ABOUT THE RESEARCHER

OVERVIEW

Visit the Human Pluripotent Stem Cell Technology Core facility.

Our research efforts focus on generation and directed differentiation of pluripotent stem cells. We combine fluorescent imaging and other stem cell based assays with chemical genetics and high-throughput screening approaches to identify genes, agents, and pathways that affect the formation, function, and fate of pluripotent stem cells. Our main long-term goal is to derive clinical-grade blood stem cells from patient-specific pluripotent stem cells.

BACKGROUND

Dr Schlaeger holds a PhD in Human Biology from Philipps University in Marburg, Germany (1998). He received the Otto Hahn medal for work on endothelial specific gene regulation, which he performed as a graduate student in the laboratories of the late Dr. Werner Risau (Max Planck Institute) and Dr. Tom N. Sato (Beth Israel Deaconess Hospital). Dr. Schlaeger then joined Dr. Stuart Orkin's laboratory at Children's Hospital Boston in 1999 where he studied the role of the stem cell leukemia gene in endothelial and hematopoetic stem cells. Following a 16-month stint as Senior Scientist running gene targeting projects in the mouse genetics group of Cell and Molecular Technologies Inc. (now part of Invitrogen), Dr. Schlaeger returned to Children's in 2005 to serve as Head of the Human Embryonic Stem Cell Core Facility within the hospital's Stem Cell Program.

PUBLICATIONS

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  1. Congenital X-linked neutropenia with myelodysplasia and somatic tetraploidy due to a germline mutation in SEPT6. Am J Hematol. 2022 Jan 01; 97(1):18-29. View abstract
  2. Genome sequencing unveils a regulatory landscape of platelet reactivity. Nat Commun. 2021 06 15; 12(1):3626. View abstract
  3. A recurrent, homozygous EMC10 frameshift variant is associated with a syndrome of developmental delay with variable seizures and dysmorphic features. Genet Med. 2021 06; 23(6):1158-1162. View abstract
  4. Derivation of Airway Basal Stem Cells from Human Pluripotent Stem Cells. Cell Stem Cell. 2021 01 07; 28(1):79-95.e8. View abstract
  5. An induced pluripotent stem cell model of Fanconi anemia reveals mechanisms of p53-driven progenitor cell differentiation. Blood Adv. 2020 10 13; 4(19):4679-4692. View abstract
  6. Mitochondrial and Redox Modifications in Huntington Disease Induced Pluripotent Stem Cells Rescued by CRISPR/Cas9 CAGs Targeting. Front Cell Dev Biol. 2020; 8:576592. View abstract
  7. Integrative Genomic Analysis Reveals Four Protein Biomarkers for Platelet Traits. Circ Res. 2020 10 09; 127(9):1182-1194. View abstract
  8. A Platelet Function Modulator of Thrombin Activation Is Causally Linked to Cardiovascular Disease and Affects PAR4 Receptor Signaling. Am J Hum Genet. 2020 08 06; 107(2):211-221. View abstract
  9. Transcriptome Dynamics of Hematopoietic Stem Cell Formation Revealed Using a Combinatorial Runx1 and Ly6a Reporter System. Stem Cell Reports. 2020 05 12; 14(5):956-971. View abstract
  10. Xeno-Free Reprogramming of Peripheral Blood Mononuclear Erythroblasts on Laminin-521. Curr Protoc Stem Cell Biol. 2020 03; 52(1):e103. View abstract
  11. Morphological and Molecular Defects in Human Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis. Stem Cell Reports. 2019 11 12; 13(5):906-923. View abstract
  12. Author Correction: Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow engraftment. Nature. 2019 Sep; 573(7772):E1. View abstract
  13. Applying Deep Neural Network Analysis to High-Content Image-Based Assays. SLAS Discov. 2019 09; 24(8):829-841. View abstract
  14. The Lin28/let-7 Pathway Regulates the Mammalian Caudal Body Axis Elongation Program. Dev Cell. 2019 02 11; 48(3):396-405.e3. View abstract
  15. H3K9 methyltransferases and demethylases control lung tumor-propagating cells and lung cancer progression. Nat Commun. 2018 11 19; 9(1):4559. View abstract
  16. The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles. Cell Rep. 2018 07 24; 24(4):973-986.e8. View abstract
  17. Nonintegrating Human Somatic Cell Reprogramming Methods. Adv Biochem Eng Biotechnol. 2018; 163:1-21. View abstract
  18. A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest development. Elife. 2017 08 23; 6. View abstract
  19. Using CRISPR-Cas9 to Generate Gene-Corrected Autologous iPSCs for the Treatment of Inherited Retinal Degeneration. Mol Ther. 2017 09 06; 25(9):1999-2013. View abstract
  20. Drug discovery for Diamond-Blackfan anemia using reprogrammed hematopoietic progenitors. Sci Transl Med. 2017 02 08; 9(376). View abstract
  21. Developmental Vitamin D Availability Impacts Hematopoietic Stem Cell Production. Cell Rep. 2016 10 04; 17(2):458-468. View abstract
  22. Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow engraftment. Nature. 2015 Jul 23; 523(7561):468-71. View abstract
  23. Reticular dysgenesis-associated AK2 protects hematopoietic stem and progenitor cell development from oxidative stress. J Exp Med. 2015 Jul 27; 212(8):1185-202. View abstract
  24. Flow-induced protein kinase A-CREB pathway acts via BMP signaling to promote HSC emergence. J Exp Med. 2015 May 04; 212(5):633-48. View abstract
  25. Adenosine signaling promotes hematopoietic stem and progenitor cell emergence. J Exp Med. 2015 May 04; 212(5):649-63. View abstract
  26. Notch1 acts via Foxc2 to promote definitive hematopoiesis via effects on hemogenic endothelium. Blood. 2015 Feb 26; 125(9):1418-26. View abstract
  27. A comparison of non-integrating reprogramming methods. Nat Biotechnol. 2015 Jan; 33(1):58-63. View abstract
  28. TMEM14C is required for erythroid mitochondrial heme metabolism. J Clin Invest. 2014 Oct; 124(10):4294-304. View abstract
  29. Neurotrophin receptor TrkB promotes lung adenocarcinoma metastasis. Proc Natl Acad Sci U S A. 2014 Jul 15; 111(28):10299-304. View abstract
  30. Differential role of nonhomologous end joining factors in the generation, DNA damage response, and myeloid differentiation of human induced pluripotent stem cells. Proc Natl Acad Sci U S A. 2014 Jun 17; 111(24):8889-94. View abstract
  31. Iron regulatory protein-1 protects against mitoferrin-1-deficient porphyria. J Biol Chem. 2014 May 16; 289(20):13707. View abstract
  32. Iron regulatory protein-1 protects against mitoferrin-1-deficient porphyria. J Biol Chem. 2014 Mar 14; 289(11):7835-43. View abstract
  33. iPSC-derived neurons as a higher-throughput readout for autism: promises and pitfalls. Trends Mol Med. 2014 Feb; 20(2):91-104. View abstract
  34. Pluripotent stem cell models of Shwachman-Diamond syndrome reveal a common mechanism for pancreatic and hematopoietic dysfunction. Cell Stem Cell. 2013 Jun 06; 12(6):727-36. View abstract
  35. Impaired intrinsic immunity to HSV-1 in human iPSC-derived TLR3-deficient CNS cells. Nature. 2012 Nov 29; 491(7426):769-73. View abstract
  36. Induced pluripotent stem cells as a tool for gaining new insights into Fanconi anemia. Cell Cycle. 2012 Aug 15; 11(16):2985-90. View abstract
  37. Overcoming reprogramming resistance of Fanconi anemia cells. Blood. 2012 Jun 07; 119(23):5449-57. View abstract
  38. The mitochondrial transporter ABC-me (ABCB10), a downstream target of GATA-1, is essential for erythropoiesis in vivo. Cell Death Differ. 2012 Jul; 19(7):1117-26. View abstract
  39. Live-cell immunofluorescence staining of human pluripotent stem cells. Curr Protoc Stem Cell Biol. 2011 Dec; Chapter 1:Unit 1C.12. View abstract
  40. Prostaglandin E2 enhances human cord blood stem cell xenotransplants and shows long-term safety in preclinical nonhuman primate transplant models. Cell Stem Cell. 2011 Apr 08; 8(4):445-58. View abstract
  41. A call for standardized naming and reporting of human ESC and iPSC lines. Cell Stem Cell. 2011 Apr 08; 8(4):357-9. View abstract
  42. Generation of induced pluripotent stem cell lines from human fibroblasts via retroviral gene transfer. Methods Mol Biol. 2011; 767:55-65. View abstract
  43. Induced pluripotent stem cells: a novel frontier in the study of human primary immunodeficiencies. J Allergy Clin Immunol. 2011 Jun; 127(6):1400-7.e4. View abstract
  44. Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nat Genet. 2010 Dec; 42(12):1113-7. View abstract
  45. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell. 2010 Nov 05; 7(5):618-30. View abstract
  46. Clump passaging and expansion of human embryonic and induced pluripotent stem cells on mouse embryonic fibroblast feeder cells. Curr Protoc Stem Cell Biol. 2010 Aug; Chapter 1:Unit 1C.10. View abstract
  47. Knockdown of Fanconi anemia genes in human embryonic stem cells reveals early developmental defects in the hematopoietic lineage. Blood. 2010 Apr 29; 115(17):3453-62. View abstract
  48. Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts. Nat Genet. 2009 Dec; 41(12):1350-3. View abstract
  49. Live cell imaging distinguishes bona fide human iPS cells from partially reprogrammed cells. Nat Biotechnol. 2009 Nov; 27(11):1033-7. View abstract
  50. Improved electrospray ionization efficiency compensates for diminished chromatographic resolution and enables proteomics analysis of tyrosine signaling in embryonic stem cells. Anal Chem. 2009 May 01; 81(9):3440-7. View abstract
  51. Enhanced plating efficiency of trypsin-adapted human embryonic stem cells is reversible and independent of trisomy 12/17. . 2008 Mar; 10(1):107-18. View abstract
  52. Inducible endothelial cell-specific gene expression in transgenic mouse embryos and adult mice. Exp Cell Res. 2008 Apr 01; 314(6):1202-16. View abstract
  53. Derivation and maintenance of human embryonic stem cells from poor-quality in vitro fertilization embryos. Nat Protoc. 2008; 3(5):923-33. View abstract
  54. Teratoma formation assays with human embryonic stem cells: a rationale for one type of human-animal chimera. Cell Stem Cell. 2007 Sep 13; 1(3):253-8. View abstract
  55. Science aside: the trajectory of embryonic stem cell research in the USA. Drug Discov Today. 2007 Apr; 12(7-8):269-71. View abstract
  56. Pluripotent stem cells and their niches. Stem Cell Rev. 2006; 2(3):185-201. View abstract
  57. Tie2Cre-mediated gene ablation defines the stem-cell leukemia gene (SCL/tal1)-dependent window during hematopoietic stem-cell development. Blood. 2005 May 15; 105(10):3871-4. View abstract
  58. Decoding hematopoietic specificity in the helix-loop-helix domain of the transcription factor SCL/Tal-1. Mol Cell Biol. 2004 Sep; 24(17):7491-502. View abstract
  59. Haematopoietic stem cells retain long-term repopulating activity and multipotency in the absence of stem-cell leukaemia SCL/tal-1 gene. Nature. 2003 Jan 30; 421(6922):547-51. View abstract
  60. Expression of CD41 marks the initiation of definitive hematopoiesis in the mouse embryo. Blood. 2003 Jan 15; 101(2):508-16. View abstract
  61. Endothelium-specific replacement of the connexin43 coding region by a lacZ reporter gene. Genesis. 2001 Jan; 29(1):1-13. View abstract
  62. Role of SCL/Tal-1, GATA, and ets transcription factor binding sites for the regulation of flk-1 expression during murine vascular development. Blood. 2000 Nov 01; 96(9):3078-85. View abstract
  63. Uniform vascular-endothelial-cell-specific gene expression in both embryonic and adult transgenic mice. Proc Natl Acad Sci U S A. 1997 Apr 01; 94(7):3058-63. View abstract
  64. Vascular endothelial cell lineage-specific promoter in transgenic mice. Development. 1995 Apr; 121(4):1089-98. View abstract