Eirini Papapetrou, MD, PhD
- ASSOCIATE PROFESSOR | Oncological Sciences
- ASSOCIATE PROFESSOR | Medicine, Hematology and Medical Oncology
Research Topics:Cancer Genetics, Hematopoiesis, Stem Cells
Eirini Papapetrou studies blood disorders, particularly myeloid malignancies, with human pluripotent stem cells. Her lab developed the first iPSC models of Myelodysplastic Syndromes and Acute Myeloid Leukemia. The Papapetrou lab combines expertise in induced pluripotent stem (iPS) cell generation, genome editing (CRISPR) and hematopoiesis.
Multi-Disciplinary Training AreasCancer Biology [CAB], Clinical Research Education Program [CLR], Developmental and Stem Cell Biology [DSCB], Genetics and Genomic Sciences [GGS]
MD, University of Patras, Greece
PhD, University of Patras, Greece
Postdoctoral, Memorial Sloan-Kettering Cancer Center
Tito Bastianello Young Investigator Award
American Society for Clinical Investigation Young Physician-Scientist Award
Sidney Kimmel Foundation Scholar Award
UW Royalty Research Fund Award
American Society of Hematology (ASH) Junior Faculty Scholar Award
Aplastic Anemia & MDS IF Research Grant Award
John H. Tietze Stem Cell Scientist Award
Ellison Medical Foundation New Scholar in Aging Award
Damon Runyon-Rachleff Innovation Award
K99/R00 Pathway to Independence Award
Cellular alchemy meets genome engineering
We use human pluripotent stem cells to understand the mechanisms of malignant and non-malignant blood diseases and to develop new therapies. We are harnessing somatic cell reprogramming and genetic engineering technologies to develop new models of normal and abnormal hematopoiesis. By capturing and introducing disease-associated genetic mutations and large chromosomal deletions in patient-derived induced pluripotent stem cells (iPSCs) we study their phenotypic and functional consequences, attempt to reconstruct the genetic history of leukemia progression and seek to identify new therapeutic targets through genetic screens.
Genotype-driven modeling of Myelodysplastic Syndromes
Myelodysplastic syndromes (MDS) are clonal hematologic disorders characterized by ineffective hematopoiesis - manifested as peripheral blood cytopenia and dysplastic bone marrow (BM) - and a propensity for progression to BM failure or acute myeloid leukemia (AML) with poor prognosis. Although relatively common diseases, their pathogenesis is poorly understood.
We have recently established iPSC models of MDS that offer exciting new possibilities for the study of the molecular pathogenesis of MDS and the investigation of its genetics, clonal evolution and progression to leukemia and can provide a powerful platform for phenotype-based genetic and chemical screens to identify new therapeutic targets. We have also developed new strategies, combining AAV-mediated gene targeting with modified Cre-lox technology, as well as with the Cas9-CRISPR system, to engineer targeted chromosomal deletions in human iPSCs. These offer new opportunities to interrogate the functional consequences of large copy number variants associated with human cancer.
Kotini AG, Chang C, Boussaad I, Delrow JJ, Dolezal EK, Nagulapally AB, Perna F, Fishbein GA, Klimek VM, Hawkins RD, Huangfu D, Murry CE, Graubert T, Nimer SD, Papapetrou EP. Functional analysis of a chromosomal deletion associated with myelodysplastic syndromes using isogenic human induced pluripotent stem cells. Nature Biotechnology 2015 April;.
Perna F, Vu LP, Themeli M, Kriks S, Hoya-Arias R, Khanin R, Hricik T, Mansilla-Soto J, Papapetrou EP, Levine RL, Studer L, Sadelain M, Nimer SD. The Polycomb group protein L3MBTL1 represses a SMAD5-mediated hematopoietic transcriptional program in human pluripotent stem cells. Stem Cell Reports 2015 Mar;.
Oricchio E, Papapetrou EP, Lafaille F, Ganat YM, Kriks S, Ortega-Molina A, Mark WH, Teruya-Feldstein J, Huse JT, Reuter V, Sadelain M, Studer L, Wendel HG. A cell engineering strategy to enhance the safety of stem cell therapies. Cell Reports 2014 Sep; 8(6): 1677-85.
Davilla ML, Papapetrou EP. CARs move to the fast lane. Molecular Therapy 2014; 22(3).
Hammachi F, Morrison GM, Sharov AA, Livigni A, Narayan S, Papapetrou EP, O'Malley J, Kaji K, Ko MS, Ptashne M, Brickman JM. Transcriptional activation by Oct4 is sufficient for the maintenance and induction of pluripotency. Cell reports 2012 Feb; 1(2).
Papapetrou EP. FA iPS: correction or reprogramming first?. Blood 2012 Jun; 119(23).
Sadelain M, Papapetrou EP, Bushman FD. Safe harbours for the integration of new DNA in the human genome. Nature reviews. Cancer 2012 Jan; 12(1).
Papapetrou EP, Lee G, Malani N, Setty M, Riviere I, Tirunagari LM, Kadota K, Roth SL, Giardina P, Viale A, Leslie C, Bushman FD, Studer L, Sadelain M. Genomic safe harbors permit high β-globin transgene expression in thalassemia induced pluripotent stem cells. Nature biotechnology 2011 Jan; 29(1).
Papapetrou EP, Sadelain M. Derivation of genetically modified human pluripotent stem cells with integrated transgenes at unique mapped genomic sites. Nature protocols 2011 Sep; 6(9).
Papapetrou EP, Sadelain M. Generation of transgene-free human induced pluripotent stem cells with an excisable single polycistronic vector. Nature protocols 2011 Sep; 6(9).
Kim H, Lee G, Ganat Y, Papapetrou EP, Lipchina I, Socci ND, Sadelain M, Studer L. miR-371-3 expression predicts neural differentiation propensity in human pluripotent stem cells. Cell stem cell 2011 Jun; 8(6).
Brady T, Roth SL, Malani N, Wang GP, Berry CC, Leboulch P, Hacein-Bey-Abina S, Cavazzana-Calvo M, Papapetrou EP, Sadelain M, Savilahti H, Bushman FD. A method to sequence and quantify DNA integration for monitoring outcome in gene therapy. Nucleic acids research 2011 Jun; 39(11).
Müller FJ, Schuldt BM, Williams R, Mason D, Altun G, Papapetrou EP, Danner S, Goldmann JE, Herbst A, Schmidt NO, Aldenhoff JB, Laurent LC, Loring JF. A bioinformatic assay for pluripotency in human cells. Nature methods 2011 Apr; 8(4).
Papapetrou EP, Sadelain M. Reconstructing blood from induced pluripotent stem cells. F1000 medicine reports 2010; 2.
Yang JS, Maurin T, Robine N, Rasmussen KD, Jeffrey KL, Chandwani R, Papapetrou EP, Sadelain M, O'Carroll D, Lai EC. Conserved vertebrate mir-451 provides a platform for Dicer-independent, Ago2-mediated microRNA biogenesis. Proceedings of the National Academy of Sciences of the United States of America 2010 Aug; 107(34).
Papapetrou EP, Korkola JE, Sadelain M. A genetic strategy for single and combinatorial analysis of miRNA function in mammalian hematopoietic stem cells. Stem cells 2010 Feb; 28(2).
Lee G, Papapetrou EP, Kim H, Chambers SM, Tomishima MJ, Fasano CA, Ganat YM, Menon J, Shimizu F, Viale A, Tabar V, Sadelain M, Studer L. Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature 2009 Sep; 461(7262).
Papapetrou EP, Tomishima MJ, Chambers SM, Mica Y, Reed E, Menon J, Tabar V, Mo Q, Studer L, Sadelain M. Stoichiometric and temporal requirements of Oct4, Sox2, Klf4, and c-Myc expression for efficient human iPSC induction and differentiation. Proceedings of the National Academy of Sciences of the United States of America 2009 Aug; 106(31).
Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nature biotechnology 2009 Mar; 27(3).
Papapetrou EP, Kovalovsky D, Beloeil L, Sant'angelo D, Sadelain M. Harnessing endogenous miR-181a to segregate transgenic antigen receptor expression in developing versus post-thymic T cells in murine hematopoietic chimeras. The Journal of clinical investigation 2009 Jan; 119(1).