Ann Marshak-Rothstein

Summary

Affiliation: Boston University
Country: USA

Publications

  1. ncbi Toll-like receptors in systemic autoimmune disease
    Ann Marshak-Rothstein
    Department of Microbiology, Boston University School of Medicine, 80 East Concord Street, Boston, Massachusetts 02118, USA
    Nat Rev Immunol 6:823-35. 2006
  2. pmc RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement
    Christina M Lau
    Department of Microbiology, Boston University School of Medicine, MA 02118, USA
    J Exp Med 202:1171-7. 2005
  3. pmc DNA-like class R inhibitory oligonucleotides (INH-ODNs) preferentially block autoantigen-induced B-cell and dendritic cell activation in vitro and autoantibody production in lupus-prone MRL-Fas(lpr/lpr) mice in vivo
    Petar Lenert
    Department of Internal Medicine and Pathology, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA
    Arthritis Res Ther 11:R79. 2009
  4. ncbi Immunologically active autoantigens: the role of toll-like receptors in the development of chronic inflammatory disease
    Ann Marshak-Rothstein
    Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    Annu Rev Immunol 25:419-41. 2007
  5. ncbi Comparison of CpG s-ODNs, chromatin immune complexes, and dsDNA fragment immune complexes in the TLR9-dependent activation of rheumatoid factor B cells
    Ann Marshak-Rothstein
    Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA
    J Endotoxin Res 10:247-51. 2004
  6. ncbi The stimulation of Toll-like receptors by nuclear antigens: a link between apoptosis and autoimmunity
    Ann Marshak-Rothstein
    Department of Microbiology, Boston University School of Medicine, 80 East Concord Street, Boston, MA 02118, USA
    Rheum Dis Clin North Am 30:559-74, ix. 2004
  7. ncbi Membrane Fas ligand activates innate immunity and terminates ocular immune privilege
    Meredith S Gregory
    Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA
    J Immunol 169:2727-35. 2002
  8. ncbi Toll-like receptors and activation of autoreactive B cells
    Elizabeth A Leadbetter
    Department of Microbiology, Boston University School of Medicine, Boston, Mass, USA
    Curr Dir Autoimmun 6:105-22. 2003
  9. pmc Toll-like receptor 9-dependent and -independent dendritic cell activation by chromatin-immunoglobulin G complexes
    Melissa W Boulé
    Renal Section, Department of Medicine, Boston University School of Medicine, EBRC 5th Floor, 650 Albany Street, Boston, MA 02118, USA
    J Exp Med 199:1631-40. 2004
  10. pmc Autoreactive B cells discriminate CpG-rich and CpG-poor DNA and this response is modulated by IFN-alpha
    Melissa B Uccellini
    Department of Microbiology and Immunology Training Program, Boston University School of Medicine, Boston, MA 02118, USA
    J Immunol 181:5875-84. 2008

Research Grants

  1. Immunological Mechanisms in Systemic Autoimmune Disease
    Ann Marshak Rothstein; Fiscal Year: 2009
  2. B CELL HYPERACTIVITY IN AUTOIMMUNITY
    Ann Marshak Rothstein; Fiscal Year: 2007
  3. B CELL HYPERACTIVITY IN AUTOIMMUNITY
    Ann Marshak Rothstein; Fiscal Year: 1993
  4. B CELL HYPERACTIVITY IN AUTOIMMUNITY
    Ann Marshak Rothstein; Fiscal Year: 2002
  5. B CELL HYPERACTIVITY IN AUTOIMMUNITY
    Ann Marshak Rothstein; Fiscal Year: 2003
  6. TLR/BCR Synergy in an Autoreactive B Cell Activation
    Ann Marshak Rothstein; Fiscal Year: 2003
  7. B CELL HYPERACTIVITY IN AUTOIMMUNITY
    Ann Marshak Rothstein; Fiscal Year: 2004
  8. B CELL HYPERACTIVITY IN AUTOIMMUNITY
    Ann Marshak Rothstein; Fiscal Year: 2005
  9. B CELL HYPERACTIVITY IN AUTOIMMUNITY
    Ann Marshak Rothstein; Fiscal Year: 2009
  10. B CELL HYPERACTIVITY IN AUTOIMMUNITY
    Ann Marshak Rothstein; Fiscal Year: 2001

Collaborators

Detail Information

Publications40

  1. ncbi Toll-like receptors in systemic autoimmune disease
    Ann Marshak-Rothstein
    Department of Microbiology, Boston University School of Medicine, 80 East Concord Street, Boston, Massachusetts 02118, USA
    Nat Rev Immunol 6:823-35. 2006
    ....
  2. pmc RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement
    Christina M Lau
    Department of Microbiology, Boston University School of Medicine, MA 02118, USA
    J Exp Med 202:1171-7. 2005
    ..As further evidence that TLRs play a key role in autoantibody responses in SLE, we found that autoimmune-prone mice, lacking the TLR adaptor protein MyD88, had markedly reduced chromatin, Sm, and rheumatoid factor autoantibody titers...
  3. pmc DNA-like class R inhibitory oligonucleotides (INH-ODNs) preferentially block autoantigen-induced B-cell and dendritic cell activation in vitro and autoantibody production in lupus-prone MRL-Fas(lpr/lpr) mice in vivo
    Petar Lenert
    Department of Internal Medicine and Pathology, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA
    Arthritis Res Ther 11:R79. 2009
    ..Thus, strategies to preferentially block innate activation through TLRs in autoimmune B cells may be preferred over non-selective B-cell depletion...
  4. ncbi Immunologically active autoantigens: the role of toll-like receptors in the development of chronic inflammatory disease
    Ann Marshak-Rothstein
    Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    Annu Rev Immunol 25:419-41. 2007
    ..In this context, they likely play a key role in the development of systemic autoimmune diseases...
  5. ncbi Comparison of CpG s-ODNs, chromatin immune complexes, and dsDNA fragment immune complexes in the TLR9-dependent activation of rheumatoid factor B cells
    Ann Marshak-Rothstein
    Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA
    J Endotoxin Res 10:247-51. 2004
    ..These data have important implications regarding the therapeutic application of TLR9 inhibitors to the treatment of systemic autoimmune diseases...
  6. ncbi The stimulation of Toll-like receptors by nuclear antigens: a link between apoptosis and autoimmunity
    Ann Marshak-Rothstein
    Department of Microbiology, Boston University School of Medicine, 80 East Concord Street, Boston, MA 02118, USA
    Rheum Dis Clin North Am 30:559-74, ix. 2004
    ..In the case of antinuclear antibodies, it seems that DNA itself can serve as an endogenous adjuvant. Similar to many of the microbial adjuvants, mammalian DNA mediates its effect through a Toll-like receptor--in this case, TLR9...
  7. ncbi Membrane Fas ligand activates innate immunity and terminates ocular immune privilege
    Meredith S Gregory
    Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA
    J Immunol 169:2727-35. 2002
    ..In conclusion, our data indicate that the function of FasL on intraocular tumors is determined by the microenvironment in conjunction with the form and level of FasL expressed...
  8. ncbi Toll-like receptors and activation of autoreactive B cells
    Elizabeth A Leadbetter
    Department of Microbiology, Boston University School of Medicine, Boston, Mass, USA
    Curr Dir Autoimmun 6:105-22. 2003
  9. pmc Toll-like receptor 9-dependent and -independent dendritic cell activation by chromatin-immunoglobulin G complexes
    Melissa W Boulé
    Renal Section, Department of Medicine, Boston University School of Medicine, EBRC 5th Floor, 650 Albany Street, Boston, MA 02118, USA
    J Exp Med 199:1631-40. 2004
    ..The data establish a critical role for self-antigen in DC activation and explain how the innate immune system might drive the adaptive immune response in SLE...
  10. pmc Autoreactive B cells discriminate CpG-rich and CpG-poor DNA and this response is modulated by IFN-alpha
    Melissa B Uccellini
    Department of Microbiology and Immunology Training Program, Boston University School of Medicine, Boston, MA 02118, USA
    J Immunol 181:5875-84. 2008
    ....
  11. ncbi DNA and RNA autoantigens as autoadjuvants
    Liliana Busconi
    Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA
    J Endotoxin Res 12:379-84. 2006
    ..The data demonstrate that only certain nucleic acid sequences or structures can induce autoreactive B-cell proliferation, even when delivery to the appropriate TLR compartment is facilitated by uptake through the B-cell receptor (BCR)...
  12. ncbi Murine dendritic cell type I IFN production induced by human IgG-RNA immune complexes is IFN regulatory factor (IRF)5 and IRF7 dependent and is required for IL-6 production
    Kei Yasuda
    Renal Section, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
    J Immunol 178:6876-85. 2007
    ..This system may also prove useful for the study of receptors and signaling pathways used by immune complexes in other human diseases...
  13. pmc IFN regulatory factor 5 is required for disease development in the FcgammaRIIB-/-Yaa and FcgammaRIIB-/- mouse models of systemic lupus erythematosus
    Christophe Richez
    Renal Section, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
    J Immunol 184:796-806. 2010
    ..Overall, we demonstrate that IRF5 plays an essential role in lupus pathogenesis in murine models and that this is mediated through pathways beyond that of type I IFN production...
  14. pmc RAGE-independent autoreactive B cell activation in response to chromatin and HMGB1/DNA immune complexes
    Ana M Avalos
    Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA
    Autoimmunity 43:103-10. 2010
    ..We found that spontaneous and defined DNA ICs activated RAGE+ and RAGE(- ) AM14 B cells to a comparable extent. These results suggest that HMGB1 promotes B cell responses to endogenous TLR9 ligands through a RAGE-independent mechanism...
  15. ncbi Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors
    Elizabeth A Leadbetter
    Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    Nature 416:603-7. 2002
    ..The unique features of this dual-engagement pathway should facilitate the development of therapies that specifically target autoreactive B cells...
  16. pmc Differential cytokine production and bystander activation of autoreactive B cells in response to CpG-A and CpG-B oligonucleotides
    Ana M Avalos
    Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA
    J Immunol 183:6262-8. 2009
    ..These data identify direct and indirect mechanisms by which BCR engagement facilitates access of exogenous ligands to TLR9-associated compartments and subsequent B cell activation...
  17. pmc Requirement for DNA CpG content in TLR9-dependent dendritic cell activation induced by DNA-containing immune complexes
    Kei Yasuda
    Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
    J Immunol 183:3109-17. 2009
    ....
  18. pmc FcγRIIB regulation of BCR/TLR-dependent autoreactive B-cell responses
    Ana M Avalos
    Department of Microbiology, Boston University School of Medicine, Boston, MA 01655, USA
    Eur J Immunol 40:2692-8. 2010
    ..These results demonstrate that FcγRIIB can effectively modulate both BCR/TLR9 and BCR/TLR7 endosomal-dependent activation of autoreactive B cells...
  19. ncbi Functional outcome of B cell activation by chromatin immune complex engagement of the B cell receptor and TLR9
    Liliana Busconi
    Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA
    J Immunol 179:7397-405. 2007
    ..These data indicate that autoreactive B cells, stimulated by a combination of BCR and TLR9 ligands, acquire functional properties that may contribute to the activation of additional cells involved in the autoimmune disease process...
  20. ncbi B cells and dendritic cells from V kappa 8 light chain transgenic mice activate MRL-lpr/gld CD4+ T cells
    Britte C Beaudette-Zlatanova
    Renal Section, Department of Medicine, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, USA
    J Immunol 177:45-52. 2006
    ..Additionally, although the precise nature of the neoantigen is not known, the T cells described in this report may provide a useful tool for examining the role of T cells in the RF autoantibody response...
  21. doi Toll-like receptor-dependent immune complex activation of B cells and dendritic cells
    Melissa B Uccellini
    Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA
    Methods Mol Biol 517:363-80. 2009
    ..These reagents reveal an important role for nucleic acid sequence, even when the ligand is mammalian DNA...
  22. pmc Murine B cell response to TLR7 ligands depends on an IFN-beta feedback loop
    Nathaniel M Green
    Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA
    J Immunol 183:1569-76. 2009
    ..These results highlight subtle differences in the IFN dependence of TLR7 responses compared with other TLR-mediated B cell responses...
  23. ncbi A novel signaling mechanism for soluble CD95 ligand. Synergy with anti-CD95 monoclonal antibodies for apoptosis and NF-kappaB nuclear translocation
    Sheng Xiao
    Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    J Biol Chem 277:50907-13. 2002
    ..Membrane-bound FasL induces powerful Fas-mediated signals because it possesses both Fas-focusing and signal-transducing functions...
  24. pmc Activation of autoreactive B cells by endogenous TLR7 and TLR3 RNA ligands
    Nathaniel M Green
    Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    J Biol Chem 287:39789-99. 2012
    ..These results identify parameters that define specific mammalian RNAs as ligands for TLRs...
  25. ncbi Activation of autoreactive B cells by CpG dsDNA
    Gregory A Viglianti
    Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA
    Immunity 19:837-47. 2003
    ....
  26. ncbi Control of ocular tumor growth and metastatic spread by soluble and membrane Fas ligand
    Meredith S Gregory
    The Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA
    Cancer Res 67:11951-8. 2007
    ..We conclude that the fate of FasL-expressing tumors is determined by a combination of the following: (a) the relative proportion of membrane and sFasL, and (b) the local environment that determines the extent of FasL cleavage...
  27. ncbi Toll-like receptors, endogenous ligands, and systemic autoimmune disease
    Ian R Rifkin
    Department of Medicine, Renal Section, Boston University School of Medicine, Boston, MA 02118, USA
    Immunol Rev 204:27-42. 2005
    ..However, the precise details of the interactions and the extent to which they may contribute to the pathogenesis of human disease remain to be clarified...
  28. pmc Poly(I:C) drives type I IFN- and TGFβ-mediated inflammation and dermal fibrosis simulating altered gene expression in systemic sclerosis
    Giuseppina A Farina
    Rheumatology Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
    J Invest Dermatol 130:2583-93. 2010
    ..These results suggest that TLR agonists may be important stimuli of dermal fibrosis, which is potentially mediated by TLR3 or other innate immune receptors...
  29. ncbi Changes in sensitivity of peripheral lymphocytes of autoimmune gld mice to FasL-mediated apoptosis reveal a mechanism for the preferential deletion of CD4-CD8-B220+ T cells
    Sheng Xiao
    Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02118, USA
    Int Immunol 16:759-66. 2004
    ....
  30. pmc Selective binding of anti-DNA antibodies to native dsDNA fragments of differing sequence
    Melissa B Uccellini
    Department of Microbiology, Boston University School of Medicine, Boston, MA, USA
    Immunol Lett 143:85-91. 2012
    ....
  31. pmc Regulation of autoreactive B cell responses to endogenous TLR ligands
    Ana Maria Avalos
    Department of Microbiology, Boston University School of Medicine, Boston, MA 01655, USA
    Autoimmunity 43:76-83. 2010
    ..In this context, autoreactive B cells can respond robustly to common autoantigens. These findings have important implications for the role of B cells in vivo in the pathology of SLE...
  32. pmc Phenotype and function of B cells and dendritic cells from interferon regulatory factor 5-deficient mice with and without a mutation in DOCK2
    Kei Yasuda
    Department of Medicine, Renal Section, Boston University School of Medicine, Boston, MA 02118, USA
    Int Immunol 25:295-306. 2013
    ..Overall, these studies help clarify the function of IRF5 in B cells and DCs in the absence of the DOCK2 mutation. In addition, the PCR described will be useful for other investigators using the IRF5 (-/-) mouse line...
  33. pmc Toll-like receptor driven B cell activation in the induction of systemic autoimmunity
    Nathaniel M Green
    Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA
    Semin Immunol 23:106-12. 2011
    ..Further understanding of the role of specific receptors, cell subsets, and inhibitory signals that govern these TLR-associated pathways will enable future therapeutics to be tailored to specific categories of autoimmune disease...
  34. pmc Opposing roles for membrane bound and soluble Fas ligand in glaucoma-associated retinal ganglion cell death
    Meredith S Gregory
    Department of Ophthalmology, The Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 6:e17659. 2011
    ..By contrast, FasL-deficiency, or administration of soluble FasL, protected RGCs from cell death. These data identify membrane-bound FasL as a critical effector molecule and potential therapeutic target in glaucoma...
  35. ncbi Activation-induced cell death limits effector function of CD4 tumor-specific T cells
    Rebecca R Saff
    Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA
    J Immunol 172:6598-606. 2004
    ....
  36. ncbi A novel treatment for ocular tumors using membrane FasL vesicles to activate innate immunity and terminate immune privilege
    Meredith S Gregory
    Schepens Eye Research Institute, Boston, MA 02114, USA
    Invest Ophthalmol Vis Sci 46:2495-502. 2005
    ....
  37. ncbi Fas-ligand--iron fist or Achilles' heel?
    Andreas M Hohlbaum
    Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    Clin Immunol 103:1-6. 2002
    ..Discussed here are the experimental situations, possible mechanisms, and pathways that mediate this response...
  38. pmc Toll-like receptors and innate immune responses in systemic lupus erythematosus
    Robert Lafyatis
    Boston University School of Medicine, Department of Medicine, Rheumatology Section, 715 Albany Street, Boston, Massachusetts 02118, USA
    Arthritis Res Ther 9:222. 2007
    ..The development of clinical trials using therapeutic agents that target components of the innate immune system suggests that these advances may soon culminate in new medications for treating patients with systemic lupus erythematosus...
  39. ncbi Tolling for autoimmunity-prime time for 7
    Ann Marshak-Rothstein
    Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02215, USA
    Immunity 25:397-9. 2006
    ..Two papers in this issue of Immunity provide important insights into the contribution of Toll-like receptors in systemic autoimmune disease (Berland et al., 2006; Christensen et al., 2006)...

Research Grants26

  1. Immunological Mechanisms in Systemic Autoimmune Disease
    Ann Marshak Rothstein; Fiscal Year: 2009
    ..This study could lead to significant insights into the factors that trigger the development of SSc and strategies that might prove useful in limiting the progression of disease in afflicted patients. ..
  2. B CELL HYPERACTIVITY IN AUTOIMMUNITY
    Ann Marshak Rothstein; Fiscal Year: 2007
    ..A better understanding of the events that contribute to the initial activation of these autoreactive B cells will be critical to the development of more effective and less toxic therapies. ..
  3. B CELL HYPERACTIVITY IN AUTOIMMUNITY
    Ann Marshak Rothstein; Fiscal Year: 1993
    ..The results of this proposal should eventually have clinical application with regard to the control of the basic immunoregulatory defects involved in autoimmune disorders such as systemic lupus erythematosus and rheumatoid arthritis...
  4. B CELL HYPERACTIVITY IN AUTOIMMUNITY
    Ann Marshak Rothstein; Fiscal Year: 2002
    ..Moreover, this experimental strategy should also have direct relevance to human clinical syndromes associated with excessive RF production. ..
  5. B CELL HYPERACTIVITY IN AUTOIMMUNITY
    Ann Marshak Rothstein; Fiscal Year: 2003
    ..Moreover, this experimental strategy should also have direct relevance to human clinical syndromes associated with excessive RF production. ..
  6. TLR/BCR Synergy in an Autoreactive B Cell Activation
    Ann Marshak Rothstein; Fiscal Year: 2003
    ..The results of the studies will provide important information regarding the development of novel therapies for the treatment of systemic diseases such as SLE. ..
  7. B CELL HYPERACTIVITY IN AUTOIMMUNITY
    Ann Marshak Rothstein; Fiscal Year: 2004
    ..Moreover, this experimental strategy should also have direct relevance to human clinical syndromes associated with excessive RF production. ..
  8. B CELL HYPERACTIVITY IN AUTOIMMUNITY
    Ann Marshak Rothstein; Fiscal Year: 2005
    ..Moreover, this experimental strategy should also have direct relevance to human clinical syndromes associated with excessive RF production. ..
  9. B CELL HYPERACTIVITY IN AUTOIMMUNITY
    Ann Marshak Rothstein; Fiscal Year: 2009
    ..A better understanding of the events that contribute to the initial activation of these autoreactive B cells will be critical to the development of more effective and less toxic therapies. ..
  10. B CELL HYPERACTIVITY IN AUTOIMMUNITY
    Ann Marshak Rothstein; Fiscal Year: 2001
    ..Moreover, this experimental strategy should also have direct relevance to human clinical syndromes associated with excessive RF production. ..
  11. B CELL HYPERACTIVITY IN AUTOIMMUNITY
    Ann Marshak Rothstein; Fiscal Year: 1992
    ..The results of this proposal should eventually have clinical application with regard to the control of the basic immunoregulatory defects involved in autoimmune disorders such as systemic lupus erythematosus and rheumatoid arthritis...
  12. B CELL HYPERACTIVITY IN AUTOIMMUNITY
    Ann Marshak Rothstein; Fiscal Year: 1999
    ..The better understanding of the etiology of autoimmunity gained from these studies should be directly applicable to the treatment of human disease. ..
  13. B CELL HYPERACTIVITY IN AUTOIMMUNITY
    Ann Marshak Rothstein; Fiscal Year: 2006
    ..A better understanding of the events that contribute to the initial activation of these autoreactive B cells will be critical to the development of more effective and less toxic therapies. ..
  14. Research Program in Immunology
    Ann Marshak Rothstein; Fiscal Year: 2007
    ....
  15. B CELL HYPERACTIVITY IN AUTOIMMUNITY
    Ann Marshak Rothstein; Fiscal Year: 1990
    ..The results of this proposal should eventually have clinical application with regard to the control of the basic immunoregulatory defects involved in autoimmune disorders such as systemic lupus erythematosus and rheumatoid arthritis...
  16. B CELL HYPERACTIVITY IN AUTOIMMUNITY
    Ann Marshak Rothstein; Fiscal Year: 1991
    ..The results of this proposal should eventually have clinical application with regard to the control of the basic immunoregulatory defects involved in autoimmune disorders such as systemic lupus erythematosus and rheumatoid arthritis...