Photo of David T. Scadden,  MD

David T. Scadden, MD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 726-5615
Fax: (617) 724-2662


dscadden@mgh.harvard.edu

David T. Scadden, MD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Gerald and Darlene Jordan Professor of Medicine, Medicine, Harvard Medical School
  • Professor, Stem Cell and Regenerative Biology, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

The focus of the laboratory is hematopoietic stem cell biology emphasizing 1) cell cycle regulation, 2) lineage fate decisions, and 3) manipulation for stem cell-based therapies. The disease context in which these issues are being addressed is AIDS.

Publications

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  • Yu VW, Saez B, Cook C, Lotinun S, Pardo-Saganta A, Wang YH, Lymperi S, Ferraro F, Raaijmakers MH, Wu JY, Zhou L, Rajagopal J, Kronenberg HM, Baron R, Scadden DT. Specific bone cells produce DLL4 to generate thymus-seeding progenitors from bone marrow. J Exp Med 2015; 212:759-74. PubMed
  • Wang W, Yu S, Zimmerman G, Wang Y, Myers J, Yu VW, Huang D, Huang X, Shim J, Huang Y, Xin W, Qiao P, Yan M, Xin W, Scadden DT, Stanley P, Lowe JB, Huang AY, Siebel CW, Zhou L. Notch Receptor-Ligand Engagement Maintains Hematopoietic Stem Cell Quiescence and Niche Retention. Stem Cells 2015. PubMed
  • Kfoury Y, Scadden DT. Mesenchymal Cell Contributions to the Stem Cell Niche. Cell Stem Cell 2015; 16:239-253. PubMed
  • Chattopadhyay S, Stewart AL, Mukherjee S, Huang C, Hartwell KA, Miller PG, Subramanian R, Carmody LC, Yusuf RZ, Sykes DB, Paulk J, Vetere A, Vallet S, Santo L, Cirstea DD, Hideshima T, Dančík V, Majireck MM, Hussain MM, Singh S, Quiroz R, Iaconelli J, Karmacharya R, Tolliday NJ, Clemons PA, Moore MA, Stern AM, Shamji AF, Ebert BL, Golub TR, Raje NS, Scadden DT, Schreiber SL. Niche-Based Screening in Multiple Myeloma Identifies a Kinesin-5 Inhibitor with Improved Selectivity over Hematopoietic Progenitors. Cell Rep 2015. PubMed
  • Courties G, Herisson F, Sager HB, Heidt T, Ye Y, Wei Y, Sun Y, Severe N, Dutta P, Scharff J, Scadden DT, Weissleder R, Swirski FK, Moskowitz MA, Nahrendorf M. Ischemic stroke activates hematopoietic bone marrow stem cells. Circ Res 2015; 116:407-17. PubMed
  • Méndez-Ferrer S, Scadden DT, Sánchez-Aguilera A. Bone marrow stem cells: current and emerging concepts. Ann N Y Acad Sci 2015; 1335:32-44. PubMed
  • Lee D, Sykes SM, Kalaitzidis D, Lane AA, Kfoury Y, Raaijmakers MH, Wang YH, Armstrong SA, Scadden DT. Transmembrane Inhibitor of RICTOR/mTORC2 in Hematopoietic Progenitors. Stem Cell Reports 2014; 3:832-40. PubMed
  • Kfoury Y, Scadden DT. Cellular thrust and parry in the leukemic niche. Blood 2014; 124:2760-1. PubMed
  • Velardi E, Tsai JJ, Holland AM, Wertheimer T, Yu VW, Zakrzewski JL, Tuckett AZ, Singer NV, West ML, Smith OM, Young LF, Kreines FM, Levy ER, Boyd RL, Scadden DT, Dudakov JA, van den Brink MR. Sex steroid blockade enhances thymopoiesis by modulating Notch signaling. J Exp Med 2014. PubMed
  • Kalaitzidis D, Scadden DT. Deep diving in the blood stem cell-ome. EMBO J 2014; 33:2281-2. PubMed
  • Baryawno N, Scadden DT. Blood loses it when nerves go bad. Cell Res 2014; 24:1151-2. PubMed
  • Wang YH, Israelsen WJ, Lee D, Yu VW, Jeanson NT, Clish CB, Cantley LC, Vander Heiden MG, Scadden DT. Cell-state-specific metabolic dependency in hematopoiesis and leukemogenesis. Cell 2014; 158:1309-23. PubMed
  • Saez B, Ferraro F, Yusuf RZ, Cook CM, Yu VW, Pardo-Saganta A, Sykes SM, Palchaudhuri R, Schajnovitz A, Lotinun S, Lymperi S, Mendez-Ferrer S, Del Toro R, Day R, Vasic R, Acharya SS, Baron R, Lin CP, Yamaguchi Y, Wagers AJ, Scadden DT. Inhibiting stromal cell heparan sulfate synthesis improves stem cell mobilization and enables engraftment without cytotoxic conditioning. Blood 2014. PubMed
  • Choi YJ, Saez B, Anders L, Hydbring P, Stefano J, Bacon NA, Cook C, Kalaszczynska I, Signoretti S, Young RA, Scadden DT, Sicinski P. D-cyclins repress apoptosis in hematopoietic cells by controlling death receptor Fas and its ligand FasL. Dev Cell 2014; 30:255-67. PubMed
  • Kfoury Y, Mercier F, Scadden DT. SnapShot: The Hematopoietic Stem Cell Niche. Cell 2014; 158:228-228.e1. PubMed
  • Cho J, Yusuf R, Kook S, Attar E, Lee D, Park B, Cheng T, Scadden DT, Lee BC. Purinergic P2Y14 receptor modulates stress-induced hematopoietic stem/progenitor cell senescence. J Clin Invest 2014; 124:3159-71. PubMed
  • Kharchenko PV, Silberstein L, Scadden DT. Bayesian approach to single-cell differential expression analysis. Nat Methods 2014. PubMed
  • Kalaitzidis D, Scadden DT. Tic-TACs: refreshing hair growth. Cell 2014; 157:769-70. PubMed
  • Spencer JA, Ferraro F, Roussakis E, Klein A, Wu J, Runnels JM, Zaher W, Mortensen LJ, Alt C, Turcotte R, Yusuf R, Côté D, Vinogradov SA, Scadden DT, Lin CP. Direct measurement of local oxygen concentration in the bone marrow of live animals. Nature 2014; 508:269-73. PubMed
  • Schajnovitz A, Scadden DT. Bone's dark side: mutated osteoblasts implicated in leukemia. Cell Res 2014; 24:383-4. PubMed
  • Scadden DT. Nice Neighborhood: Emerging Concepts of the Stem Cell Niche. Cell 2014; 157:41-50. PubMed
  • Li X, Romain RD, Park D, Scadden DT, Merchant JL, Arnaout MA. Stress hematopoiesis is regulated by the Kr端ppel-like transcription factor ZBP-89. Stem Cells 2014; 32:791-801. PubMed
  • Morrison SJ, Scadden DT. The bone marrow niche for haematopoietic stem cells. Nature 2014; 505:327-34. PubMed
  • Park D, Spencer JA, Lin CP, Scadden DT. Sequential In vivo Imaging of Osteogenic Stem/Progenitor Cells During Fracture Repair. 2014. PubMed
  • Catic A, Suh CY, Hill CT, Daheron L, Henkel T, Orford KW, Dombkowski DM, Liu T, Liu XS, Scadden DT. Genome-wide map of nuclear protein degradation shows NCoR1 turnover as a key to mitochondrial gene regulation. Cell 2013; 155:1380-95. PubMed
  • Hartwell KA, Miller PG, Mukherjee S, Kahn AR, Stewart AL, Logan DJ, Negri JM, Duvet M, Järås M, Puram R, Dancik V, Al-Shahrour F, Kindler T, Tothova Z, Chattopadhyay S, Hasaka T, Narayan R, Dai M, Huang C, Shterental S, Chu LP, Haydu JE, Shieh JH, Steensma DP, Munoz B, Bittker JA, Shamji AF, Clemons PA, Tolliday NJ, Carpenter AE, Gilliland DG, Stern AM, Moore MA, Scadden DT, Schreiber SL, Ebert BL, Golub TR. Niche-based screening identifies small-molecule inhibitors of leukemia stem cells. Nat Chem Biol 2013; 9:840-8. PubMed
  • Silberstein L, Scadden DT. Blood scent. Cell 2013; 155:981-2. PubMed
  • Zhang H, Alberich-Jorda M, Amabile G, Yang H, Staber PB, Di Ruscio A, Diruscio A, Welner RS, Ebralidze A, Zhang J, Levantini E, Lefebvre V, Valk PJ, Delwel R, Hoogenkamp M, Nerlov C, Cammenga J, Saez B, Scadden DT, Bonifer C, Ye M, Tenen DG. Sox4 is a key oncogenic target in C/EBP留 mutant acute myeloid leukemia. Cancer Cell 2013; 24:575-88. PubMed
  • Krause DS, Fulzele K, Catic A, Sun CC, Dombkowski D, Hurley MP, Lezeau S, Attar E, Wu JY, Lin HY, Divieti-Pajevic P, Hasserjian RP, Schipani E, Van Etten RA, Scadden DT. Differential regulation of myeloid leukemias by the bone marrow microenvironment. Nat Med 2013; 19:1513-7. PubMed
  • Cutler C, Multani P, Robbins D, Kim HT, Le T, Hoggatt J, Pelus LM, Desponts C, Chen YB, Rezner B, Armand P, Koreth J, Glotzbecker B, Ho VT, Alyea E, Isom M, Kao G, Armant M, Silberstein L, Hu P, Soiffer RJ, Scadden DT, Ritz J, Goessling W, North TE, Mendlein J, Ballen K, Zon LI, Antin JH, Shoemaker DD. Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation. Blood 2013; 122:3074-81. PubMed
  • Samuel R, Daheron L, Liao S, Vardam T, Kamoun WS, Batista A, Buecker C, Schäfer R, Han X, Au P, Scadden DT, Duda DG, Fukumura D, Jain RK. Generation of functionally competent and durable engineered blood vessels from human induced pluripotent stem cells. Proc Natl Acad Sci U S A 2013; 110:12774-9. PubMed
  • Miller PG, Al-Shahrour F, Hartwell KA, Chu LP, Järås M, Puram RV, Puissant A, Callahan KP, Ashton J, McConkey ME, Poveromo LP, Cowley GS, Kharas MG, Labelle M, Shterental S, Fujisaki J, Silberstein L, Alexe G, Al-Hajj MA, Shelton CA, Armstrong SA, Root DE, Scadden DT, Hynes RO, Mukherjee S, Stegmaier K, Jordan CT, Ebert BL. In Vivo RNAi screening identifies a leukemia-specific dependence on integrin beta 3 signaling. Cancer Cell 2013; 24:45-58. PubMed
  • Roccaro AM, Sacco A, Maiso P, Azab AK, Tai YT, Reagan M, Azab F, Flores LM, Campigotto F, Weller E, Anderson KC, Scadden DT, Ghobrial IM. BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression. J Clin Invest 2013; 123:1542-55. PubMed
  • Sykes SM, Scadden DT. Modeling human hematopoietic stem cell biology in the mouse. Semin Hematol 2013; 50:92-100. PubMed
  • Pozzi S, Fulciniti M, Yan H, Vallet S, Eda H, Patel K, Santo L, Cirstea D, Hideshima T, Schirtzinge L, Kuhstoss S, Anderson KC, Munshi N, Scadden D, Kronenberg HM, Raje N. In vivo and in vitro effects of a novel anti-Dkk1 neutralizing antibody in multiple myeloma. Bone 2013; 53:487-96. PubMed
  • Hoggatt J, Mohammad KS, Singh P, Hoggatt AF, Chitteti BR, Speth JM, Hu P, Poteat BA, Stilger KN, Ferraro F, Silberstein L, Wong FK, Farag SS, Czader M, Milne GL, Breyer RM, Serezani CH, Scadden DT, Guise TA, Srour EF, Pelus LM. Differential stem- and progenitor-cell trafficking by prostaglandin E2. Nature 2013; 495:365-9. PubMed
  • Ruiz-Riol M, Mothe B, Gandhi RT, Bhardwaj N, Scadden DT, Sanchez-Merino V, Brander C. Influenza, but not HIV-specific CTL epitopes, elicits delayed-type hypersensitivity (DTH) reactions in HIV-infected patients. Eur J Immunol 2013. PubMed
  • Brown K, Xie S, Qiu X, Mohrin M, Shin J, Liu Y, Zhang D, Scadden DT, Chen D. SIRT3 reverses aging-associated degeneration. Cell Rep 2013; 3:319-27. PubMed
  • Yildirim E, Kirby JE, Brown DE, Mercier FE, Sadreyev RI, Scadden DT, Lee JT. Xist RNA is a potent suppressor of hematologic cancer in mice. Cell 2013; 152:727-42. PubMed
  • Carlson AL, Fujisaki J, Wu J, Runnels JM, Turcotte R, Spencer JA, Celso CL, Scadden DT, Strom TB, Lin CP. Correction: Tracking Single Cells in Live Animals Using a Photoconvertible Near-Infrared Cell Membrane Label. PLoS ONE 2013. PubMed
  • Carlson AL, Fujisaki J, Wu J, Runnels JM, Turcotte R, Celso CL, Scadden DT, Strom TB, Lin CP. Tracking single cells in live animals using a photoconvertible near-infrared cell membrane label. PLoS ONE 2013; 8:e69257. PubMed
  • Fulzele K, Krause DS, Panaroni C, Saini V, Barry KJ, Liu X, Lotinun S, Baron R, Bonewald L, Feng JQ, Chen M, Weinstein LS, Wu JY, Kronenberg HM, Scadden DT, Divieti Pajevic P. Myelopoiesis is regulated by osteocytes through Gs留-dependent signaling. Blood 2012. PubMed
  • van Etten RA, Mauro M, Radich JP, Goldman JM, Saglio G, Jamieson C, Soverini S, Gambacorti-Passerini C, Hehlmann R, Martinelli G, Perrotti D, Scadden DT, Skorski T, Tefferi A, Mughal TI. Advances in the biology and therapy of chronic myeloid leukemia (CML): Proceedings from the 6(th) Post-ASH International CML and Myeloproliferative Neoplasms Workshop. Leuk Lymphoma 2012. PubMed
  • Guo S, Bai H, Megyola CM, Halene S, Krause DS, Scadden DT, Lu J. Complex oncogene dependence in microRNA-125a-induced myeloproliferative neoplasms. Proc Natl Acad Sci U S A 2012; 109:16636-41. PubMed
  • Yusuf RZ, Scadden DT. Fate through Fat: Lipid Metabolism Determines Stem Cell Division Outcome. Cell Metab 2012; 16:411-3. PubMed
  • Kalaitzidis D, Sykes SM, Wang Z, Punt N, Tang Y, Ragu C, Sinha AU, Lane SW, Souza AL, Clish CB, Anastasiou D, Gilliland DG, Scadden DT, Guertin DA, Armstrong SA. mTOR complex 1 plays critical roles in hematopoiesis and Pten-loss-evoked leukemogenesis. Cell Stem Cell 2012; 11:429-39. PubMed
  • Hoggatt J, Scadden DT. The stem cell niche: tissue physiology at a single cell level. J Clin Invest 2012; 122:3029-34. PubMed
  • Demers M, Krause DS, Schatzberg D, Martinod K, Voorhees JR, Fuchs TA, Scadden DT, Wagner DD. Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis. Proc Natl Acad Sci U S A 2012; 109:13076-81. PubMed
  • Scadden DT. Rethinking stroma: lessons from the blood. Cell Stem Cell 2012; 10:648-9. PubMed
  • Yusuf RZ, Wang YH, Scadden DT. The secrets of the bone marrow niche: Metabolic priming for AML. Nat Med 2012; 18:865-7. PubMed
  • Krause DS, Scadden DT. Deconstructing the complexity of a microenvironmental niche. Cell 2012; 149:16-7. PubMed
  • Mosam A, Shaik F, Uldrick TS, Esterhuizen T, Friedland GH, Scadden DT, Aboobaker J, Coovadia HM. A randomized controlled trial of HAART versus HAART and chemotherapy in therapy-na誰ve patients with HIV-associated Kaposi sarcoma in South Africa. J Acquir Immune Defic Syndr 2012. PubMed
  • Park D, Spencer JA, Koh BI, Kobayashi T, Fujisaki J, Clemens TL, Lin CP, Kronenberg HM, Scadden DT. Endogenous Bone Marrow MSCs Are Dynamic, Fate-Restricted Participants in Bone Maintenance and Regeneration. Cell Stem Cell 2012; 10:259-72. PubMed
  • Krause DS, Scadden DT, Preffer FI. The hematopoietic stem cell niche--home for friend and foe? 2013; 84:7-20. PubMed
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