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Main Profile

Full Name and Degrees: 
George Q. Daley, M.D., Ph.D.
Member Role: 
Lead Principal Investigator
Institutional affiliation: 
Children's Hospital Boston

My laboratory investigates hematopoiesis, pluripotency, and cancer, with an emphasis on common mechanisms in tissue development, epigenetic reprogramming, and oncogenesis. We have expertise in transgenic and knock-out mouse models of disease, hematopoietic transplantation in radiation chimeras, analysis of malignancy in xenograft models, reprogramming, and differentiation of pluripotent stem cells. I have 20+ years of experience directing collaborative scientific projects, and in mentoring scientists for transitions to positions in academia and industry.

research focus: 

The Daley lab exploits murine models and human cell culture systems to study human disease, with an emphasis on Hematopoietic Stem Cells (HSCs) in normal development and leukemia. We have directed the differentiation of murine Embryonic Stem (ES) cells into HSCs with the potential to engraft in irradiated mice (Kyba et al., Cell 2002; Wang et al., PNAS 2005; McKinney-Freeman et al., Blood 2009), and defined the transcriptional landscape of blood formation through isolation and characterization of embryonic HSCs (McKinney-Freeman et al, Cell Stem Cell 2012). Using selected transcription factors, we have re-specified lineage-restricted myeloid cells into multipotential myelo-erythroid progenitors, a first step towards direct conversion towards HSCs (Doulatov et al, Cell Stem Cell 2013). We discovered that shear forces from the embryonic heartbeat promote the emergence of HSCs during embryonic development, a phenomenon we have exploited to enhance blood formation from ES cells in vitro (Adamo et al., Nature 2009). We have modeled therapeutic transplantation in mice with “autologous” ES cells generated using nuclear transfer (Rideout et al., Cell 2002) and parthenogenesis (Kim et al., Science 2007). These studies establish murine models for combining gene and cell therapy for the treatment of genetic disease. In efforts to enhance hematopoietic recovery post-transplant, we have discovered that bone marrow adipocytes antagonize engraftment, and that drugs that block adipogenesis can accelerate marrow recovery (Naveiras et al., Nature 2009). Towards our goal of translating these studies to human blood disease modeling, we have directly reprogrammed human somatic cells with defined genes into induced pluripotent stem cells (iPS; Park et al, Nature 2008), created the first large repository of disease-specific iPS cell lines (Park et al., Cell 2008), described “epigenetic memory” in iPS cells as a technical limitation of reprogramming (Kim et al., Nature 2010), documented the role of chromatin modifying enzymes as modulators of reprogramming (Onder et al., Nature 2012), and defined the role of threonine catabolism in maintenance of pluripotency (Shyh-Chang et al, Science 2013). We are studying human disease-specific iPSC to illuminate aspects of bone marrow failure and other hematologic conditions (Agarwal et al., Nature 2010). Our most recent work has employed sets of transcription factors to convert pluripotent stem cell-derived hemogenic endothelium into hematopoietic stem and progenitor cells (Sugimura et al, Nature in press), bringing us tantalizingly close to realizing the production of bona fide HSCs in vitro. Our work supported by the PCTC entails using iPS-derived human blood disease models to discover small molecule therapeutics, including demonstrating the role of the autophagy activator SMER28 in ameliorating Diamond-Blackfan Anemia (Doulatov et al, Science Translational Medicine 2017).

Recent publications: 
Autophagy: It's in Your Blood. Doulatov S, Daley GQ. Dev Cell. 2017 Mar 27;40(6):518-520. doi: 10.1016/j.devcel.2017.03.011. Polar Extremes in the Clinical Use of Stem Cells. - Daley GQ. N Engl J Med. 2017 Mar 16;376(11):1075-1077. doi: 10.1056/NEJMe1701379. No abstract available. Drug discovery for Diamond-Blackfan anemia using reprogrammed hematopoietic progenitors. Doulatov S, Vo LT, Macari ER, Wahlster L, Kinney MA, Taylor AM, Barragan J, Gupta M, McGrath K, Lee HY, Humphries JM, DeVine A, Narla A, Alter BP, Beggs AH, Agarwal S, Ebert BL, Gazda HT, Lodish HF, Sieff CA, Schlaeger TM, Zon LI, Daley GQ.Sci Transl Med. 2017 Feb 8;9(376). pii: eaah5645. doi: 10.1126/scitranslmed.aah5645. Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma. Powers JT, Tsanov KM, Pearson DS, Roels F, Spina CS, Ebright R, Seligson M, de Soysa Y, Cahan P, Theißen J, Tu HC, Han A, Kurek KC, LaPier GS, Osborne JK, Ross SJ, Cesana M, Collins JJ, Berthold F, Daley GQ. New ISSCR guidelines: clinical translation of stem cell research. Kimmelman J, Heslop HE, Sugarman J, Studer L, Benvenisty N, Caulfield T, Hyun I, Murry CE, Sipp D, Daley GQ.
Division of Hematology/Oncology 1 Blackfan Circle, Room 7214 300 Longwood Avenue
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