parent=972"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/scienceweb.clemson.edu\/ihg\/wp-json\/wp\/v2\/categories?post=972"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/scienceweb.clemson.edu\/ihg\/wp-json\/wp\/v2\/tags?post=972"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}