George Tsokos

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi request reprint Immune cell signaling and gene transcription in human lupus: the time has come
    George C Tsokos
    WR AIR, Silver Spring, Maryland 20910, USA
    Int Rev Immunol 23:221-4. 2004
  2. doi request reprint Inhibition of Syk activity by R788 in platelets prevents remote lung tissue damage after mesenteric ischemia-reperfusion injury
    Peter H Lapchak
    Rheumatology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA
    Am J Physiol Gastrointest Liver Physiol 302:G1416-22. 2012
  3. doi request reprint Platelets orchestrate remote tissue damage after mesenteric ischemia-reperfusion
    Peter H Lapchak
    Rheumatology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA
    Am J Physiol Gastrointest Liver Physiol 302:G888-97. 2012
  4. pmc Decay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury
    Ying Wang
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
    J Neuroinflammation 7:24. 2010
  5. pmc Abnormalities of T cell signaling in systemic lupus erythematosus
    Vaishali R Moulton
    Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    Arthritis Res Ther 13:207. 2011
  6. pmc Spleen tyrosine kinase inhibition in the treatment of autoimmune, allergic and autoinflammatory diseases
    Omer N Pamuk
    Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS 928, Boston, MA 02115, USA
    Arthritis Res Ther 12:222. 2010
  7. doi request reprint Depletion of gut commensal bacteria attenuates intestinal ischemia/reperfusion injury
    Kazuhisa Yoshiya
    Rheumatology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA
    Am J Physiol Gastrointest Liver Physiol 301:G1020-30. 2011
  8. ncbi request reprint Alterations in lipid raft composition and dynamics contribute to abnormal T cell responses in systemic lupus erythematosus
    Sandeep Krishnan
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
    J Immunol 172:7821-31. 2004
  9. pmc Syk kinase as a treatment target for therapy in autoimmune diseases
    Vasileios C Kyttaris
    Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Harvard Institutes of Medicine, HIM 238, 4 Blackfan Circle, Boston, MA 02115, USA
    Clin Immunol 124:235-7. 2007
  10. ncbi request reprint Complement, natural antibodies, autoantibodies and tissue injury
    Sherry D Fleming
    Division of Biology, Kansas State University, Manhattan, KS 66506, USA
    Autoimmun Rev 5:89-92. 2006

Research Grants

  1. CIS School on Systemic Autoimmune Diseases
    George Tsokos; Fiscal Year: 2006
  2. LYMPHOCYTE SIGNALING DEFECTS IN PATIENTS WITH LUPUS
    George Tsokos; Fiscal Year: 2007
  3. Phosphatases in Human Lupus
    George Tsokos; Fiscal Year: 2007
  4. CIS School on Systemic Autoimmune Diseases
    George Tsokos; Fiscal Year: 2007
  5. Gene Transcription in SLE
    George Tsokos; Fiscal Year: 2006
  6. Gene Transcription in SLE
    George Tsokos; Fiscal Year: 2009
  7. LYMPHOCYTE SIGNALING DEFECTS IN PATIENTS WITH LUPUS
    George Tsokos; Fiscal Year: 2009
  8. Gene Transcription in SLE
    George C Tsokos; Fiscal Year: 2010
  9. Phosphatases in Human Lupus
    George C Tsokos; Fiscal Year: 2010
  10. Expanded double negative T cells in SLE
    George C Tsokos; Fiscal Year: 2010

Collaborators

Detail Information

Publications68

  1. ncbi request reprint Immune cell signaling and gene transcription in human lupus: the time has come
    George C Tsokos
    WR AIR, Silver Spring, Maryland 20910, USA
    Int Rev Immunol 23:221-4. 2004
  2. doi request reprint Inhibition of Syk activity by R788 in platelets prevents remote lung tissue damage after mesenteric ischemia-reperfusion injury
    Peter H Lapchak
    Rheumatology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA
    Am J Physiol Gastrointest Liver Physiol 302:G1416-22. 2012
    ..The use of small-molecule inhibitors may be valuable to prevent tissue damage in remote organs following I/R injury...
  3. doi request reprint Platelets orchestrate remote tissue damage after mesenteric ischemia-reperfusion
    Peter H Lapchak
    Rheumatology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA
    Am J Physiol Gastrointest Liver Physiol 302:G888-97. 2012
    ....
  4. pmc Decay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury
    Ying Wang
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
    J Neuroinflammation 7:24. 2010
    ..The present study investigates the ability of DAF to protect primary cultured neuronal cells subjected to sodium cyanide (NaCN)-induced hypoxia from degeneration and apoptosis...
  5. pmc Abnormalities of T cell signaling in systemic lupus erythematosus
    Vaishali R Moulton
    Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    Arthritis Res Ther 13:207. 2011
    ..Study of signaling and gene transcription abnormalities in SLE T cells has led to the identification of novel targets for therapy...
  6. pmc Spleen tyrosine kinase inhibition in the treatment of autoimmune, allergic and autoinflammatory diseases
    Omer N Pamuk
    Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS 928, Boston, MA 02115, USA
    Arthritis Res Ther 12:222. 2010
    ..While the extent and severity of side effects appear to be limited so far, larger studies will unravel the risk involved with the clinical benefit...
  7. doi request reprint Depletion of gut commensal bacteria attenuates intestinal ischemia/reperfusion injury
    Kazuhisa Yoshiya
    Rheumatology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA
    Am J Physiol Gastrointest Liver Physiol 301:G1020-30. 2011
    ..These results suggest that depletion of gut commensal bacteria decreases B cells, Igs, and TLR expression in the intestine, inhibits complement activation, and attenuates intestinal inflammation and injury following M I/R...
  8. ncbi request reprint Alterations in lipid raft composition and dynamics contribute to abnormal T cell responses in systemic lupus erythematosus
    Sandeep Krishnan
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
    J Immunol 172:7821-31. 2004
    ..Thus, we propose that alterations in the lipid raft signaling machinery represent an important mechanism that is responsible for the heightened and accelerated T cell responses in SLE...
  9. pmc Syk kinase as a treatment target for therapy in autoimmune diseases
    Vasileios C Kyttaris
    Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Harvard Institutes of Medicine, HIM 238, 4 Blackfan Circle, Boston, MA 02115, USA
    Clin Immunol 124:235-7. 2007
    ..Syk initiates intracellular signaling once the receptor is engaged by its ligand. Blocking Syk may prove beneficial in interrupting the propagation of the abnormal immune response in both autoimmune and allergic diseases...
  10. ncbi request reprint Complement, natural antibodies, autoantibodies and tissue injury
    Sherry D Fleming
    Division of Biology, Kansas State University, Manhattan, KS 66506, USA
    Autoimmun Rev 5:89-92. 2006
    ..Our experiments demonstrate that naturally occurring antibodies and autoantibodies mediate tissue injury only after an organ has been subjected to a stressor such as ischemia...
  11. ncbi request reprint Accelerated ischemia/reperfusion-induced injury in autoimmunity-prone mice
    Sherry D Fleming
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
    J Immunol 173:4230-5. 2004
    ....
  12. ncbi request reprint Increased caspase-3 expression and activity contribute to reduced CD3zeta expression in systemic lupus erythematosus T cells
    Sandeep Krishnan
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910 7500, USA
    J Immunol 175:3417-23. 2005
    ..We conclude that caspase-3 inhibitors can normalize SLE T cell function by limiting the excessive digestion of CD3zeta-chain and suggest that such molecules can be considered in the treatment of this disease...
  13. ncbi request reprint Systems biology in systemic lupus erythematosus: integrating genes, biology and immune function
    Vasileios C Kyttaris
    Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
    Autoimmunity 39:705-9. 2006
    ..Despite recent breakthroughs though, it is still unclear how exactly genes and environment interact to produce the characteristic immune dysregulation in SLE...
  14. ncbi request reprint Phosphorylated ERM is responsible for increased T cell polarization, adhesion, and migration in patients with systemic lupus erythematosus
    Yansong Li
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
    J Immunol 178:1938-47. 2007
    ..These data prove that increased ERM phosphorylation represents a key molecular abnormality that guides T cell adhesion and migration in SLE patients...
  15. ncbi request reprint T cell abnormalities in human and mouse lupus: intrinsic and extrinsic
    George C Tsokos
    Department of Medicine, Uniformed Services University, Bethesda, Maryland, USA
    Curr Opin Rheumatol 15:542-7. 2003
    ..The works reviewed imply that self-peptides might be considered to reestablish lost tolerance, whereas correction of the aberrant biochemistry might normalize T cell function and limit disease...
  16. ncbi request reprint TCR zeta-chain abnormalities in human systemic lupus erythematosus
    Madhusoodana P Nambiar
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD, USA
    Methods Mol Med 102:49-72. 2004
    ..The optimized methods and protocols described here pertaining to TCR zeta-chain expression and related T-cell signaling abnormalities can be very well applied to other molecules aberrantly expressed in SLE T cells...
  17. ncbi request reprint Abnormal B cell signal transduction in systemic lupus erythematosus
    Islam U Khan
    Section on Rheumatology and Clinical Immunology, Department of Internal Medicine, Wake Forest University School of Medicine, Winston Salem, N C, USA
    Curr Dir Autoimmun 6:89-104. 2003
  18. ncbi request reprint Direct transfer of p65 into T lymphocytes from systemic lupus erythematosus patients leads to increased levels of interleukin-2 promoter activity
    Thomas M Herndon
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA
    Clin Immunol 103:145-53. 2002
    ....
  19. ncbi request reprint Reconstitution of deficient T cell receptor zeta chain restores T cell signaling and augments T cell receptor/CD3-induced interleukin-2 production in patients with systemic lupus erythematosus
    Madhusoodana P Nambiar
    Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA
    Arthritis Rheum 48:1948-55. 2003
    ..This study was undertaken to explore the possibility that forced expression of TCR zeta chain may reverse the known signaling abnormalities and defective interleukin-2 (IL-2) production in SLE T cells...
  20. ncbi request reprint Abnormal expression of various molecular forms and distribution of T cell receptor zeta chain in patients with systemic lupus erythematosus
    Madhusoodana P Nambiar
    Walter Reed Army Institute of Research, Silver Spring, Maryland, 20910 7500, USA
    Arthritis Rheum 46:163-74. 2002
    ..This study was undertaken to investigate the complete spectrum of expression of the different forms and distribution of the TCR zeta chain in SLE T cells...
  21. ncbi request reprint Abnormal T lymphocyte signal transduction in systemic lupus erythematosus
    Gary M Kammer
    Section on Rheumatology and Clinical Immunology, Department of Internal Medicine, Wake Forest University School of Medicine, Winston Salem, N C, USA
    Curr Dir Autoimmun 5:131-50. 2002
  22. pmc Cholera toxin B accelerates disease progression in lupus-prone mice by promoting lipid raft aggregation
    Guo Min Deng
    Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 181:4019-26. 2008
    ..Our results demonstrate that lipid rafts contribute significantly to the pathogenesis of lupus and provide a novel mechanism whereby aggregated lipid rafts represent a potential link between infection and autoimmunity...
  23. ncbi request reprint Forced expression of the Fc receptor gamma-chain renders human T cells hyperresponsive to TCR/CD3 stimulation
    Madhusoodana P Nambiar
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
    J Immunol 170:2871-6. 2003
    ..We propose that altered composition of the CD3 complex leads to increased T cell responsiveness to TCR/CD3 stimulation and sets the biochemical grounds for the development of autoimmunity...
  24. ncbi request reprint The FcR gamma subunit and Syk kinase replace the CD3 zeta-chain and ZAP-70 kinase in the TCR signaling complex of human effector CD4 T cells
    Sandeep Krishnan
    Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    J Immunol 170:4189-95. 2003
    ..This physiologic switch in TCR signaling occurs exclusively in effector, and not naive or memory T cells, suggesting a potential target for manipulation of effector responses in autoimmune, malignant, and infectious diseases...
  25. pmc PP2A dephosphorylates Elf-1 and determines the expression of CD3zeta and FcRgamma in human systemic lupus erythematosus T cells
    Yuang Taung Juang
    Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 181:3658-64. 2008
    ..Therefore, PP2A serves as a central determinant of abnormal T cell function in human lupus and may represent an appropriate treatment target...
  26. ncbi request reprint Autoimmune odyssey on the Aegean Sea
    Mark J Mamula
    Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06520 8031, USA
    Nat Immunol 7:219-21. 2006
  27. ncbi request reprint T lymphocytes in systemic lupus erythematosus: an update
    Vasileios C Kyttaris
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
    Curr Opin Rheumatol 16:548-52. 2004
    ..The purpose of this review is to discuss recent studies that shed light into the pathogenetic mechanisms underlying T-cell dysfunction in systemic lupus erythematosus...
  28. ncbi request reprint FcRgamma chain does not replace CD3zeta chain in CD3zeta-deficient T lymphocytes of patients with gastric adenocarcinoma
    Mercedes Lopez-Santalla
    Inmunologia, Facultad de Medicina, Universidad Complutense de Madrid, Pabellon 5, 4 a planta, 28040 Madrid, Spain
    Mol Immunol 44:2400-5. 2007
    ..This altered expression of signalling molecules in T lymphocytes of cancer patients, would explain their low proliferative capacity. Our T-cell lines represent tools to unveil the signalling abnormalities of cancer T lymphocytes...
  29. ncbi request reprint Stability and translation of TCR zeta mRNA are regulated by the adenosine-uridine-rich elements in splice-deleted 3' untranslated region of zeta-chain
    Bhabadeb Chowdhury
    Department of Cellular Injury, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
    J Immunol 177:8248-57. 2006
    ..The absence of these sequences represents a molecular mechanism that contributes to altered TCR zeta-chain expression in lupus...
  30. ncbi request reprint Transcriptional repression of interleukin-2 in human systemic lupus erythematosus
    Christina G Katsiari
    Dept of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20190, USA
    Autoimmun Rev 5:118-21. 2006
    ..T cells from patients with SLE produce decreased amounts of interleukin-2 (IL-2), a central cytokine in the regulation of the immune response. We discuss herein the abnormalities underlying IL-2 deficiency in SLE T cells...
  31. ncbi request reprint Autoimmunity in systemic lupus erythematosus: integrating genes and biology
    Sandeep Krishnan
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
    Semin Immunol 18:230-43. 2006
    ..This review highlights recent discoveries of important functional genetic variants and altered expression of normal signaling proteins that network together to disrupt peripheral tolerance and initiate the autoimmune process in SLE...
  32. ncbi request reprint Increased levels of NF-ATc2 differentially regulate CD154 and IL-2 genes in T cells from patients with systemic lupus erythematosus
    Vasileios C Kyttaris
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
    J Immunol 178:1960-6. 2007
    ..The absence of important transcriptional activators (AP-1, NF-kappaBeta) and the presence of transcriptional repressors (cAMP response element modulator) on the IL-2 promoter explain this dichotomous effect...
  33. ncbi request reprint Pathology and immunology of lupus glomerulonephritis: can we bridge the two?
    Helen Liapis
    Department of Pathology and Immunology, Division of Anatomic and Molecular Pathology, Washington University School of Medicine, 660 South Euclid Avenue Campus, 8118, St Louis, MO 63110, USA
    Int Urol Nephrol 39:223-31. 2007
    ..This review summarizes current concepts in lupus immune pathogenesis and attempts to bridge immunology to pathology of lupus glomerulonephritis...
  34. doi request reprint Calcium signaling in systemic lupus erythematosus lymphocytes and its therapeutic exploitation
    George C Tsokos
    Arthritis Rheum 58:1216-9. 2008
  35. ncbi request reprint Increased expression of STAT3 in SLE T cells contributes to enhanced chemokine-mediated cell migration
    Tatsuhiro Harada
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD, USA
    Autoimmunity 40:1-8. 2007
    ..Our data suggest that inhibition of STAT3 expression may reverse the signaling aberrations involved in SLE T cell migration...
  36. pmc T cells and in situ cryoglobulin deposition in the pathogenesis of lupus nephritis
    Robert A Cohen
    Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    Clin Immunol 128:1-7. 2008
    ..The contribution of cryoglobulins and T cells in the expression of kidney pathology is discussed...
  37. ncbi request reprint Anti-ribonucleoprotein antibodies mediate enhanced lung injury following mesenteric ischemia/reperfusion in Rag-1(-/-) mice
    Michael P Keith
    Department of Rheumatology, National Naval Medical Center, Bethesda, MD, USA
    Autoimmunity 40:208-16. 2007
    ..These experiments reveal a novel mechanism whereby anti-RNP Abs contributes to the development of pulmonary pathology in patients with autoimmune diseases following exposure of remote organs to I/R injury...
  38. pmc Systemic lupus erythematosus: new molecular targets
    Jose C Crispin
    Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, 4 Blackfan Circle, HIM 244, Boston, MA 02115, USA
    Ann Rheum Dis 66:iii65-9. 2007
    ..The aim of this article is to review the findings that have allowed us to better understand the behaviour of the lupus T cell and highlight the molecules that represent potential therapeutic targets...
  39. pmc Novel molecular targets in the treatment of systemic lupus erythematosus
    Jose C Crispin
    Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, 4 Blackfan Circle, HIM 244, Boston, MA 02115, USA
    Autoimmun Rev 7:256-61. 2008
    ..The aim of this communication is to review the defects that have been consistently documented in SLE T cells, highlighting molecules and pathways that represent therapeutic targets...
  40. doi request reprint Common variable immune deficiency (CVID) presenting as an autoimmune disease: role of memory B cells
    Bret R Haymore
    Department of Allergy and Immunology, Walter Reed Army Medical Center, Washington, DC, USA
    Autoimmun Rev 7:309-12. 2008
    ..Review of the literature suggests that splenectomy should be avoided in patients with immune cytopenia and CVID and that serum immunoglobulins should be obtained in patients presenting with immune cytopenias to screen for CVID...
  41. ncbi request reprint In the beginning was Sm
    George C Tsokos
    J Immunol 176:1295-6. 2006
  42. ncbi request reprint New insights into the pathogenesis of systemic lupus erythematosus
    Vasileios C Kyttaris
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
    Curr Rheumatol Rep 7:469-75. 2005
    ..This leads to the production of an array of inflammatory cytokines, diverse autoantibodies, and immune complexes that in turn activate effector cells and the complement system leading to the clinical manifestations of the disease...
  43. pmc The TRAIL to arthritis
    George C Tsokos
    Walter Reed Army Institute of Research, Building 503, Room 1A32, Robert Grand Road, Silver Spring, Maryland 20910, USA
    J Clin Invest 112:1315-7. 2003
    ..These results suggest that gene-modified cell therapy represents a therapeutic option for systemic rheumatic diseases...
  44. ncbi request reprint C5a causes limited, polymorphonuclear cell-independent, mesenteric ischemia/reperfusion-induced injury
    Sherry D Fleming
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910 7500, USA
    Clin Immunol 108:263-73. 2003
    ..We conclude that although C5a can trigger certain components of the IR induced injury, other mediators such as C5b-9 and local factors are needed for the complete expression of IR tissue damage...
  45. ncbi request reprint Antisense cyclic adenosine 5'-monophosphate response element modulator up-regulates IL-2 in T cells from patients with systemic lupus erythematosus
    Klaus Tenbrock
    Department of Cellular Injury, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
    J Immunol 169:4147-52. 2002
    ..Our data demonstrate that antisense constructs can be used to effectively eliminate the expression of a transcriptional repressor. This approach can be used therapeutically in conditions where increased production of IL-2 is desired...
  46. ncbi request reprint Rewiring the T-cell: signaling defects and novel prospects for the treatment of SLE
    George C Tsokos
    Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
    Trends Immunol 24:259-63. 2003
  47. ncbi request reprint Activation of the Ets transcription factor Elf-1 requires phosphorylation and glycosylation: defective expression of activated Elf-1 is involved in the decreased TCR zeta chain gene expression in patients with systemic lupus erythematosus
    George C Tsokos
    Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA
    Ann N Y Acad Sci 987:240-5. 2003
    ..Therefore, a novel activation pathway for a member of the Ets family of transcription factors, which is defective in patients with systemic autoimmunity, has been revealed...
  48. ncbi request reprint Transcriptional activation of the human inducible nitric-oxide synthase promoter by Kruppel-like factor 6
    Vishal G Warke
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA
    J Biol Chem 278:14812-9. 2003
    ..These findings indicate that KLF6 is a potential transactivator of the human iNOS promoter in diverse pathophysiological conditions...
  49. ncbi request reprint C5 is required for CD49d expression on neutrophils and VCAM expression on vascular endothelial cells following mesenteric ischemia/reperfusion
    Sherry D Fleming
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
    Clin Immunol 106:55-64. 2003
    ....
  50. ncbi request reprint Lupus: immunity gone awry
    George C Tsokos
    Health News 8:1-2. 2002
  51. ncbi request reprint Mice deficient in complement receptors 1 and 2 lack a tissue injury-inducing subset of the natural antibody repertoire
    Sherry D Fleming
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
    J Immunol 169:2126-33. 2002
    ..In sum, CR2/CR1 play an unanticipated but critical role in the development of a subset of the natural Ab repertoire that has particular importance in the pathogenesis of IR injury...
  52. ncbi request reprint Abnormal T cell signal transduction in systemic lupus erythematosus
    Gary M Kammer
    Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    Arthritis Rheum 46:1139-54. 2002
  53. ncbi request reprint Effect of trichostatin A on human T cells resembles signaling abnormalities in T cells of patients with systemic lupus erythematosus: a new mechanism for TCR zeta chain deficiency and abnormal signaling
    Madhusoodana P Nambiar
    Department of Cellular Injury, Walter Reed Army Institute of Research, Building 503, Robert Grant Road, Silver Spring, Maryland 20910 7500, USA
    J Cell Biochem 85:459-69. 2002
    ..The effects of TSA on human T cells are predominantly immunosuppressive and reminiscent of the signaling aberrations that have been described in patients with systemic lupus erythematosus...
  54. ncbi request reprint Dissecting the molecular mechanisms of TCR zeta chain downregulation and T cell signaling abnormalities in human systemic lupus erythematosus
    Madhusoodana P Nambiar
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, and Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
    Int Rev Immunol 23:245-63. 2004
    ....
  55. ncbi request reprint Transcriptional regulation of interleukin 2 in SLE T cells
    Klaus Tenbrock
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
    Int Rev Immunol 23:333-45. 2004
    ..This article will review the defective transcription regulation of IL-2 in SLE T cells, which is the result of decreased expression of the enhancers NF-kappa B and AP1 and the increased expression of the transcriptional repressor CREM...
  56. ncbi request reprint T-cell signaling abnormalities in human systemic lupus erythematosus
    Madhusoodana P Nambiar
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD, USA
    Methods Mol Med 102:31-47. 2004
    ....
  57. ncbi request reprint The cyclic AMP response element modulator regulates transcription of the TCR zeta-chain
    Klaus Tenbrock
    Department of Pediatrics, Division of Rheumatology, University Hospital, Muenster, Germany
    J Immunol 175:5975-80. 2005
    ..Our studies demonstrate that CREM alpha binds to the TCR zeta promoter and repress its activity...
  58. pmc Protein phosphatase 2A is a negative regulator of IL-2 production in patients with systemic lupus erythematosus
    Christina G Katsiari
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA
    J Clin Invest 115:3193-204. 2005
    ..We propose the use of PP2Ac-siRNA as a novel tool to correct T cell IL-2 production in SLE patients...
  59. ncbi request reprint Monoclonal antibodies and fusion proteins in medicine
    Stamatis Nick C Liossis
    Division of Rheumatology, Department of Internal Medicine, University of Patras Medical School, Patras, Greece
    J Allergy Clin Immunol 116:721-9; quiz 730. 2005
    ..Further insights are needed regarding limitation of adverse effects, correct use in conjunction with existing drugs, and treatment of patients in whom resistance develops...
  60. ncbi request reprint Rituximab anti-B-cell therapy in systemic lupus erythematosus: pointing to the future
    Petros P Sfikakis
    First Department of Propedeutic and Internal Medicine, Athens University Medical School, Greece
    Curr Opin Rheumatol 17:550-7. 2005
    ..To discuss the clinical effects and the immunologic consequences of transient B-cell depletion using the anti-CD20 monoclonal antibody rituximab in systemic lupus erythematosus...
  61. ncbi request reprint Immune cells and cytokines in systemic lupus erythematosus: an update
    Vasileios C Kyttaris
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
    Curr Opin Rheumatol 17:518-22. 2005
    ..This article reviews recent studies unraveling the complex interplay between cytokines and lymphocytes in systemic lupus erythematosus...
  62. ncbi request reprint Systemic lupus erythematosus and Sjögren's syndrome
    George C Tsokos
    Curr Opin Rheumatol 17:511-2. 2005
  63. ncbi request reprint T cell-to-T cell clustering enhances NF-kappaB activity by a PI3K signal mediated by Cbl-b and Rho
    Thomas M Herndon
    Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
    Biochem Biophys Res Commun 332:1133-9. 2005
    ..Taken together, these results suggest that in addition to pathways stimulated by classical T cell-APC interactions, another signal arising from T cell clustering can enhance activation...
  64. pmc Systemic lupus erythematosus serum IgG increases CREM binding to the IL-2 promoter and suppresses IL-2 production through CaMKIV
    Yuang Taung Juang
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA
    J Clin Invest 115:996-1005. 2005
    ....
  65. ncbi request reprint Decreased stability and translation of T cell receptor zeta mRNA with an alternatively spliced 3'-untranslated region contribute to zeta chain down-regulation in patients with systemic lupus erythematosus
    Bhabadeb Chowdhury
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910 7500, USA
    J Biol Chem 280:18959-66. 2005
    ..Taken together our findings suggest that nucleotides 672-1233 bp of TCR zeta 3' UTR play a critical role in its stability and also have elements required for the translational regulation of TCR zeta chain expression in human T cells...
  66. ncbi request reprint Exploring complement activation to develop biomarkers for systemic lupus erythematosus
    George C Tsokos
    Arthritis Rheum 50:3404-7. 2004
  67. ncbi request reprint Cyclic adenosine 5'-monophosphate response element modulator is responsible for the decreased expression of c-fos and activator protein-1 binding in T cells from patients with systemic lupus erythematosus
    Vasileios C Kyttaris
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
    J Immunol 173:3557-63. 2004
    ..We conclude that CREM represses the expression of c-fos and limits the activity of the enhancer AP-1. Thus, CREM is involved indirectly in the modulation of transcriptional regulation of multiple genes including IL-2...
  68. ncbi request reprint Emerging concepts in the molecular pathogenesis of systemic lupus erythematosus
    Madhusoodana P Nambiar
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910 7500, USA
    Arch Immunol Ther Exp (Warsz) 50:35-45. 2002
    ..Understanding the immune cell signaling and gene transcription abnormalities will help us tailor new strategies for efficient biotherapy of the disease...

Research Grants38

  1. CIS School on Systemic Autoimmune Diseases
    George Tsokos; Fiscal Year: 2006
    ..The School will be residential in character and held in an informal setting and will attract applicants from North America, Europe and Asia. There will be 10 faculty and 25 fellows selected to attend. ..
  2. LYMPHOCYTE SIGNALING DEFECTS IN PATIENTS WITH LUPUS
    George Tsokos; Fiscal Year: 2007
    ..Abnormal steps can be reversed with drugs and have the potential to complement existing therapeutic modalities. ..
  3. Phosphatases in Human Lupus
    George Tsokos; Fiscal Year: 2007
    ..In addition, the produced information will introduce new approaches to correct the abnormal expression of PP2Ac and reverse the decreased IL-2 production and defective T cell function. ..
  4. CIS School on Systemic Autoimmune Diseases
    George Tsokos; Fiscal Year: 2007
    ..The school will be residential in character and held in an informal setting and will attract applicants from the North America, Europe and Asia. Ten faculty and 25 fellows will be selected to attend. ..
  5. Gene Transcription in SLE
    George Tsokos; Fiscal Year: 2006
    ..Defective IL-2 production contributes to increased infection-related morbidity and mortality rates in patients with SLE. The proposed studies will contribute to our understanding of the origin of a major clinical problem. ..
  6. Gene Transcription in SLE
    George Tsokos; Fiscal Year: 2009
    ..The proposed studies will explore the mechanisms that lead to decreased production of interleukin-2 in order to identify molecules that we can target for therapeutic purposes. ..
  7. LYMPHOCYTE SIGNALING DEFECTS IN PATIENTS WITH LUPUS
    George Tsokos; Fiscal Year: 2009
    ..This application will explore the presence of molecular targets that can be modulated with gene transfer or drugs and have the potential to complement existing therapeutic modalities. ..
  8. Gene Transcription in SLE
    George C Tsokos; Fiscal Year: 2010
    ..The proposed studies will explore the mechanisms that lead to decreased production of interleukin-2 in order to identify molecules that we can target for therapeutic purposes. ..
  9. Phosphatases in Human Lupus
    George C Tsokos; Fiscal Year: 2010
    ..In addition, the produced information will introduce new approaches to correct the abnormal expression of PP2Ac and reverse the decreased IL-2 production and defective T cell function. ..
  10. Expanded double negative T cells in SLE
    George C Tsokos; Fiscal Year: 2010
    ..Current treatment is based primarily on indiscriminate immunosuppression. This proposal will identify IL-17 as a novel treatment target and will generate information to introduce Th17 cells as a biomarker of disease activity. ..
  11. LYMPHOCYTE SIGNALING DEFECTS IN PATIENTS WITH LUPUS
    George Tsokos; Fiscal Year: 2006
    ..Abnormal steps can be reversed with drugs and have the potential to complement existing therapeutic modalities. ..
  12. REGULATION OF COMPLEMENT RECEPTOR GENE EXPRESSION
    George Tsokos; Fiscal Year: 2002
    ..Since we have found that sera from patients with systemic autoimmune diseases have antibodies directed against this hnRNP, we propose to study their frequency and clinical significance. ..
  13. LYMPHOCYTE SIGNALING DEFECTS IN PATIENTS WITH LUPUS
    George Tsokos; Fiscal Year: 2002
    ..Experiments will be performed to consider the alternative hypothesis, i.e., zetu chain deficiency in lupus cells is the result of cell activation or other cellular regulatory abnormality. ..
  14. Systemic Autoimmune Diseases; 2003 Summer School
    George Tsokos; Fiscal Year: 2003
    ..There will be 8 faculty and 25 fellows. Only fellows from the United States will receive funding made possible through the NIH grant. ..
  15. T cell help in the B cell response to malaria CS protein
    George Tsokos; Fiscal Year: 2004
    ..abstract_text> ..
  16. LYMPHOCYTE SIGNALING DEFECTS IN PATIENTS WITH LUPUS
    George C Tsokos; Fiscal Year: 2010
    ..This application will explore the presence of molecular targets that can be modulated with gene transfer or drugs and have the potential to complement existing therapeutic modalities. ..