A5046941357- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Systemic Lupus Erythematosus Research
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- Gene expression and cancer classification
- Chronic Lymphocytic Leukemia Research
- Immunodeficiency and Autoimmune Disorders
- Cytokine Signaling Pathways and Interactions
- Lymphoma Diagnosis and Treatment
- interferon and immune responses
- Bioinformatics and Genomic Networks
- Diabetes and associated disorders
- MicroRNA in disease regulation
- Congenital heart defects research
- Cancer-related molecular mechanisms research
- Glycosylation and Glycoproteins Research
- RNA modifications and cancer
- Gene Regulatory Network Analysis
- Neonatal Respiratory Health Research
- Neuropeptides and Animal Physiology
- Molecular Biology Techniques and Applications
- Galectins and Cancer Biology
- Circular RNAs in diseases
Oklahoma Medical Research Foundation
2007-2024
The University of Texas Southwestern Medical Center
2014-2024
Southwestern Medical Center
2012-2022
University of Oklahoma
2001-2007
Uniformed Services University of the Health Sciences
2006
University of Oklahoma Health Sciences Center
2005
University of Michigan–Ann Arbor
1995-2002
National Institute of Pathology
1998
Institute of Bioorganic Chemistry
1991-1997
Wake Research
1992-1995
MicroRNAs (miRNA) have emerged as an important new class of modulators gene expression. In this study we investigated miRNA that are differentially expressed in lupus nephritis. Microarray technology was used to investigate peripheral blood mononuclear cells (PBMCs) and Epstein-Barr Virus (EBV)-transformed cell lines obtained from nephritis affected patients unaffected controls. TaqMan-based stem-loop real-time polymerase chain reaction for validation. analysis both African American (AA)...
Abstract The failure of chemotherapeutic regimens to eradicate cancers often results from the outgrowth minor subclones with more dangerous genomic abnormalities or self-renewing capacity. To explore such intratumor complexities in B-cell chronic lymphocytic leukemia (CLL), we measured kinetics vivo by quantifying deuterium ( 2 H)-labeled cells as an indicator a cell that had divided. Separating CLL clones on basis reciprocal densities chemokine (C-X-C motif) receptor 4 (CXCR4) and cluster...
RAD51, a multifunctional protein, plays central role in DNA replication and homologous recombination repair, is known to be involved cancer development. We identified novel for RAD51 innate immune response signaling. Defects lead the accumulation of self-DNA cytoplasm, triggering STING-mediated after stress damage. In absence unprotected newly replicated genome degraded by exonuclease activity MRE11, fragmented nascent accumulates cytosol, initiating an response. Our data suggest that...
Targeted sequencing of sixteen SLE risk loci among 1349 Caucasian cases and controls produced a comprehensive dataset the variations causing susceptibility to systemic lupus erythematosus (SLE). Two independent disease association signals in HLA-D region identified two regulatory regions containing 3562 polymorphisms that modified thirty-seven transcription factor binding sites. These extensive functional are new potent facet HLA polymorphism. Variations modifying consensus motifs IRF4 CTCF...
Myeloid lineage cells use TLRs to recognize and respond diverse microbial ligands. Although unique transcription factors dictate the outcome of specific TLR signaling, whether lineage-specific differences exist further modulate quality TLR-induced inflammation remains unclear. Comprehensive analysis global gene in human monocytes, monocyte-derived macrophages, dendritic stimulated with various ligands identifies multiple lineage-specific, TLR-responsive programs. Monocytes are...
Significance Successful induction of protective immunity is critically dependent on our ability to design vaccines that can induce dendritic cell (DC) maturation. Here, we investigated the mechanisms by which Toll-like receptor 4 (TLR4) and TLR3 DC We discovered TLR4 recognizes LPS from Gram-negative bacteria uses signaling adaptor Toll–IL-1 domain-containing inducing IFN-β robust activation NF-κB MAP kinases directly lead transcription genes necessary for However, viral RNA depends...
Abstract Motivation: We face the absence of optimized standards to guide normalization, comparative analysis, and interpretation data sets. One aspect this is that current methods statistical analysis do not adequately utilize information inherent in large sets generated a microarray experiment require tradeoff between detection sensitivity specificity. Results: present multistep procedure for mRNA expression obtained from cDNA array methods. To identify classify differentially expressed...
Objectives . Serum cytokines play an important role in the pathogenesis of psoriatic arthritis (PsA) by initiating and perpetuating various cellular humoral autoimmune processes. The aim this study was to describe a broad spectrum T- B-cell cytokines, growth factors chemokines patients with PsA healthy individuals. Methods A novel protein array system, denoted as multiplex cytokine assay utilized measure simultaneously levels 23 circulating Additionally, correlational clustering discriminant...
Serum cytokines play an important role in the pathogenesis of myositis by initiating and perpetuating various cellular humoral autoimmune processes. The aim present study was to describe a broad spectrum T- B-cell cytokines, growth factors chemokines patients with idiopathic inflammatory myopathies (IIMs) healthy individuals.A protein array system, denoted as multiplex cytokine assay utilized measure simultaneously levels 24 circulating including activating factor (BAFF) proliferation...
Abstract Sle1c is a sublocus of the NZM2410-derived Sle1 major lupus susceptibility locus. We have shown previously that contributes to pathogenesis by conferring increased CD4+ T cell activation and chronic graft-versus-host disease (cGVHD), which mapped centromeric portion In this study, we refined 675-kb interval, termed Sle1c2. Mice from recombinant congenic strains expressing Sle1c2 exhibited intrinsic cGVHD susceptibility, similar mice with parental Sle1c. addition, B6.Sle1c2 displayed...
Juvenile rheumatoid arthritis (JRA) has a complex, poorly characterized pathophysiology. Modeling of transcriptosome behavior in pathologic specimens using microarrays allows molecular dissection complex autoimmune diseases. However, conventional analyses rely on identifying statistically significant differences gene expression distributions between patients and controls. Since the principal aspects disease pathophysiology vary significantly among patients, these are biased. Genes with...
Abstract Although strong epidemiologic evidence suggests an important role for adaptive immunity in the pathogenesis of polyarticular juvenile rheumatoid arthritis (JRA), there remain many aspects disease that suggest equally contributions innate immune system. We used gene expression arrays and computer modeling to examine function neutrophils 25 children with JRA. Computer analysis identified 712 genes were differentially expressed between patients healthy controls. Computer-assisted...
We report on 2 patients with compound heterozygous mutations in forkhead box N1 (FOXN1), a transcription factor essential for thymic epithelial cell (TEC) differentiation. TECs are critical T development. Both had presentation consistent T–/loB+NK+ SCID, normal hair and nails, distinct from the classic nude/SCID phenotype individuals autosomal-recessive FOXN1 mutations. To understand basis of this effects FOXN1, we generated mice using CRISPR-Cas9 technology to genocopy 1 patients. The Foxn1...
The forkhead DNA-binding protein FOXP3 is critical for the development and suppressive function of CD4(+)CD25(+) regulatory T cells (T(REG)), which play a key role in maintaining self-tolerance. Functionally, capable repressing transcription cytokine genes regulated by NFAT. Various mechanisms have been proposed mediates these effects. Using novel cell lines that inducibly express either wild-type or mutant FOXP3, we identified NFAT2 as an early target FOXP3-mediated transcriptional...
Sle1a.1 is part of the Sle1 susceptibility locus, which has strongest association with lupus nephritis in NZM2410 mouse model. In this study, we show that results production activated and autoreactive CD4(+) T cells. Additionally, expression reduces peripheral regulatory cell pool, as well induces a defective response cells to retinoic acid expansion TGF-β-induced At molecular level, corresponds an increased novel splice isoform Pbx1, Pbx1-d. Pbx1-d overexpression sufficient induce...
Abstract Sle2c1 is an NZM2410- and NZB-derived lupus susceptibility locus that induces expansion of the B1a cell compartment. cells have a repertoire enriched for autoreactivity, this B subset occurs in several mouse models lupus. A combination genetic mapping candidate gene analysis presents Cdkn2c, encoding cyclin-dependent kinase inhibitor p18INK4c (p18), as top inducing Slec2c1-associated cells. novel single nucleotide polymorphism NZB allele Cdkn2c promoter associated with significantly...