Igor Dozmorov

University of Texas Southwestern Medical Center, Dallas, Texas, United States

Are you Igor Dozmorov?

Claim your profile

Publications (105)303.86 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Recognition of pathogen-associated molecular patterns by Toll-like receptors (TLRs) on dendritic cells (DCs) leads to DC maturation, a process involving up-regulation of MHC and costimulatory molecules and secretion of proinflammatory cytokines. All TLRs except TLR3 achieve these outcomes by using the signaling adaptor myeloid differentiation factor 88. TLR4 and TLR3 can both use the Toll-IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF)-dependent signaling pathway leading to IFN regulatory factor 3 (IRF3) activation and induction of IFN-β and -α4. The TRIF signaling pathway, downstream of both of these TLRs, also leads to DC maturation, and it has been proposed that the type I IFNs act in cis to induce DC maturation and subsequent effects on adaptive immunity. The present study was designed to understand the molecular mechanisms of TRIF-mediated DC maturation. We have discovered that TLR4-TRIF-induced DC maturation was independent of both IRF3 and type I IFNs. In contrast, TLR3-mediated DC maturation was completely dependent on type I IFN feedback. We found that differential activation of mitogen-activated protein kinases by the TLR4- and TLR3-TRIF axes determined the type I IFN dependency for DC maturation. In addition, we found that the adjuvanticity of LPS to induce T-cell activation is completely independent of type I IFNs. The important distinction between the TRIF-mediated signaling pathways of TLR4 and TLR3 discovered here could have a major impact in the design of future adjuvants that target this pathway.
    No preview · Article · Oct 2015 · Proceedings of the National Academy of Sciences
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite major advances in our understanding of TGF-β signaling in multiple cell types, little is known about the direct target genes of this pathway in human eosinophils. These cells constitute the major inflammatory component present in the sputum and lung of active asthmatics and their numbers correlate well with disease severity. During the transition from acute to chronic asthma, TGF-β levels rise several fold in the lung which drives fibroblasts to produce extracellular matrix (ECM) and participate in airway and parenchymal remodeling. In this report, we use purified blood eosinophils from healthy donors and analyze baseline and TGF-β responsive genes by RNA Seq, and demonstrate that eosinophils (PBE) express 7,981 protein-coding genes of which 178 genes are up-regulated and 199 genes are down-regulated by TGF-β. While 18 target genes have been previously associated with asthma and eosinophilic disorders, the vast majority have been implicated in cell death and survival, differentiation, and cellular function. Ingenuity pathway analysis revealed that 126 canonical pathways are activated by TGF-β including iNOS, TREM1, p53, IL-8 and IL-10 signaling. As TGF-β is an important cytokine for eosinophil function and survival, and pulmonary inflammation and fibrosis, our results represent a significant step toward the identification of novel TGF-β responsive genes and provide a potential therapeutic opportunity by selectively targeting relevant genes and pathways. Copyright © 2015. Published by Elsevier B.V.
    No preview · Article · Jun 2015 · Immunology letters
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Approximately 40% of patients who survive acute episodes of thrombotic thrombocytopenic purpura (TTP) associated with severe acquired ADAMTS13 deficiency experience one or more relapses. Risk factors for relapse other than severe ADAMTS13 deficiency and ADAMTS13 autoantibodies are unknown. ADAMTS13 autoantibodies, TTP episodes following infection or type I interferon treatment and reported ensuing systemic lupus erythematosus in some patients suggest immune dysregulation. This cross-sectional study asked whether autoantibodies against RNA-binding proteins or peripheral blood gene expression profiles measured during remission are associated with history of prior relapse in acquired ADAMTS13-deficient TTP. Peripheral blood from 38 well-characterized patients with autoimmune ADAMTS13-deficient TTP in remission was examined for autoantibodies and global gene expression. A subset of TTP patients (9 patients, 24%) exhibited a peripheral blood gene signature composed of elevated ribosomal transcripts that associated with prior relapse. A non-overlapping subset of TTP patients (9 patients, 24%) displayed a peripheral blood type I interferon gene signature that associated with autoantibodies to RNA-binding proteins but not with history of relapse. Patients who had relapsed bimodally expressed higher HLA transcript levels independently of ribosomal transcripts. Presence of any one potential risk factor (ribosomal gene signature, elevated HLA-DRB1, elevated HLA-DRB5) associated with relapse (OR = 38.4; p = 0.0002) more closely than any factor alone or all factors together. Levels of immune transcripts typical of natural killer (NK) and T lymphocytes positively correlated with ribosomal gene expression and number of prior episodes but not with time since the most recent episode. Flow cytometry confirmed elevated expression of cell surface markers encoded by these transcripts on T and/or NK cell subsets of patients who had relapsed. These data associate elevated ribosomal and immune transcripts with relapse history in acquired, ADAMTS13-deficient TTP.
    Full-text · Article · Feb 2015 · PLoS ONE
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Changes in immune function during the course of systemic lupus erythematosus (SLE) are well characterized. Class-switched antinuclear antibodies are the hallmark of SLE, and T/B- cell interactions are thus critical. However, changes in immune function contributing to disease susceptibility are unknown. Here, we have analyzed primary T and B cells from a mouse model of SLE prior to the onset of disease. To allow cognate T-cell activation with low affinity, we have developed a lower potency peptide ligand for the OTII T-cell receptor. T and B-cell couples formed less frequently and retained their polarity less efficiently preferentially in response to low affinity stimulation in SLE-prone mice. This matched decreased recruitment of actin and Vav1 and an enhanced PKCΘ recruitment to the cellular interface in T cells. The induction of the germinal center B-cell marker GL7 was increased in T/B cell couples from SLE-prone mice when the T-cell numbers were limited. However, the overall gene expression changes were marginal. Taken together, the enhanced cell couple transience may allow a more efficient sampling of a large number of T/B cell couples, preferentially in response to limiting stimuli, therefore enhancing the immune reactivity in the development of SLE.This article is protected by copyright. All rights reserved
    Full-text · Article · Dec 2014 · European Journal of Immunology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The breakdown in tolerance of autoreactive B cells in the lupus-prone NZM2410-derived B6.Sle1.Sle2.Sle3 (TC) mice results in the secretion of autoantibodies. TC dendritic cells (DCs) enhance B cell proliferation and antibody secretion in a cytokine-dependent manner. However, the specific cytokine milieu by which TC DCs activate B cells was not known. In this study, we compared TC and C57BL/6 (B6) control for the distribution of DC subsets and for their production of cytokines affecting B cell responses. We show that TC DCs enhanced B cell proliferation through the production of IL-6 and IFN-γ, while antibody secretion was only dependent on IL-6. Pre-disease TC mice showed an expanded PDCA1+ cells prior to disease onset that was localized to the marginal zone and further expanded with age. The presence of PDCA1+ cells in the marginal zone correlated with a Type I Interferon (IFN) signature in marginal zone B cells, and this response was higher in TC than B6 mice. In vivo administration of anti-chromatin immune complexes upregulated IL-6 and IFN-γ production by splenic DCs from TC but not B6 mice. The production of BAFF and APRIL was decreased upon TC DC stimulation both in vitro and in vivo, indicating that these B cell survival factors do not play a role in B cell modulation by TC DCs. Finally, TC B cells were defective at downregulating IL-6 expression in response to anti-inflammatory apoptotic cell exposure. Overall, these results show that the TC autoimmune genetic background induces the production of B cell-modulating inflammatory cytokines by DCs, which are regulated by the microenvironment as well as the interplay between DC.
    Full-text · Article · Aug 2014 · PLoS ONE
  • Ruth Levitz · Igor Dozmorov · Ran Song · Edward K. Wakeland
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: The mechanisms of pathogenesis of respiratory syncytial virus (RSV) remain poorly defined. It is not clear why certain infants are prone to severe RSV infection. We sought to determine whether there was variation in the innate immune response to RSV among individuals. Likewise, we sought to determine whether clinical isolates of RSV differ in their capacity to activate gene expression during infection of primary human macrophages. Methods: Clinical isolates of RSV were used to infect primary human macrophages from a variety of donors. Concentrations of secreted cytokines were determined by Bio-Plex assay. The transcriptome of infected cells were determined utilizing RNA-SEQ technology. Heatmaps of gene expression dynamics in infected cells were generated with the Spotfire Decision Site 9 software. Gene subsets were created from the list of genes involved in response to viral infection. Functional analysis of identified genes was performed with Ingenuity Pathway Analysis. Results: RSV activated genes involved in multiple processes including response to virus entry, virus replication, virus recognition, activation of the innate immune system and response to interferon. Overall, at least 2 distinct patterns were observed among donors suggesting that the innate response to viral infection differs among individuals. Furthermore, we observed distinct patterns of activation of genes among different clinical isolates of RSV. These data suggest that there is significant variability of clinical isolates of RSV to activate or inhibit the innate immune system. Signaling pathway analyses revealed that the magnitude of pathway activation, rather than the specific pathways activated accounted for the differences in gene expression among the viruses studied. Conclusion: These data suggest that the innate immune response to RSV may determine the severity of disease. Our data also indicates that RSV strains are not homogeneous with regard to activation or inhibition of the innate immune response in primary human macrophages. Identification of the viral genetic polymorphisms associated with activation or inhibition of the innate immune response may lead to the development of effective antiviral agents and vaccines.
    No preview · Conference Paper · Oct 2013
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent application of gene expression profiling to the immune system has shown a great potential for characterization of complex regulatory processes. It is becoming increasingly important to characterize functional systems through multigene interactions to provide valuable insights into differences between healthy controls and autoimmune patients. Here we apply an original systematic approach to the analysis of changes in regulatory gene interconnections between in Epstein-Barr virus transformed hyperresponsive B cells from SLE patients and normal control B cells. Both traditional analysis of differential gene expression and analysis of the dynamics of gene expression variations were performed in combination to establish model networks of functional gene expression. This Pathway Dysregulation Analysis identified known transcription factors and transcriptional regulators activated uniquely in stimulated B cells from SLE patients.
    Full-text · Article · Aug 2013 · PLoS ONE
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Patients with 22q11.2 deletion syndrome have heterogeneous clinical presentations including immunodeficiency, cardiac anomalies, and hypocalcemia. The syndrome arises from hemizygous deletions of up to 3Mb on chromosome 22q11.2, a region that contains 60 genes and 4 microRNAs. MicroRNAs are important post-transcriptional regulators of gene expression, with mutations in several microRNAs causal to specific human diseases. We characterized the microRNA expression patterns in the peripheral blood of patients with 22q11.2 deletion syndrome (n=31) compared to normal controls (n=22). Eighteen microRNAs had a statistically significant differential expression (p<0.05), with miR-185 expressed at 0.4× normal levels. The 22q11.2 deletion syndrome cohort exhibited microRNA expression hyper-variability and group dysregulation. Selected microRNAs distinguished patients with cardiac anomalies, hypocalcemia, and/or low circulating T cell counts. In summary, microRNA profiling of chromosome 22q11.2 deletion syndrome/DiGeorge patients revealed a signature microRNA expression pattern distinct from normal controls with clinical relevance.
    Full-text · Article · Jan 2013 · Clinical Immunology
  • Source

    Full-text · Dataset · Dec 2012
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The sensing of viral nucleic acids by the innate immune system triggers the production of type I interferons, which activates interferon-stimulated genes (ISGs) and directs a multifaceted antiviral response. ISGs can also be activated through interferon-independent pathways, although the precise mechanisms remain elusive. Here we found that the cytosolic exonuclease Trex1 regulated the activation of a subset of ISGs independently of interferon. Both Trex1(-/-) mouse cells and Trex1-mutant human cells had high expression of genes encoding antiviral molecules ('antiviral genes') and were refractory to viral infection. The interferon-independent activation of antiviral genes in Trex1(-/-) cells required the adaptor STING, the kinase TBK1 and the transcription factors IRF3 and IRF7. We also found that Trex1-deficient cells had an expanded lysosomal compartment, altered subcellular localization of the transcription factor TFEB and diminished activity of the regulator mTORC1. Together our data identify Trex1 as a regulator of lysosomal biogenesis and interferon-independent activation of antiviral genes and show that dysregulation of lysosomes can elicit innate immune responses.
    Full-text · Article · Nov 2012 · Nature Immunology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Respiratory syncytial virus (RSV) is the major respiratory pathogen of infants and young children. Like other RNA viruses, RSV genome replication is prone to errors that results in a heterogeneous population of viral strains some of which may possess differences in pathogenesis and virulence. We sought to determine whether clinical isolates of RSV differ in their capacity to induce inflammatory cytokines and gene expression during infection of human pulmonary epithelial cells and primary human macrophages. Methods: Plaque purified clinical isolates of RSV were used to infect human pulmonary epithelial A549 cells and primary human macrophages from a variety of donors. Concentrations of secreted cytokines were determined by Bio-Plex assay. The transcriptome of infected cells were determined utilizing RNA-SEQ technology. Results: Two RSV subgroup B isolates, NH1067 and NH1125, were identified that differed in their capacity to induce cytokines during infection of A549 cells. Specifically, the level of induction of both IL-6 and RANTES by NH1125 was statistically significantly greater compared to NH1067. The distinct cytokine induction phenotype of the viruses was recapitulated in primary human macrophages. Overall, the level of cytokine induction by NH1125 was greater than NH1067 for all donors tested. Several other subgroup B isolates were identified that had phenotypes that were similar to either NH1125 or NH1067. Transcriptome analyses of infected A549 cells infected with either NH1067 or NH1125 revealed differential RNA expression profiles further supporting the hypothesis that the 2 viruses are phenotypically distinct in their ability to stimulate the innate immune response in A549 cells. Signaling pathway analyses revealed that the magnitude of pathway activation, rather than the specific pathways activated accounted for the differences in gene expression between the 2 viruses. Conclusion: These data suggest that RSV strains are not homogeneous with regard to pathogenesis or virulence. Identification of the viral genetic polymorphisms associated with cytokine induction may lead to the development of effective antiviral agents and vaccines.
    No preview · Conference Paper · Oct 2012
  • [Show abstract] [Hide abstract]
    ABSTRACT: Sle1c is a sublocus of the NZM2410-derived Sle1 major lupus susceptibility locus. We have shown previously that Sle1c contributes to lupus pathogenesis by conferring increased CD4(+) T cell activation and increased susceptibility to chronic graft-versus-host disease (cGVHD), which mapped to the centromeric portion of the locus. In this study, we have refined the centromeric sublocus to a 675-kb interval, termed Sle1c2. Mice from recombinant congenic strains expressing Sle1c2 exhibited increased CD4(+) T cell intrinsic activation and cGVHD susceptibility, similar to mice with the parental Sle1c. In addition, B6.Sle1c2 mice displayed a robust expansion of IFN-γ-expressing T cells. NZB complementation studies showed that Sle1c2 expression exacerbated B cell activation, autoantibody production, and renal pathology, verifying that Sle1c2 contributes to lupus pathogenesis. The Sle1c2 interval contains two genes, only one of which, Esrrg, is expressed in T cells. B6.Sle1c2 CD4(+) T cells expressed less Esrrg than B6 CD4(+) T cells, and Esrrg expression was correlated negatively with CD4(+) T cell activation. Esrrg encodes an orphan nuclear receptor that regulates oxidative metabolism and mitochondrial functions. In accordance with reduced Esrrg expression, B6.Sle1c2 CD4(+) T cells present reduced mitochondrial mass and altered mitochondrial functions as well as altered metabolic pathway utilization when compared with B6 CD4(+) T cells. Taken together, we propose Esrrg as a novel lupus susceptibility gene regulating CD4(+) T cell function through their mitochondrial metabolism.
    No preview · Article · Jun 2012 · The Journal of Immunology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients with 22q11.2 deletion syndrome present with heterogeneous clinical phenotypes. The syndrome arises from hemizygous deletions on chromosome 22q11.2, which comprises 60 genes, one is a microRNA binding protein termed DiGeorge Syndrome Critical Region 8, and 4 microRNAs. To determine the impact of this deletion on microRNA expression, we profiled microRNAs in peripheral blood from 31 patients with 22q11.2 deletion and 22 controls. Out of 600 microRNAs analyzed, 13 were differentially expressed in patients, and both a unique hypervariable expression and an abnormal clustering of microRNAs was noted. Selected microRNA groups could distinguish patients who had low numbers of circulating T cells from both normal controls and patients with normal T-cell numbers. The clinical triad of hypocalcemia, congenital heart disease and low circulating T cells was associated with a unique profile of microRNAs. In summary, microRNA profiling of patients with DiGeorge are revealing unique microRNA expression patterns and suggesting gene targets that may become relevant to understanding the molecular basis for clinical phenotypes and T cell development.
    No preview · Conference Paper · May 2012
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Sle1a.1 is part of the Sle1 susceptibility locus, which has the strongest association with lupus nephritis in the NZM2410 mouse model. In this study, we show that Sle1a.1 results in the production of activated and autoreactive CD4(+) T cells. Additionally, Sle1a.1 expression reduces the peripheral regulatory T cell pool, as well as induces a defective response of CD4(+) T cells to the retinoic acid expansion of TGF-β-induced regulatory T cells. At the molecular level, Sle1a.1 corresponds to an increased expression of a novel splice isoform of Pbx1, Pbx1-d. Pbx1-d overexpression is sufficient to induce an activated/inflammatory phenotype in Jurkat T cells and to decrease their apoptotic response to retinoic acid. PBX1-d is expressed more frequently in the CD4(+) T cells from lupus patients than from healthy controls, and its presence correlates with an increased central memory T cell population. These findings indicate that Pbx1 is a novel lupus susceptibility gene that regulates T cell activation and tolerance.
    Full-text · Article · Dec 2011 · The Journal of Immunology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Small-cell lung cancer (SCLC) is a highly malignant carcinoma with poor long-term survival. Effective treatment remains highly demanded. In the present study, we demonstrated that External Qi of Yan Xin Qigong (YXQ-EQ) exerted potent cytotoxic effect towards SCLC cell line NCI-H82 via induction of apoptosis. Global gene expression profiling identified 39 genes whose expression was altered by YXQ-EQ in NCI-82 cells. Among them, semi-quantitative RT-PCR and real-time qPCR analyses confirmed that the gene expression levels of apoptotic proteins death-associated protein kinase 2 and cell death-inducing DFFA-like effector b were upregulated, whereas that of oncoproteins DEK and MYCL1, cell migration-promoting proteins CD24 and integrin-alpha 9, and glycolytic enzyme aldolase A were downregulated. These findings suggest that YXQ-EQ may exert anticancer effect through modulating gene expression in a way that facilitates cancer cell apoptosis while represses proliferation, metastasis, and glucose metabolism.
    Full-text · Article · Dec 2011 · Molecular and Cellular Biochemistry

  • No preview · Article · Oct 2011 · Clinical Lymphoma, Myeloma and Leukemia
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The failure of chemotherapeutic regimens to eradicate cancers often results from the outgrowth of minor subclones with more dangerous genomic abnormalities or with self-renewing capacity. To explore such intratumor complexities in B-cell chronic lymphocytic leukemia (CLL), we measured B-cell kinetics in vivo by quantifying deuterium ((2)H)-labeled cells as an indicator of a cell that had divided. Separating CLL clones on the basis of reciprocal densities of chemokine (C-X-C motif) receptor 4 (CXCR4) and cluster designation 5 (CD5) revealed that the CXCR4(dim)CD5(bright) (proliferative) fraction contained more (2)H-labeled DNA and hence divided cells than the CXCR4(bright)CD5(dim) (resting) fraction. This enrichment was confirmed by the relative expression of two cell cycle-associated molecules in the same fractions, Ki-67 and minichromosome maintenance protein 6 (MCM6). Comparisons of global gene expression between the CXCR4(dim)CD5(bright) and CXCR4(bright)CD5(dim) fractions indicated higher levels of pro-proliferation and antiapoptotic genes and genes involved in oxidative injury in the proliferative fraction. An extended immunophenotype was also defined, providing a wider range of surface molecules characteristic of each fraction. These intraclonal analyses suggest a model of CLL cell biology in which the leukemic clone contains a spectrum of cells from the proliferative fraction, enriched in recently divided robust cells that are lymphoid tissue emigrants, to the resting fraction enriched in older, less vital cells that need to immigrate to lymphoid tissue or die. The model also suggests several targets preferentially expressed in the two populations amenable for therapeutic attack. Finally, the study lays the groundwork for future analyses that might provide a more robust understanding of the development and clonal evolution of this currently incurable disease.
    Full-text · Article · Sep 2011 · Molecular Medicine
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Individual cytokines and groups of cytokines that might represent networks in chronic lymphocytic leukemia (CLL) were analyzed and their prognostic values determined. Serum levels of 23 cytokines were measured in 84 patients and 49 age-matched controls; 17 levels were significantly elevated in patients. Unsupervised hierarchical bicluster analysis identified 3 clusters (CLs) of highly correlated but differentially expressed cytokines: CL1 (CXCL9, CXCL10, CXCL11, CCL3, CCL4, CCL19, IL-5, IL-12, and IFNγ), CL2 (TNFα, IL-6, IL-8, and GM-CSF), and CL3 (IL-1β, IL-2, IL-4, IL-15, IL-17, and IFNα). Combination scores integrating expression of CL1/CL2 or CL1/CL3 strongly correlated (P < .005) with time-to-first-treatment and overall survival (OS), respectively. Patients with the worst course had high CL1 and low CL2 or CL3 levels. Multivariate analysis revealed that CL1/CL2 combination score and immunoglobulin heavy chain variable region mutation status were independent prognostic indicators for time-to-first-treatment, whereas CL1/CL3 combination score and immunoglobulin heavy chain variable region mutation status were independent markers for OS. Thus, we identified groups of cytokines differentially expressed in CLL that are independent prognostic indicators of aggressive disease and OS. These findings indicate the value of multicytokine analyses for prognosis and suggest therapeutic strategies in CLL aimed at reducing CL1 and increasing CL2/CL3 cytokines.
    Full-text · Article · Sep 2011 · Blood
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A major virulence factor of Bacillus anthracis is the anthrax Lethal Toxin (LeTx), a bipartite toxin composed of Protective Antigen and Lethal Factor. Systemic administration of LeTx to laboratory animals leads to death associated with vascular leakage and pulmonary edema. In this study, we investigated whether systemic exposure of mice to LeTx would induce gene expression changes associated with vascular/capillary leakage in lung tissue. We observed enhanced susceptibility of A/J mice to death by systemic LeTx administration compared to the C57BL/6 strain. LeTx-induced groups of both up- and down-regulated genes were observed in mouse lungs 6 h after systemic administration of wild type toxin compared to lungs of mice exposed to an inactive mutant form of the toxin. Lungs of the less susceptible C57BL/6 strain showed 80% fewer differentially expressed genes compared to lungs of the more sensitive A/J strain. Expression of genes known to regulate vascular permeability was modulated by LeTx in the lungs of the more susceptible A/J strain. Unexpectedly, the largest set of genes with altered expression was immune specific, characterized by the up-regulation of lymphoid genes and the down-regulation of myeloid genes. Transcripts encoding neutrophil chemoattractants, modulators of tumor regulation and angiogenesis were also differentially expressed in both mouse strains. These studies provide new directions for the investigation of vascular leakage and pulmonary edema induced by anthrax LeTx.
    Full-text · Article · Sep 2011 · Toxins
  • Source
    Igor M Dozmorov · D Dresser
    [Show abstract] [Hide abstract]
    ABSTRACT: As suggested by the well-known gestalt concept the immune system can be regarded as an integrated complex system, the functioning of which cannot be fully characterized by the behavior of its constituent elements. Similar approaches to the immune system in particular and sensory systems in general allows one to discern similarities and differences in the process of distinguishing informative patterns in an otherwise random background, thus initiating an appropriate and adequate response. This may lead to a new interpretation of difficulties in the comprehension of some immunological phenomena.
    Preview · Article · Sep 2011 · International journal of biomedical science: IJBS

Publication Stats

1k Citations
303.86 Total Impact Points


  • 2012-2015
    • University of Texas Southwestern Medical Center
      • • Department of Immunology
      • • Department of Internal Medicine
      Dallas, Texas, United States
  • 2003-2012
    • Oklahoma Medical Research Foundation
      • Arthritis and Clinical Immunology Program
      Oklahoma City, Oklahoma, United States
  • 2011
    • North Florida and South Georgia Veterans Health System
      Gainesville, Florida, United States
    • University of Florida
      • Department of Pathology, Immunology, and Laboratory Medicine
      Gainesville, FL, United States
  • 2007
    • Johns Hopkins University
      Baltimore, Maryland, United States
    • Oklahoma City University
      Oklahoma City, Oklahoma, United States
  • 2003-2005
    • University of Oklahoma Health Sciences Center
      • Department of Physiology
      Oklahoma City, Oklahoma, United States
  • 1997-2002
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
  • 1995-2002
    • University of Michigan
      • Department of Pathology
      Ann Arbor, Michigan, United States
    • Catholic University of Korea
      Sŏul, Seoul, South Korea
  • 1991-1997
    • Pacific Institute of Bioorganic Chemistry
      Wladiwostok, Primorskiy, Russia
    • Russian Academy of Sciences
      Moskva, Moscow, Russia
  • 1996
    • Honolulu University
      Honolulu, Hawaii, United States