David Scadden

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi request reprint Immune reconstitution in AIDS: oncologic implications and hematologic approaches
    D T Scadden
    Massachusetts General Hospital, Dana Farber Partners Cancer Care, Harvard Medical School, Boston 02129, USA
    Curr Opin Oncol 11:503-7. 1999
  2. doi request reprint Differentiation and characterization of T cells
    Paul Robertson
    Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
    Curr Protoc Immunol . 2005
  3. ncbi request reprint Stem cells and immune reconstitution in AIDS
    David T Scadden
    Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA
    Blood Rev 17:227-31. 2003
  4. ncbi request reprint Toward cellular-based therapies for HIV infection
    David T Scadden
    Partners AIDS Research Center and MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston 02129, USA
    J Hematother Stem Cell Res 11:759-64. 2002
  5. pmc The weight of cell identity
    David T Scadden
    Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    J Clin Invest 117:3653-5. 2007
  6. pmc The stem cell niche in health and leukemic disease
    David T Scadden
    Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Best Pract Res Clin Haematol 20:19-27. 2007
  7. ncbi request reprint AIDS-related malignancies
    David T Scadden
    AIDS Research Center and Cancer Center, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Room 5212, Boston, Massachussetts 02129, USA
    Annu Rev Med 54:285-303. 2003
  8. ncbi request reprint The stem-cell niche as an entity of action
    David T Scadden
    Massachusetts General Hospital Center for Regenerative Medicine, Harvard Stem Cell Institute, 185 Cambridge Street, CPZN 4265A, Boston, Massachusetts 02114, USA
    Nature 441:1075-9. 2006
  9. ncbi request reprint Immune reconstitution in HIV infection and its relationship to cancer
    Paul Robertson
    AIDS Research Center, Massachusetts General Hospital, Harvard Medical School 149, 13th Street, Room 5212, Boston, MA 02109, USA
    Hematol Oncol Clin North Am 17:703-16, vi. 2003
  10. doi request reprint Prospects for stem cell-based therapy
    George Q Daley
    Division of Hematology Oncology, Children s Hospital Boston, Boston, MA 02115, USA
    Cell 132:544-8. 2008

Research Grants

  1. MECHANISMS OF HEMATOPOIESIS IN AIDS
    David T Scadden; Fiscal Year: 2010
  2. Stem Cell Engagement of the Niche
    David T Scadden; Fiscal Year: 2010
  3. MECHANISMS OF HEMATOPOIESIS IN AIDS
    David Scadden; Fiscal Year: 2007
  4. TARGETED MANIPULATION OF STEM CELLS FOR AIDS THERAPY
    David Scadden; Fiscal Year: 2007
  5. BOSTON AIDS MALIGNANCY CONSORTIUM
    David Scadden; Fiscal Year: 2004
  6. MECHANISMS OF HEMATOPOIESIS IN AIDS
    David Scadden; Fiscal Year: 2005
  7. FUNCTIONAL ISOLATION OF HUMAN HEMATOPOIETIC STEM CELLS
    David Scadden; Fiscal Year: 2004
  8. TARGETED MANIPULATION OF STEM CELLS FOR AIDS THERAPY
    David Scadden; Fiscal Year: 2005
  9. Dynamic interactions between stem cells and their niche.
    David Scadden; Fiscal Year: 2007
  10. TARGETED MANIPULATION OF STEM CELLS FOR AIDS THERAPY
    David T Scadden; Fiscal Year: 2010

Detail Information

Publications82

  1. ncbi request reprint Immune reconstitution in AIDS: oncologic implications and hematologic approaches
    D T Scadden
    Massachusetts General Hospital, Dana Farber Partners Cancer Care, Harvard Medical School, Boston 02129, USA
    Curr Opin Oncol 11:503-7. 1999
    ..These approaches are based on better understanding of the immunobiology of HIV and its impact on hematopoietic tissues...
  2. doi request reprint Differentiation and characterization of T cells
    Paul Robertson
    Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
    Curr Protoc Immunol . 2005
    ..In bringing together a number of existing protocols, many techniques important in investigating T cell development can be reviewed in one place...
  3. ncbi request reprint Stem cells and immune reconstitution in AIDS
    David T Scadden
    Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA
    Blood Rev 17:227-31. 2003
    ..The capability of stem cells and the thymus to restore function and their limitations in the context of HIV infection are discussed in this review...
  4. ncbi request reprint Toward cellular-based therapies for HIV infection
    David T Scadden
    Partners AIDS Research Center and MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston 02129, USA
    J Hematother Stem Cell Res 11:759-64. 2002
    ..This article will review some of the mechanisms participating in immune regeneration, the stakes involved in effectively accomplishing full reconstitution, and potential approaches to enhance the limited endogenous regenerative process...
  5. pmc The weight of cell identity
    David T Scadden
    Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    J Clin Invest 117:3653-5. 2007
    ..These cells remained true to their roots, indicating how difficult it will be to exploit cell plasticity for therapeutic purposes...
  6. pmc The stem cell niche in health and leukemic disease
    David T Scadden
    Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Best Pract Res Clin Haematol 20:19-27. 2007
    ..Studies are ongoing as to how the stem cell microenvironment can support or propagate malignancies. By understanding the signals of this particular microenvironment, we may be able to adapt them to achieve a therapeutic benefit...
  7. ncbi request reprint AIDS-related malignancies
    David T Scadden
    AIDS Research Center and Cancer Center, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Room 5212, Boston, Massachussetts 02129, USA
    Annu Rev Med 54:285-303. 2003
    ..This chapter discusses the pathophysiologic background of these tumors, how they have been affected by the use of anti-HIV medications, and their clinical management...
  8. ncbi request reprint The stem-cell niche as an entity of action
    David T Scadden
    Massachusetts General Hospital Center for Regenerative Medicine, Harvard Stem Cell Institute, 185 Cambridge Street, CPZN 4265A, Boston, Massachusetts 02114, USA
    Nature 441:1075-9. 2006
    ..The interplay between stem cells and their niche creates the dynamic system necessary for sustaining tissues, and for the ultimate design of stem-cell therapeutics...
  9. ncbi request reprint Immune reconstitution in HIV infection and its relationship to cancer
    Paul Robertson
    AIDS Research Center, Massachusetts General Hospital, Harvard Medical School 149, 13th Street, Room 5212, Boston, MA 02109, USA
    Hematol Oncol Clin North Am 17:703-16, vi. 2003
    ..This article describes the immunodeficiency caused by HIV and the response of the immune system to HAART, with specific reference to the immune response to cancers associated with HIV infection...
  10. doi request reprint Prospects for stem cell-based therapy
    George Q Daley
    Division of Hematology Oncology, Children s Hospital Boston, Boston, MA 02115, USA
    Cell 132:544-8. 2008
    ..However, a number of technical hurdles must be overcome before therapies based on pluripotent human stem cells can enter the clinic...
  11. ncbi request reprint Myeloid expression of cytochrome P450 4F3 is determined by a lineage-specific alternative promoter
    Peter Christmas
    Renal Unit, Massachusetts General Hospital and Harvard Medical School, Charlestown 02129, USA
    J Biol Chem 278:25133-42. 2003
    ..ZEB-2 interacts with C-terminal binding protein and Smads, and this would provide opportunities for integrating environmental signals in myelopoiesis and inflammation...
  12. pmc Differential CD146 expression on circulating versus tissue endothelial cells in rectal cancer patients: implications for circulating endothelial and progenitor cells as biomarkers for antiangiogenic therapy
    Dan G Duda
    Steele Laboratory for Tumor Biology, Department of Radiation Oncology and Center for Regenerative Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    J Clin Oncol 24:1449-53. 2006
    ..CD146 is considered a panendothelial-specific marker, but its utility as a CEC marker in cancer patients remains unclear...
  13. ncbi request reprint Lineage-negative side-population (SP) cells with restricted hematopoietic capacity circulate in normal human adult blood: immunophenotypic and functional characterization
    Frederic I Preffer
    Department of Pathology, Transplantation Biology Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    Stem Cells 20:417-27. 2002
    ..Thus, human blood SP cells, although rare, may serve as a source of selected leukocyte progenitor cells. The immunophenotype of circulating SP cells may provide clues to their seeding and homing capacity...
  14. ncbi request reprint Kaposi's sarcoma-associated herpesvirus-specific immune reconstitution and antiviral effect of combined HAART/chemotherapy in HIV clade C-infected individuals with Kaposi's sarcoma
    Florian Bihl
    Partners AIDS Research Center, Massachusetts General Hospital and Harvard Medical School, 13th Street, Charlestown, MA 02129, USA
    AIDS 21:1245-52. 2007
    ..Whereas the positive effects of HAART on the regression of KS have been well established, less is known about the role of herpesvirus-specific cellular immunity in disease improvement...
  15. ncbi request reprint Defective immune function of primary effusion lymphoma cells is associated with distinct KSHV gene expression profiles
    Todd J Suscovich
    Partners AIDS Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA
    Leuk Lymphoma 45:1223-38. 2004
    ..Thus, the present data suggest that distinct patterns of KSHV gene expression may be associated with particular phenotypic and functional characteristics of PEL cells, which may influence PEL pathogenesis...
  16. pmc AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients
    Tracy T Batchelor
    Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    Cancer Cell 11:83-95. 2007
    ..Our study provides insight into different mechanisms of action of this class of drugs in recurrent glioblastoma patients and suggests that the timing of combination therapy may be critical for optimizing activity against this tumor...
  17. pmc Embryonic stem cells make human T cells
    Heather E Fleming
    Center for Regenerative Medicine, Massachusetts General Hospital, and Harvard Stem Cell Institute, Boston, MA 02114, USA
    Proc Natl Acad Sci U S A 103:12213-4. 2006
  18. pmc Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo
    Mark Stroh
    E L Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 100 Blossom Street, Boston, MA 02114, USA
    Nat Med 11:678-82. 2005
    ..These examples show the versatility of quantum dots for studying tumor pathophysiology and creating avenues for treatment...
  19. pmc In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment
    Dorothy A Sipkins
    Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St, Boston, Massachusetts 02114, USA
    Nature 435:969-73. 2005
    ..Specialized vascular structures therefore appear to delineate a microenvironment with unique physiology that can be exploited by circulating malignant cells...
  20. ncbi request reprint Impact of Kaposi sarcoma-associated herpesvirus (KSHV) burden and HIV coinfection on the detection of T cell responses to KSHV ORF73 and ORF65 proteins
    Tonia Woodberry
    Partners AIDS Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Infect Dis 192:622-9. 2005
    ..These data have implications for the reliable identification of KSHV infection and may help guide the design of immune-based therapeutic and prophylactic interventions...
  21. pmc Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derived stem cells
    Jeremy S Duffield
    Renal Division and Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Clin Invest 115:1743-55. 2005
    ..It is likely that intrinsic tubular cell proliferation accounts for functionally significant replenishment of the tubular epithelium after ischemia...
  22. pmc P2Y-like receptor, GPR105 (P2Y14), identifies and mediates chemotaxis of bone-marrow hematopoietic stem cells
    Byeong Chel Lee
    Center for Regenerative Medicine and Technology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA
    Genes Dev 17:1592-604. 2003
    ..These data suggest a new class of receptors participating in the regulation of the stem cell compartment...
  23. pmc Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia
    Marc H G P Raaijmakers
    Center for Regenerative Medicine, Massachusetts General Hospital and Harvard Medical School CPZN, USA
    Nature 464:852-7. 2010
    ..Furthermore, primary stromal dysfunction can result in secondary neoplastic disease, supporting the concept of niche-induced oncogenesis...
  24. ncbi request reprint Receptor tyrosine kinase, EphB4 (HTK), accelerates differentiation of select human hematopoietic cells
    Zhengyu Wang
    Experimental Hematology, AIDS Research Center and MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA
    Blood 99:2740-7. 2002
    ..EphB4 enforces preferential megakaryocytic and erythroid differentiation and may be a molecular bridge between angiogenesis and hematopoiesis...
  25. ncbi request reprint Notch1 activation increases hematopoietic stem cell self-renewal in vivo and favors lymphoid over myeloid lineage outcome
    Sebastian Stier
    Partners AIDS Research Center, MGH Cancer Center, Massachusetts General Hospital, 149 13th Street, Boston, MA 02129, USA
    Blood 99:2369-78. 2002
    ..Notch1 offers an attractive target for stem cell manipulation strategies, particularly in the context of immunodeficiency and acquired immunodeficiency syndrome...
  26. pmc The leukemic stem cell niche: current concepts and therapeutic opportunities
    Steven W Lane
    Division of Hematology, Brigham and Women s Hospital, Boston, MA, USA
    Blood 114:1150-7. 2009
    ..Finally, we will discuss approaches for the rational development of therapies that target the microenvironment...
  27. doi request reprint Deconstructing stem cell self-renewal: genetic insights into cell-cycle regulation
    KEITH W ORFORD
    Massachusetts General Hospital, MGH Center for Regenerative Medicine, Harvard University, 185 Cambridge Street, CPZN Room 4265A, Boston, Massachusetts 02114, USA
    Nat Rev Genet 9:115-28. 2008
    ..Although the dynamics of the embryonic and adult stem cell cycles are profoundly dissimilar, we suggest that shared principles underlie the governance of this important decision point in diverse stem cell types...
  28. pmc Human HTm4 is a hematopoietic cell cycle regulator
    Jose L Donato
    Department of Medicine, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 109:51-8. 2002
    ..Overexpression of HTm4 can cause cell cycle arrest at the G(0)/G(1) phase. Thus, HTm4 is a novel hematopoietic modulator for the G(1)-S cell cycle transition...
  29. ncbi request reprint Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood
    Joshua Johnson
    Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Harvard Medical School, Boston, Massachusetts 02114, USA
    Cell 122:303-15. 2005
    ..These results identify BM as a potential source of germ cells that could sustain oocyte production in adulthood...
  30. ncbi request reprint Plasmablastic lymphoma in HIV-positive patients: an aggressive Epstein-Barr virus-associated extramedullary plasmacytic neoplasm
    Henry Y Dong
    Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Am J Surg Pathol 29:1633-41. 2005
    ..We conclude that most plasmacytic tumors in HIV-positive individuals are extramedullary, clinically aggressive EBV(+) tumors identical to plasmablastic lymphoma that does not have the clinical features of plasma cell myeloma...
  31. pmc Thymocyte emigration is mediated by active movement away from stroma-derived factors
    Mark C Poznansky
    AIDS Research Center and Massachusetts General Hospital Cancer Center, Building 149 13th Street, Room 4005A, Boston, MA 02129, USA
    J Clin Invest 109:1101-10. 2002
    ..Thymic emigration is mediated, at least in part, by specific fugetaxis-inducing factors to which only mature cells respond...
  32. ncbi request reprint Case records of the Massachusetts General Hospital. Case 30-2006. A 41-year-old man with dyspnea, fever, and lymphadenopathy
    David T Scadden
    Department of Hematology Oncology, Massachusetts General Hospital, USA
    N Engl J Med 355:1358-68. 2006
  33. pmc Forward RNAi screens in primary human hematopoietic stem/progenitor cells
    Nicole Ali
    Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Blood 113:3690-5. 2009
    ....
  34. ncbi request reprint Tumor stromal-derived factor-1 recruits vascular progenitors to mitotic neovasculature, where microenvironment influences their differentiated phenotypes
    Manish Aghi
    Program in Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
    Cancer Res 66:9054-64. 2006
    ..Although CXCR4 blockade selectively targeted endothelium generated by vasculogenesis, completely inhibiting vessel formation may require combination therapy targeting locally derived and marrow-derived endothelium...
  35. doi request reprint Analysis of the hematopoietic stem cell niche
    Cristina Lo Celso
    Massachusetts General Hospital, Boston, Massachusetts, USA
    Curr Protoc Stem Cell Biol . 2007
    ..In this unit we describe a collection of protocols spanning a wide range of techniques that can help every researcher tackling questions regarding the nature of the HSC niche...
  36. pmc Lytic and latent antigens of the human gammaherpesviruses Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus induce T-cell responses with similar functional properties and memory phenotypes
    Florian Bihl
    Partners AIDS Research Center, Massachusetts General Hospital East, 149 13th Street, Charlestown, MA 02129 2000, USA
    J Virol 81:4904-8. 2007
    ....
  37. doi request reprint Differential H3K4 methylation identifies developmentally poised hematopoietic genes
    Keith Orford
    Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Dev Cell 14:798-809. 2008
    ..These data reveal distinct epigenetic regulation of CGI and non-CGI genes during development and indicate an interactive relationship between DNA sequence and differential H3K4 methylation in lineage-specific differentiation...
  38. pmc Wnt signaling in the niche enforces hematopoietic stem cell quiescence and is necessary to preserve self-renewal in vivo
    Heather E Fleming
    Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA
    Cell Stem Cell 2:274-83. 2008
    ..Wnt pathway activation in the niche is required to limit HSC proliferation and preserve the reconstituting function of endogenous hematopoietic stem cells...
  39. pmc A protocol for phenotypic detection and enumeration of circulating endothelial cells and circulating progenitor cells in human blood
    Dan G Duda
    Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Nat Protoc 2:805-10. 2007
    ..The procedure should take 2-2.5 h, and is expected to detect 0.1-6.0% viable CECs and 0.01-0.20% CPCs within blood mononuclear cell population...
  40. pmc Tumor necrosis factor-alpha and endothelial cells modulate Notch signaling in the bone marrow microenvironment during inflammation
    Luis Fernandez
    Center of Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Mass, USA
    Exp Hematol 36:545-558. 2008
    ....
  41. ncbi request reprint Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor
    Gregor B Adams
    Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    Nature 439:599-603. 2006
    ..CaR has a function in retaining HSCs in close physical proximity to the endosteal surface and the regulatory niche components associated with it...
  42. ncbi request reprint Nervous activity in a stem cell niche
    Jonas Larsson
    Center for Regenerative Medicine, Massachusetts General Hospital, Boston, 02114, USA
    Cell 124:253-5. 2006
    ..The new findings suggest that the nervous system, which has the inherent ability to integrate information from throughout the organism, may govern the local relationship between stem cells and their niches...
  43. ncbi request reprint The cell cycle associated protein, HTm4, is expressed in differentiating cells of the hematopoietic and central nervous system in mice
    Jeffery L Kutok
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, 02115, USA
    J Mol Histol 36:77-87. 2005
    ..In addition, we observed that murine HTm4 is highly expressed in the developing and adult murine nervous system, suggesting a previously unrecognized role in central and peripheral nervous system development...
  44. pmc Haematopoietic stem cells depend on Galpha(s)-mediated signalling to engraft bone marrow
    Gregor B Adams
    Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    Nature 459:103-7. 2009
    ..Galpha(s) governs specific aspects of HSPC localization under physiological conditions in vivo and may be pharmacologically targeted to improve transplantation efficiency...
  45. pmc Osteoblastic regulation of B lymphopoiesis is mediated by Gs{alpha}-dependent signaling pathways
    JOY Y WU
    Endocrine Unit and Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA
    Proc Natl Acad Sci U S A 105:16976-81. 2008
    ....
  46. pmc Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer
    Christopher G Willett
    Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    Nat Med 10:145-7. 2004
    ..These data indicate that VEGF blockade has a direct and rapid antivascular effect in human tumors...
  47. ncbi request reprint Absence of biologically important Kaposi sarcoma-associated herpesvirus gene products and virus-specific cellular immune responses in multiple myeloma
    Christian Brander
    Partners AIDS Research Center, Massachusetts General Hospital, Charlestown, MA, USA
    Blood 100:698-700. 2002
    ..These data therefore do not show a biologically important association between ongoing KSHV infection and MM...
  48. pmc Differential in vivo potential of endothelial progenitor cells from human umbilical cord blood and adult peripheral blood to form functional long-lasting vessels
    Patrick Au
    Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Blood 111:1302-5. 2008
    ..Thus, umbilical cord blood EPCs hold great therapeutic potential, and their use should be pursued for vascular engineering...
  49. ncbi request reprint Ephrin receptor, EphB4, regulates ES cell differentiation of primitive mammalian hemangioblasts, blood, cardiomyocytes, and blood vessels
    Zhengyu Wang
    Centre of Regenerative Medicine and Technology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Blood 103:100-9. 2004
    ..We propose that modifying sensitivity to differentiation cues is a further means for ephrin receptors to contribute to tissue patterning and organization...
  50. doi request reprint The HSC niche concept has turned 31. Has our knowledge matured?
    Stefania Lymperi
    Massachusetts General Hospital, Harvard Stem Cell Institute, Harvard University, Boston, Massachusetts, USA
    Ann N Y Acad Sci 1192:12-8. 2010
    ..An understanding of how the niche participates in the maintenance of tissue homeostasis and repair offers new opportunities for the development of novel therapeutic tools...
  51. ncbi request reprint Ex vivo targeting of p21Cip1/Waf1 permits relative expansion of human hematopoietic stem cells
    Sebastian Stier
    Center for Regenerative Medicine and Technology, AIDS Research Center and Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, USA
    Blood 102:1260-6. 2003
    ..This approach may be useful for relative ex vivo human stem cell expansion...
  52. ncbi request reprint Stem cells remember their grade
    Cristina Lo Celso
    Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Stem Cell Institute, Boston, MA 02114, USA
    Cell Stem Cell 1:132-4. 2007
    ..In this issue of Cell Stem Cell, Dykstra et al. (2007) reveal stem cell gradation and the extent to which that gradation is retained in stem cell daughters of hematopoietic stem cells...
  53. pmc Hematopoietic stem cell responsiveness to exogenous signals is limited by caspase-3
    Viktor Janzen
    Center for Regenerative Medicine, Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Cell Stem Cell 2:584-94. 2008
    ..Caspase-3 contributes to stem cell quiescence, dampening specific signaling events and thereby cell responsiveness to microenvironmental stimuli...
  54. ncbi request reprint The protease inhibitor ritonavir inhibits the functional activity of the multidrug resistance related-protein 1 (MRP-1)
    Douglas P Olson
    AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    AIDS 16:1743-7. 2002
    ..Factors that modulate efflux pump function in vivo are poorly defined...
  55. pmc Primitive hematopoietic cells resist HIV-1 infection via p21
    Jielin Zhang
    Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02114, USA
    J Clin Invest 117:473-81. 2007
    ..Therefore, p21 is an endogenous cellular component in stem cells that provides a unique molecular barrier to HIV-1 infection and may explain how these cells remain an uninfected "sanctuary" in HIV disease...
  56. ncbi request reprint Stromal cell-derived factor-1/CXCR4 signaling modifies the capillary-like organization of human embryonic stem cell-derived endothelium in vitro
    Tong Chen
    Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Stem Cells 25:392-401. 2007
    ....
  57. pmc Evidence for incorporation of bone marrow-derived endothelial cells into perfused blood vessels in tumors
    Dan G Duda
    Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, COX 734, 100 Blossom St, Boston, MA 02114, USA
    Blood 107:2774-6. 2006
    ..We demonstrate that BMD-ECs incorporate in perfused tumor vessels, and that this contribution varies with organ site and mouse strain...
  58. ncbi request reprint The hematopoietic stem cell in its place
    Gregor B Adams
    Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    Nat Immunol 7:333-7. 2006
    ..The components are assembling into a more complex view of the niche and may now be amenable to examination as a system and possibly to alteration to affect outcomes in immune regeneration...
  59. ncbi request reprint Matrix metalloproteinase inhibitor COL-3 in the treatment of AIDS-related Kaposi's sarcoma: a phase I AIDS malignancy consortium study
    Mary Cianfrocca
    Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
    J Clin Oncol 20:153-9. 2002
    ..Secondary aims were to evaluate tumor response, pharmacokinetics, and changes in blood levels of MMP-2, MMP-9, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF)...
  60. pmc Activin A promotes multiple myeloma-induced osteolysis and is a promising target for myeloma bone disease
    Sonia Vallet
    Division of Hematology and Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Proc Natl Acad Sci U S A 107:5124-9. 2010
    ..Targeting activin A by a soluble decoy receptor reversed osteoblast inhibition, ameliorated MM bone disease, and inhibited tumor growth in an in vivo humanized MM model, setting the stage for testing in human clinical trials...
  61. pmc Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size
    Sebastian Stier
    Center for Regenerative Medicine and Technology, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    J Exp Med 201:1781-91. 2005
    ..Therefore, OPN is a negative regulatory element of the stem cell niche that limits the size of the stem cell pool and may provide a mechanism for restricting excess stem cell expansion under conditions of niche stimulation...
  62. doi request reprint CD133 expression defines a tumor initiating cell population in primary human ovarian cancer
    Michael D Curley
    Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Stem Cells 27:2875-83. 2009
    ..Our data indicate that CD133 expression defines a NOD/SCID tumor initiating subpopulation of cells in human ovarian cancer that may be an important target for new chemotherapeutic strategies aimed at eliminating ovarian cancer...
  63. ncbi request reprint Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a
    Viktor Janzen
    Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114, USA
    Nature 443:421-6. 2006
    ..Inhibition of p16INK4a may ameliorate the physiological impact of ageing on stem cells and thereby improve injury repair in aged tissue...
  64. pmc p27Kip1 constrains proliferation of neural progenitor cells in adult brain under homeostatic and ischemic conditions
    Jianhua Qiu
    Department of Radiology and Neurology, Stroke and Neurovascular Regulation Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA
    Stem Cells 27:920-7. 2009
    ..These new data demonstrate that p27 functions as a distinct inhibitor for NPC proliferation under homeostatic as well as ischemic conditions...
  65. ncbi request reprint Haploinsufficiency of GATA-2 perturbs adult hematopoietic stem-cell homeostasis
    Neil P Rodrigues
    Center for Regenerative Medicine and Technology, Massachusetts General Hospital, Boston, MA 02129, USA
    Blood 106:477-84. 2005
    ..Thus, GATA-2 dose regulates adult stem-cell homeostasis by affecting select aspects of stem cell function...
  66. ncbi request reprint Heterologous cells cooperate to augment stem cell migration, homing, and engraftment
    Gregor B Adams
    Partners AIDS Research Center and MGH Cancer Center, Harvard Medical School, Massachusetts General Hospital, Boston 02129, USA
    Blood 101:45-51. 2003
    ..This modification of cell migration by neighboring cells provides broad possibilities for combinatorial effects between cells of different types to influence cell localization...
  67. ncbi request reprint A phase II randomized study of HIV-specific T-cell gene therapy in subjects with undetectable plasma viremia on combination antiretroviral therapy
    Steven G Deeks
    University of California, San Francisco, California 94110, USA
    Mol Ther 5:788-97. 2002
    ..Both groups experienced a treatment-related increase in CD4(+) T-cell counts...
  68. ncbi request reprint The contribution of cytotoxic and noncytotoxic function by donor T-cells that support engraftment after allogeneic bone marrow transplantation
    Zhe Jiang
    Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida 33101, USA
    Biol Blood Marrow Transplant 8:588-96. 2002
    ..This study provides new findings concerning the role of cytotoxic function in the process of facilitating allogeneic donor BM engraftment...
  69. pmc Stem-cell ecology and stem cells in motion
    Thalia Papayannopoulou
    University of Washington, Health Sciences Building, Room K243, Box 357710, Seattle, WA 98195, USA
    Blood 111:3923-30. 2008
    ..In doing so, we will refrain from a detailed analysis of controversial data, emphasizing instead widely accepted views and some challenging novel ones...
  70. ncbi request reprint Stem cells: good, bad and reformable
    Viktor Janzen
    Nature 441:418-9. 2006
  71. ncbi request reprint Kinetic expression of platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) during embryonic stem cell differentiation
    Zong Jin Li
    State Key Laboratory of Experimental Hematology, National Research Center for Stem Cell Engineering and Technology, Institute of Hematology and Blood Disease Hospital, Tianjin 300020, PR China
    J Cell Biochem 95:559-70. 2005
    ..These results indicate a constitutive expression of PECAM-1 in undifferentiated murine ES cells and suggest a developmental role of PECAM-1 isoform changes during vasculogenesis and angiogenesis...
  72. ncbi request reprint Generic antiretroviral efficacy in AIDS-associated Kaposi's sarcoma in sub-Saharan Africa
    Anisa Mosam
    Department of Dermatology, Africa Centre for Health and Population Studies, Durban, South Africa
    AIDS 19:441-3. 2005
    ..At 52 weeks, 74% achieved an undetectable viral load of < 50 copies/ml, 86% achieved < 400 copies/ml, and a 3.1 log10 decline from baseline. Side-effects were minimal. The outcomes support the use of generic antiretroviral therapy...
  73. ncbi request reprint Angiogenesis inhibitor IM862 is ineffective against AIDS-Kaposi's sarcoma in a phase III trial, but demonstrates sustained, potent effect of highly active antiretroviral therapy: from the AIDS Malignancy Consortium and IM862 Study Team
    Ariela Noy
    Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    J Clin Oncol 23:990-8. 2005
    ..We report a 24-week, randomized, double-blinded, placebo-controlled phase III trial with the phase II dose, 5 mg intranasally every other day...
  74. ncbi request reprint Cancer stem cells refined
    David T Scadden
    Nat Immunol 5:701-3. 2004
  75. pmc A microenvironment-induced myeloproliferative syndrome caused by retinoic acid receptor gamma deficiency
    Carl R Walkley
    Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia
    Cell 129:1097-110. 2007
    ..These data show that loss of RARgamma results in a nonhematopoietic cell-intrinsic MPS, revealing the capability of the microenvironment to be the sole cause of hematopoietic disorders...
  76. ncbi request reprint CXCR4 and CCR5 mediate homing of primitive bone marrow-derived hematopoietic cells to the postnatal thymus
    Paul Robertson
    Center for Regenerative Medicine and Technology, Massachusetts General Hospital and Harvard Medical School, Boston MA 02114, USA
    Exp Hematol 34:308-19. 2006
    ....
  77. pmc MicroRNA-mediated control of cell fate in megakaryocyte-erythrocyte progenitors
    Jun Lu
    Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
    Dev Cell 14:843-53. 2008
    ..These experiments show that miR-150 regulates MEP fate, and thus establish a role for miRNAs in lineage specification of mammalian multipotent cells...
  78. ncbi request reprint In vivo self-renewing divisions of haematopoietic stem cells are increased in the absence of the early G1-phase inhibitor, p18INK4C
    Youzhong Yuan
    University of Pittsburgh Cancer Institute and Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh PA 15213, USA
    Nat Cell Biol 6:436-42. 2004
    ....
  79. ncbi request reprint Antitumor activity of oral 9-cis-retinoic acid in HIV-associated Kaposi's sarcoma
    Steven A Miles
    AIDS Malignancy Consortium Operations Center, University of Alabama at Birmingham, 2001 Third Avenue South, Room 1078, Birmingham, AL 35223, USA
    AIDS 16:421-9. 2002
    ..To assess the efficacy, safety and tolerance of oral 9-cis-retinoic acid in HIV-infected patients with Kaposi's sarcoma...
  80. ncbi request reprint Multiple measures of HIV burden in blood and tissue are correlated with each other but not with clinical parameters in aviremic subjects
    Peter A Anton
    University of California, Los Angeles, the San Francisco General Hospital, San Francisco, California, USA
    AIDS 17:53-63. 2003
    ..To determine the levels of residual HIV DNA and RNA in blood and gut reservoirs in aviremic patients, assess correlations among compartmental measurements of HIV burden, and evaluate association with clinical parameters...
  81. ncbi request reprint Osteoclasts eat stem cells out of house and home
    Louise E Purton
    Nat Med 12:610-1. 2006
  82. ncbi request reprint Multicenter trial of low-dose paclitaxel in patients with advanced AIDS-related Kaposi sarcoma
    Anil Tulpule
    Division of Hematology, Department of Medicine, Kenneth Norris Cancer Hospital and Research Institute, University of Southern California School of Medicine, Los Angeles, California, USA
    Cancer 95:147-54. 2002
    ..This study was performed to assess the safety and efficacy of a novel dose and schedule of paclitaxel in patients with AIDS-KS who failed to respond to previous systemic chemotherapy...

Research Grants46

  1. MECHANISMS OF HEMATOPOIESIS IN AIDS
    David T Scadden; Fiscal Year: 2010
    ..If successful, they will lead to increased engraftment efficiency of stem cells, a parameter critical for advancing stem cell therapies in blood diseases and cancer, including gene modified stem cells for AIDS. ..
  2. Stem Cell Engagement of the Niche
    David T Scadden; Fiscal Year: 2010
    ..We will use a unique combination of mouse and zebrafish model systems examined by molecular, chemical and imaging techniques. ..
  3. MECHANISMS OF HEMATOPOIESIS IN AIDS
    David Scadden; Fiscal Year: 2007
    ..If successful, they will lead to increased engraftment efficiency of stem cells, a parameter critical for advancing stem cell therapies in blood diseases and cancer, including gene modified stem cells for AIDS. ..
  4. TARGETED MANIPULATION OF STEM CELLS FOR AIDS THERAPY
    David Scadden; Fiscal Year: 2007
    ..Success of this project will provide both in depth understanding of key regulatory pathways for adult HSC and create targeted approaches to manipulate stem cell self-renewal for therapeutic purposes. ..
  5. BOSTON AIDS MALIGNANCY CONSORTIUM
    David Scadden; Fiscal Year: 2004
    ..Furthering the efforts of the BAMC within the national consortium is the focus of this proposal. ..
  6. MECHANISMS OF HEMATOPOIESIS IN AIDS
    David Scadden; Fiscal Year: 2005
    ..3. Define a role for fugetaxis in a pathologic state. We will test the potential for active T cell movement away from a fugetactic signal to participate in the pathophysiology of HIV disease. ..
  7. FUNCTIONAL ISOLATION OF HUMAN HEMATOPOIETIC STEM CELLS
    David Scadden; Fiscal Year: 2004
    ..2. Purify and clone the ligand for SC-GPR1. 3. Determine the mechanism by which ectopic expression of SC-GPR1 induces or maintains a primitive phenotype. ..
  8. TARGETED MANIPULATION OF STEM CELLS FOR AIDS THERAPY
    David Scadden; Fiscal Year: 2005
    ..Accomplishment of these aims will guide specific strategies for stem cell gene therapy of HIV disease based on principles of stem cell regulation. ..
  9. Dynamic interactions between stem cells and their niche.
    David Scadden; Fiscal Year: 2007
    ..If successful, these studies will define a novel molecular target to influence the function of stem cells in settings of marrow injury. ..
  10. TARGETED MANIPULATION OF STEM CELLS FOR AIDS THERAPY
    David T Scadden; Fiscal Year: 2010
    ..Success of this project will provide both in depth understanding of key regulatory pathways for adult HSC and create targeted approaches to manipulate stem cell self-renewal for therapeutic purposes. ..
  11. Dynamic interactions between stem cells and their niche.
    David T Scadden; Fiscal Year: 2010
    ..If successful, these studies will define a novel molecular target to influence the function of stem cells in settings of marrow injury. ..
  12. MECHANISMS OF HEMATOPOIESIS IN AIDS
    David Scadden; Fiscal Year: 2000
    ..Second, the investigator will examine the expression of gene products that regulate hematopoiesis. Third, the investigator will examine the effects of AIDS medications on T cell production. ..
  13. FUNCTIONAL ISOLATION OF HUMAN HEMATOPOIETIC STEM CELLS
    David Scadden; Fiscal Year: 1999
    ..New methods of subtraction will be developed in the laboratory in order to accomplish this aim. ..