Research

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Thorsten  Schlaeger, PhD

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Research Center:
Dana-Farber/Boston Children’s Cancer and Blood Disorders Center
Program:
Stem Cell Program
Department:
Medicine Research
Division
Hematology/Oncology Research
Hospital Title:
Principal Investigator; Head of hESC Core Lab, Stem Cell Program
Academic Title:
Instructor in Pediatrics, Harvard Medical School
Research Focus Area:
Stem Cell Program
Contact:
617-919-2082
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Research Overview

Visit The hESC 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.

About Thorsten Schlaeger, PhD

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. Rissone A, Weinacht KG, la Marca G, Bishop K, Giocaliere E, Jagadeesh J, Felgentreff K, Dobbs K, Al-Herz W, Jones M, Chandrasekharappa S, Kirby M, Wincovitch S, Simon KL, Itan Y, DeVine A, Schlaeger T, Schambach A, Sood R, Notarangelo LD, Candotti F. Reticular dysgenesis-associated AK2 protects hematopoietic stem and progenitor cell development from oxidative stress. J Exp Med. 2015 Jul 27; 212(8):1185-202.
  2. Jing L, Tamplin OJ, Chen MJ, Deng Q, Patterson S, Kim PG, Durand EM, McNeil A, Green JM, Matsuura S, Ablain J, Brandt MK, Schlaeger TM, Huttenlocher A, Daley GQ, Ravid K, Zon LI. Adenosine signaling promotes hematopoietic stem and progenitor cell emergence. J Exp Med. 2015 May 4; 212(5):649-63.
  3. Schlaeger TM, Daheron L, Brickler TR, Entwisle S, Chan K, Cianci A, DeVine A, Ettenger A, Fitzgerald K, Godfrey M, Gupta D, McPherson J, Malwadkar P, Gupta M, Bell B, Doi A, Jung N, Li X, Lynes MS, Brookes E, Cherry AB, Demirbas D, Tsankov AM, Zon LI, Rubin LL, Feinberg AP, Meissner A, Cowan CA, Daley GQ. A comparison of non-integrating reprogramming methods. Nat Biotechnol. 2015 Jan; 33(1):58-63.
  4. Sinkevicius KW, Kriegel C, Bellaria KJ, Lee J, Lau AN, Leeman KT, Zhou P, Beede AM, Fillmore CM, Caswell D, Barrios J, Wong KK, Sholl LM, Schlaeger TM, Bronson RT, Chirieac LR, Winslow MM, Haigis MC, Kim CF. Neurotrophin receptor TrkB promotes lung adenocarcinoma metastasis. Proc Natl Acad Sci U S A. 2014 Jul 15; 111(28):10299-304.
  5. Chung J, Anderson SA, Gwynn B, Deck KM, Chen MJ, Langer NB, Shaw GC, Huston NC, Boyer LF, Datta S, Paradkar PN, Li L, Wei Z, Lambert AJ, Sahr K, Wittig JG, Chen W, Lu W, Galy B, Schlaeger TM, Hentze MW, Ward DM, Kaplan J, Eisenstein RS, Peters LL, Paw BH. Iron regulatory protein-1 protects against mitoferrin-1-deficient porphyria. J Biol Chem. 2014 May 16; 289(20):13707.
  6. Prilutsky D, Palmer NP, Smedemark-Margulies N, Schlaeger TM, Margulies DM, Kohane IS. iPSC-derived neurons as a higher-throughput readout for autism: promises and pitfalls. Trends Mol Med. 2014 Feb; 20(2):91-104.
  7. Lafaille FG, Pessach IM, Zhang SY, Ciancanelli MJ, Herman M, Abhyankar A, Ying SW, Keros S, Goldstein PA, Mostoslavsky G, Ordovas-Montanes J, Jouanguy E, Plancoulaine S, Tu E, Elkabetz Y, Al-Muhsen S, Tardieu M, Schlaeger TM, Daley GQ, Abel L, Casanova JL, Studer L, Notarangelo LD. Impaired intrinsic immunity to HSV-1 in human iPSC-derived TLR3-deficient CNS cells. Nature. 2012 Nov 29; 491(7426):769-73.
  8. Müller LU, Schlaeger TM, DeVine AL, Williams DA. Induced pluripotent stem cells as a tool for gaining new insights into Fanconi anemia. Cell Cycle. 2012 Aug 15; 11(16):2985-90.
  9. Müller LU, Milsom MD, Harris CE, Vyas R, Brumme KM, Parmar K, Moreau LA, Schambach A, Park IH, London WB, Strait K, Schlaeger T, Devine AL, Grassman E, D'Andrea A, Daley GQ, Williams DA. Overcoming reprogramming resistance of Fanconi anemia cells. Blood. 2012 Jun 7; 119(23):5449-57.
  10. Manos PD, Ratanasirintrawoot S, Loewer S, Daley GQ, Schlaeger TM. Live-cell immunofluorescence staining of human pluripotent stem cells. Curr Protoc Stem Cell Biol. 2011 Dec; Chapter 1:Unit 1C.12.
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  12. Goessling W, Allen RS, Guan X, Jin P, Uchida N, Dovey M, Harris JM, Metzger ME, Bonifacino AC, Stroncek D, Stegner J, Armant M, Schlaeger T, Tisdale JF, Zon LI, Donahue RE, North TE. 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 8; 8(4):445-58.
  13. Miller JD, Schlaeger TM. Generation of induced pluripotent stem cell lines from human fibroblasts via retroviral gene transfer. Methods Mol Biol. 2011; 767:55-65.
  14. Hartung O, Huo H, Daley GQ, Schlaeger TM. 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.
  15. Tulpule A, Lensch MW, Miller JD, Austin K, D'Andrea A, Schlaeger TM, Shimamura A, Daley GQ. 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.
  16. Chan EM, Ratanasirintrawoot S, Park IH, Manos PD, Loh YH, Huo H, Miller JD, Hartung O, Rho J, Ince TA, Daley GQ, Schlaeger TM. Live cell imaging distinguishes bona fide human iPS cells from partially reprogrammed cells. Nat Biotechnol. 2009 Nov; 27(11):1033-7.
  17. Ficarro SB, Zhang Y, Lu Y, Moghimi AR, Askenazi M, Hyatt E, Smith ED, Boyer L, Schlaeger TM, Luckey CJ, Marto JA. Improved electrospray ionization efficiency compensates for diminished chromatographic resolution and enables proteomics analysis of tyrosine signaling in embryonic stem cells. Anal Chem. 2009 May 1; 81(9):3440-7.
  18. Chan EM, Yates F, Boyer LF, Schlaeger TM, Daley GQ. Enhanced plating efficiency of trypsin-adapted human embryonic stem cells is reversible and independent of trisomy 12/17. Cloning Stem Cells. 2008 Mar; 10(1):107-18.
  19. Deutsch U, Schlaeger TM, Dehouck B, Döring A, Tauber S, Risau W, Engelhardt B. Inducible endothelial cell-specific gene expression in transgenic mouse embryos and adult mice. Exp Cell Res. 2008 Apr 1; 314(6):1202-16.
  20. Lerou PH, Yabuuchi A, Huo H, Miller JD, Boyer LF, Schlaeger TM, Daley GQ. Derivation and maintenance of human embryonic stem cells from poor-quality in vitro fertilization embryos. Nat Protoc. 2008; 3(5):923-33.
  21. Lensch MW, Schlaeger TM, Zon LI, Daley GQ. 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.
  22. Schlaeger TM, Lensch MW, Taylor PL. Science aside: the trajectory of embryonic stem cell research in the USA. Drug Discov Today. 2007 Apr; 12(7-8):269-71.
  23. Lensch MW, Daheron L, Schlaeger TM. Pluripotent stem cells and their niches. Stem Cell Rev. 2006; 2(3):185-201.
  24. Schlaeger TM, Mikkola HK, Gekas C, Helgadottir HB, Orkin SH. 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.
  25. Schlaeger TM, Schuh A, Flitter S, Fisher A, Mikkola H, Orkin SH, Vyas P, Porcher C. 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.
  26. Mikkola HK, Klintman J, Yang H, Hock H, Schlaeger TM, Fujiwara Y, Orkin SH. 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.
  27. Mikkola HK, Fujiwara Y, Schlaeger TM, Traver D, Orkin SH. Expression of CD41 marks the initiation of definitive hematopoiesis in the mouse embryo. Blood. 2003 Jan 15; 101(2):508-16.
  28. Theis M, de Wit C, Schlaeger TM, Eckardt D, Krüger O, Döring B, Risau W, Deutsch U, Pohl U, Willecke K. Endothelium-specific replacement of the connexin43 coding region by a lacZ reporter gene. Genesis. 2001 Jan; 29(1):1-13.
  29. Kappel A, Schlaeger TM, Flamme I, Orkin SH, Risau W, Breier G. 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 1; 96(9):3078-85.
  30. Schlaeger TM, Bartunkova S, Lawitts JA, Teichmann G, Risau W, Deutsch U, Sato TN. Uniform vascular-endothelial-cell-specific gene expression in both embryonic and adult transgenic mice. Proc Natl Acad Sci U S A. 1997 Apr 1; 94(7):3058-63.
  31. Schlaeger TM, Qin Y, Fujiwara Y, Magram J, Sato TN. Vascular endothelial cell lineage-specific promoter in transgenic mice. Development. 1995 Apr; 121(4):1089-98.
  32. Warren L, Manos PD, Ahfeldt T, Loh YH, Li H, Lau F, Ebina W, Mandal PK, Smith ZD, Meissner A, Daley GQ, Brack AS, Collins JJ, Cowan C, Schlaeger TM, Rossi DJ. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell. 2010 Nov 5; 7(5):618-30.
  33. Luong MX, Auerbach J, Crook JM, Daheron L, Hei D, Lomax G, Loring JF, Ludwig T, Schlaeger TM, Smith KP, Stacey G, Xu RH, Zeng F. A call for standardized naming and reporting of human ESC and iPSC lines. Cell Stem Cell. 2011 Apr 8; 8(4):357-9.
  34. Pessach IM, Ordovas-Montanes J, Zhang SY, Casanova JL, Giliani S, Gennery AR, Al-Herz W, Manos PD, Schlaeger TM, Park IH, Rucci F, Agarwal S, Mostoslavsky G, Daley GQ, Notarangelo LD. 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.
  35. Doi A, Park IH, Wen B, Murakami P, Aryee MJ, Irizarry R, Herb B, Ladd-Acosta C, Rho J, Loewer S, Miller J, Schlaeger T, Daley GQ, Feinberg AP. 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.
  36. Loewer S, Cabili MN, Guttman M, Loh YH, Thomas K, Park IH, Garber M, Curran M, Onder T, Agarwal S, Manos PD, Datta S, Lander ES, Schlaeger TM, Daley GQ, Rinn JL. Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nat Genet. 2010 Dec; 42(12):1113-7.
  37. Hyde BB, Liesa M, Elorza AA, Qiu W, Haigh SE, Richey L, Mikkola HK, Schlaeger TM, Shirihai OS. 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.
  38. Tulpule A, Kelley JM, Lensch MW, McPherson J, Park IH, Hartung O, Nakamura T, Schlaeger TM, Shimamura A, Daley GQ. Pluripotent stem cell models of Shwachman-Diamond syndrome reveal a common mechanism for pancreatic and hematopoietic dysfunction. Cell Stem Cell. 2013 Jun 6; 12(6):727-36.
  39. Chung J, Anderson SA, Gwynn B, Deck KM, Chen MJ, Langer NB, Shaw GC, Huston NC, Boyer LF, Datta S, Paradkar PN, Li L, Wei Z, Lambert AJ, Sahr K, Wittig JG, Chen W, Lu W, Galy B, Schlaeger TM, Hentze MW, Ward DM, Kaplan J, Eisenstein RS, Peters LL, Paw BH. Iron regulatory protein-1 protects against mitoferrin-1-deficient porphyria. J Biol Chem. 2014 Mar 14; 289(11):7835-43.
  40. Felgentreff K, Du L, Weinacht KG, Dobbs K, Bartish M, Giliani S, Schlaeger T, DeVine A, Schambach A, Woodbine LJ, Davies G, Baxi SN, van der Burg M, Bleesing J, Gennery A, Manis J, Pan-Hammarström Q, Notarangelo LD. 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.
  41. Yien YY, Robledo RF, Schultz IJ, Takahashi-Makise N, Gwynn B, Bauer DE, Dass A, Yi G, Li L, Hildick-Smith GJ, Cooney JD, Pierce EL, Mohler K, Dailey TA, Miyata N, Kingsley PD, Garone C, Hattangadi SM, Huang H, Chen W, Keenan EM, Shah DI, Schlaeger TM, DiMauro S, Orkin SH, Cantor AB, Palis J, Koehler CM, Lodish HF, Kaplan J, Ward DM, Dailey HA, Phillips JD, Peters LL, Paw BH. TMEM14C is required for erythroid mitochondrial heme metabolism. J Clin Invest. 2014 Oct; 124(10):4294-304.
  42. Jang IH, Lu YF, Zhao L, Wenzel PL, Kume T, Datta SM, Arora N, Guiu J, Lagha M, Kim PG, Do EK, Kim JH, Schlaeger TM, Zon LI, Bigas A, Burns CE, Daley GQ. Notch1 acts via Foxc2 to promote definitive hematopoiesis via effects on hemogenic endothelium. Blood. 2015 Feb 26; 125(9):1418-26.
  43. Kim PG, Nakano H, Das PP, Chen MJ, Rowe RG, Chou SS, Ross SJ, Sakamoto KM, Zon LI, Schlaeger TM, Orkin SH, Nakano A, Daley GQ. Flow-induced protein kinase A-CREB pathway acts via BMP signaling to promote HSC emergence. J Exp Med. 2015 May 4; 212(5):633-48.
  44. Li P, Lahvic JL, Binder V, Pugach EK, Riley EB, Tamplin OJ, Panigrahy D, Bowman TV, Barrett FG, Heffner GC, McKinney-Freeman S, Schlaeger TM, Daley GQ, Zeldin DC, Zon LI. Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow engraftment. Nature. 2015 Jul 23; 523(7561):468-71.
  45. Cortes M, Chen MJ, Stachura DL, Liu SY, Kwan W, Wright F, Vo LT, Theodore LN, Esain V, Frost IM, Schlaeger TM, Goessling W, Daley GQ, North TE. Developmental Vitamin D Availability Impacts Hematopoietic Stem Cell Production. Cell Rep. 2016 Oct 4; 17(2):458-468.
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