{"id":3010,"date":"2022-12-21T12:17:26","date_gmt":"2022-12-21T17:17:26","guid":{"rendered":"https:\/\/labs.icahn.mssm.edu\/design\/?page_id=3010"},"modified":"2023-11-03T10:35:54","modified_gmt":"2023-11-03T14:35:54","slug":"research","status":"publish","type":"page","link":"https:\/\/labs.icahn.mssm.edu\/papapetroulab\/research\/","title":{"rendered":"Research"},"content":{"rendered":"

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Clonal evolution of AML<\/h2>\n

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AML develops through the step-wise acquisition of driver mutations\u00a0by a hematopoietic stem or progenitor cell (HSPC), which clonally expands while gradually gaining malignant features. We have created unique iPSC-based models to study this clonal evolution process, using (1) reprogramming of patient cells into iPSCs, and (2) CRISPR\/Cas9-mediated precise gene editing to introduce or correct driver mutations in isogenic iPSCs. The leukemia cells derived from these iPSCs closely resemble primary patient cells and enable us to perform functional in vitro studies, as well as in vivo xenograft studies to discover new disease biology and new targets for therapeutic development. We have more recently developed temporally controlled and reversible mutant alleles to address two fundamental questions: (1) How does the order of mutational acquisition affect leukemogenesis? (2) Are fully transformed AML cells still dependent on preleukemic mutations?<\/p>\n

\u00a0<\/strong><\/p>\n

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Read More<\/strong><\/h2>\n

Patient-Derived iPSCs Faithfully Represent the Genetic Diversity and Cellular Architecture of Human Acute Myeloid Leukemia<\/a><\/strong><\/p>\n

Sequential CRISPR gene editing in human iPSCs charts the clonal evolution of myeloid leukemia and identifies early disease targets<\/span><\/a><\/strong><\/p>\n

Stage-Specific Human Induced Pluripotent Stem Cells Map the Progression of Myeloid Transformation to Transplantable Leukemia<\/span><\/a><\/strong><\/p>\n

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Splicing factor mutations in MDS<\/strong><\/h1>\n

Splicing factor (SF) mutations are the most common and disease-defining class of somatic mutations in MDS, but how they drive disease is not understood. We created isogenic human iPSC models of SF mutations with allele-specific epitope tags and performed integrative analyses of mRNA binding and altered splicing. We discovered that SRSF2 and U2AF1 mutations converge in promoting a long isoform of the gene GNAS<\/em>, which encodes a longer and more active form of the G protein subunit G\u03b1s and activates MAPK\/ERK signaling. We are currently pursuing various ways to therapeutically target GNAS\/G\u03b1s.<\/p>\n

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Read More<\/strong><\/h2>\n

Patient-specific MDS-RS iPSCs define the mis-spliced transcript repertoire and chromatin landscape of\u00a0SF3B1<\/em>-mutant HSPCs<\/a><\/strong><\/p>\n

Integrative RNA-omics Discovers\u00a0GNAS<\/em>\u00a0Alternative Splicing as a Phenotypic Driver of Splicing Factor\u2013Mutant Neoplasms<\/a><\/strong><\/p>\n

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Clonal hematopoiesis<\/strong><\/h1>\n

We have generated isogenic iPSC models of the 3 main CH mutations \u2013 TET2, DNMT3A and ASXL1 \u00ad\u2013 and are performing integrative multi-omics analyses to identify cell-autonomous effects that underlie the clonal advantage of HSPCs that carry them.<\/p>\n

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Contact Us<\/strong><\/span><\/p>\n

[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”1_3,1_3,1_3″ _builder_version=”4.9.0″ background_color=”#FFFFFF” background_color_gradient_direction=”38deg” module_alignment=”center” custom_margin=”|auto|-2px|auto||” custom_padding=”0px|||||” locked=”off” collapsed=”on”][et_pb_column type=”1_3″ _builder_version=”4.9.0″ custom_padding=”|||” custom_padding__hover=”|||”][et_pb_text _builder_version=”4.9.0″ _module_preset=”default” text_font=”||||||||” text_text_color=”#FFFFFF” text_line_height=”22px”]<\/p>\n

Resources<\/b><\/span><\/p>\n

Department of Oncological Sciences<\/span><\/a>
 Black Family Stem Cell Institute<\/span><\/a>
 Tisch Cancer Institute<\/span><\/a>
 Graduate School of Biomedical Sciences<\/span><\/a>
 American Society of Hematology<\/span><\/a>
 American Society of Gene and Cell Therapy<\/span><\/a>
 International Society for Stem Cell Research<\/span><\/a><\/p>\n

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Papapetrou Lab
<\/strong>Department of Oncological Sciences
Icahn School of Medicine at Mount Sinai
One Gustave L. Levy Place
Box 1044A
New York, NY 10029
Phone: 212-824-9337
E-mail:<\/span>\u00a0<\/strong>eirini.papapetrou@mssm.edu<\/a><\/span><\/span><\/p>\n

 <\/p>\n

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Courier
<\/strong><\/span>Hess Center for Science and Medicine
<\/span>1470 Madison Ave, 6th FL., Rm. 112
<\/span>New York, NY 10029
<\/span>Phone: \u00a0212-824-9337
<\/span>Lab: \u00a0S6-202<\/p>\n

Support Staff
<\/strong><\/span>Genevieve Joseph<\/span>
Administrative Assistant<\/span>
Phone: \u00a0212-824-9367<\/span>
 genevieve.joseph@mssm.edu<\/span><\/a><\/p>\n

<\/strong><\/span><\/p>\n

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Clonal evolution of AMLAML develops through the step-wise acquisition of driver mutations\u00a0by a hematopoietic stem or progenitor cell (HSPC), which clonally expands while gradually gaining malignant features. We have created unique iPSC-based models to study this clonal evolution process, using (1) reprogramming of patient cells into iPSCs, and (2) CRISPR\/Cas9-mediated precise gene editing to introduce […]<\/p>\n","protected":false},"author":545,"featured_media":0,"parent":0,"menu_order":3,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"","_et_gb_content_width":"","inline_featured_image":false,"footnotes":""},"class_list":["post-3010","page","type-page","status-publish","hentry"],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/labs.icahn.mssm.edu\/papapetroulab\/wp-json\/wp\/v2\/pages\/3010","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/labs.icahn.mssm.edu\/papapetroulab\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/labs.icahn.mssm.edu\/papapetroulab\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/labs.icahn.mssm.edu\/papapetroulab\/wp-json\/wp\/v2\/users\/545"}],"replies":[{"embeddable":true,"href":"https:\/\/labs.icahn.mssm.edu\/papapetroulab\/wp-json\/wp\/v2\/comments?post=3010"}],"version-history":[{"count":144,"href":"https:\/\/labs.icahn.mssm.edu\/papapetroulab\/wp-json\/wp\/v2\/pages\/3010\/revisions"}],"predecessor-version":[{"id":5233,"href":"https:\/\/labs.icahn.mssm.edu\/papapetroulab\/wp-json\/wp\/v2\/pages\/3010\/revisions\/5233"}],"wp:attachment":[{"href":"https:\/\/labs.icahn.mssm.edu\/papapetroulab\/wp-json\/wp\/v2\/media?parent=3010"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}