CURRENT CLINICAL INTERESTS
myelodysplasia, gene therapy, regenerative medicine
CURRENT RESEARCH INTERESTS
modification and hematopoietic differentiation of human induced
pluripotent stem (iPS) cells, hematopoiesis, erythropoiesis,
myelodysplasia, gene therapy
Our laboratory aims to
understand normal and abnormal hematopoiesis with the goals of
identifying new therapeutic targets and developing novel cell and gene
Our major focus is the
investigation of the mechanisms and genetic basis of myelodysplasia.
Harnessing human induced pluripotent stem (iPS) cell technology, we
are developing new models of dysplastic hematopoiesis through the
reprogramming of patient-derived hematopoietic cells and the genetic
engineering of normal (wild-type) human pluripotent stem cells. Our
goal is to use genetic and chemical screens to identify candidate
genes and pathways responsible for the disease phenotype(s) and
further study their role in hematopoiesis.
In a second area of
research we are developing innovative technologies towards the use of
iPS cells in cell transplantation therapies. We have developed a
number of tools to generate transgene-free human iPS cells and to
genetically engineer them in safe harbor sites in the human genome.
Current projects include development of conditional suicide genes for
protection against teratoma formation, as well as identification of
universal genomic safe harbor sites for the genetic engineering of
F, Morrison GM, Sharov AA, Livigni A, Narayan S, O’Malley
J, Papapetrou EP,
Kaji K, Ko MSH,
Ptashne M, Brickman JM. Transcriptional activation by Oct4
is sufficient for the maintenance and induction of pluripotency. Cell
M, Papapetrou EP, Bushman
FD. Safe harbors for integration of new DNA in the human genome. Nature Reviews Cancer 2011 (Epub
ahead of print, PMID: 22129804).
Sadelain M. Generation of transgene-free human induced pluripotent
stem cells with an excisable single polycistronic vector. Nature
Sadelain M. Derivation of genetically modified human pluripotent stem
cells with integrated transgenes at unique mapped genomic sites. Nature
Protocols 2011; 6: 1274-1289.
Lee G, Malani N, Setty M, Riviere I, Tirunagari LMS, Kadota K, Roth,
SL, Giardina P, Viale A, Leslie C, Bushman FD, Studer L, Sadelain M.
Genomic safe harbors permit high b-globin
transgene expression in thalassemia induced pluripotent stem cells. Nature
Biotechnology 2011; 29(1): 73-8.
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; 8(6): 695-706.
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; 39(11): e72.
Müller F-Z, Schuldt B, Williams R, Mason D, Altun G, Papapetrou
EP, Danner S, Goldman JE, Herbst A, Schmidt NO, Aldenhoff JB,
Loring JF. A bioinformatic assay for pluripotency in human cells. Nature
2011; 8(4): 315-7.
Sadelain M. Reconstructing blood from induced pluripotent stem cells. F1000
Medicine Reports 2010, 2: 44.
JS, Maurin T, Robine N, Rasmussen K, Jeffrey K, Chandwani R, Papapetrou
EP, Sadelain M, O’Carroll D, Lai E. Conserved vertebrate miR-451
provides a platform for Dicer-independent, Ago2-mediated microRNA
biogenesis. Proc Natl Acad
Sci USA 2010;
Korkola JE, Sadelain M. A genetic strategy for single and
combinatorial analysis of miRNA function in mammalian hematopoietic
stem cells. Stem
Cells 2010; 28(2): 287-96.
G, Papapetrou EP, Kim H,
Chambers S, Tomishima M, Fasano C, Viale A, Tabar, V, Sadelain M,
Studer L. Modeling pathogenesis and treatment of familial dysautonomia
using patient-specific iPSCs. Nature
2009; 461(7262): 402-6.
Tomishima MJ, Chambers CM, Gruber 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.
Natl Acad Sci USA
2009; 106(31): 12759-64.
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
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. J Clin Invest 2009;
Ziros PG, Micheva ID, Zoumbos NC, Athanassiadou A. Gene transfer into
human hematopoietic progenitor cells with an episomal vector carrying
an S/MAR element. Gene
Therapy 2006; 13(1): 40-51.