A5052226943- Immune cells in cancer
- Mycobacterium research and diagnosis
- Immunotherapy and Immune Responses
- Phagocytosis and Immune Regulation
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Tuberculosis Research and Epidemiology
- T-cell and B-cell Immunology
- Leprosy Research and Treatment
- Cancer Immunotherapy and Biomarkers
- Legionella and Acanthamoeba research
- Vibrio bacteria research studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Virus-based gene therapy research
- Ubiquitin and proteasome pathways
- Veterinary medicine and infectious diseases
- Mesenchymal stem cell research
- Microbial infections and disease research
- Glycosylation and Glycoproteins Research
- Cytomegalovirus and herpesvirus research
- Infectious Diseases and Mycology
- Carbohydrate Chemistry and Synthesis
- Immunodeficiency and Autoimmune Disorders
- Herpesvirus Infections and Treatments
- Infectious Diseases and Tuberculosis
Colorado State University
2016-2025
New Mexico State University
2018
University of Colorado Denver
1993-2010
Infectious Disease Research Institute
2010
Denver Health Medical Center
2010
Centers for Disease Control and Prevention
2010
University of Colorado Health
2004-2005
National Jewish Health
1993-2005
Zero to Three
2004
University of Washington
1999
Tumor-associated macrophages (TAMs) express programmed cell death ligand 1 (PD-L1) and contribute to the immune-suppressive tumor microenvironment. Although role of PD-L1 PD-1 interaction regulate T-cell suppression is established, less known about signaling in how these signals may affect function TAMs. We used vitro vivo models investigate effects antibody treatment on TAM responses. Treatment mouse human with antibodies increased spontaneous macrophage proliferation, survival, activation...
Cyclic AMP (cAMP)-dependent protein kinase A (PKA) stimulates the transcription of many eucaryotic genes by catalyzing phosphorylation cAMP-regulatory element binding (CREB). Conversely, attenuation or inhibition cAMP-stimulated gene would require dephosphorylation CREB a nuclear phosphatase. In HepG2 cells treated with serine/threonine (Ser/Thr) phosphatase inhibitor okadaic acid, dibutyryl-cAMP-stimulated from phosphoenolpyruvate carboxykinase (PEPCK) promoter was enhanced over level PEPCK...
The paired box transcription factor Pax-5 (B-cell-specific activator protein) is a key regulator of lineage-specific gene expression and differentiation in B-lymphocytes. We show that functions as cell type-specific docking protein facilitates binding the early B-cell-specific mb-1 promoter by proteins Ets proto-oncogene family. Transcriptional activity pre-B-cells critically dependent on sites for Pax-5:Ets complexes. Ternary complex assembly requires only ETS DNA-binding domains. Mutation...
Abstract Background The currently well-established humanized mouse models, namely the hu-PBL-SCID and SCID-hu systems played an important role in HIV pathogenesis studies. However, despite many notable successes, several limitations still exist. They lack multi-lineage human hematopoiesis a functional immune system. These models primarily reflect acute infection with rapid CD4 T cell loss thus limiting studies to short-term period. new Rag2 -/- γc model (RAG-hu) created by intrahepatic...
Cellular therapy with allogeneic or autologous mesenchymal stem cells (MSC) has emerged as a promising new therapeutic strategy for managing inflammatory bowel disease (IBD). However, MSC ideally requires convenient and relatively homogenous cell source (typically bone marrow adipose tissues) the ability to generate stable phenotype function. An alternative means of generating is derive them from induced pluripotent (iPSC), which could in theory provide an indefinite supply well-defined...
Patients who have common variable immunodeficiency (CVID) and granulomatous/lymphocytic interstitial lung disease (GLILD) are at high risk for early mortality B cell lymphomas. Infection with human herpes virus type 8 (HHV8), a lymphotrophic virus, is linked to lymphoproliferative disorders in people secondary immunodeficiencies. Therefore, we determined the prevalence of HHV8 infection CVID patients GLILD. Genomic DNA isolated from peripheral blood mononuclear cells was screened by nested-...
Leprosy is a curable neglected disease of humans caused by Mycobacterium leprae that affects the skin and peripheral nerves manifests clinically in various forms ranging from self-resolving, tuberculoid leprosy to lepromatous having significant pathology with ensuing disfiguration disability social stigma. Despite global success multi-drug therapy (MDT), incidences clinical have been observed individuals no apparent exposure other cases, suggestive possible non-human sources bacteria. In...
Abstract The canine spontaneous cancer model is increasingly utilized to evaluate new combined immunotherapy approaches. While the major leukocyte subsets and phenotypes are closely related in dogs humans, functionality of T cells antigen presenting two species has not been previously compared detail. Such information would be important interpreting immune response data evaluating potential toxicities immunotherapies dogs. To address this question, we used vitro assays compare...
Mycobacterium abscessus is increasingly recognized as the causative agent of chronic pulmonary infections in humans. One genes found to be under strong evolutionary pressure during adaptation M. human lung embC which encodes an arabinosyltransferase required for biosynthesis cell envelope lipoglycan, lipoarabinomannan (LAM). To assess impact patient-derived mutations on physiology and virulence , were introduced isogenic background ATCC 19977 resulting strains probed phenotypic changes a...
ABSTRACT A simple serodiagnostic test based on the Mycobacterium leprae -specific phenolic glycolipid I(PGL-I), for individuals with leprosy is nearly universally positive in patients high bacillary loads but cannot be used as a stand-alone diagnostic entire spectrum of disease process. For early infection no detectable acid-fast bacilli lesions or low antibody titer to PGL-I, those at tuberculoid end spectrum, this approach has limited usefulness. To identify additional M. antigens that...
Although leprosy is curable with drug treatment, the identification of biomarkers infection, disease progression and treatment efficacy would greatly help to reduce overall prevalence disease. Reliable also incidence grade-2 disability by ensuring that those who are most at risk diagnosed treated early or offered repeated treatments in case relapse. In this study, we examined reactivity sera from lepromatous tuberculoid patients (LPs) against a panel 12 recombinant Mycobacterium leprae...
Mesenchymal stem cells (MSCs) exhibit broad immune modulatory activity in vivo and can suppress T cell proliferation dendritic activation vitro. Currently, most MSC for clinical usage are derived from younger donors, due to ease of procurement the superior activity. However, use multiple unrelated donors makes it difficult standardize study results compare outcomes between different trials. One solution is induced pluripotent (iPSC); as iPSC-derived have nearly unlimited proliferative...
Cyclic AMP (cAMP)-dependent protein kinase A (PKA) stimulates the transcription of many eucaryotic genes by catalyzing phosphorylation cAMP-regulatory element binding (CREB). Conversely, attenuation or inhibition cAMP-stimulated gene would require dephosphorylation CREB a nuclear phosphatase. In HepG2 cells treated with serine/threonine (Ser/Thr) phosphatase inhibitor okadaic acid, dibutyryl-cAMP-stimulated from phosphoenolpyruvate carboxykinase (PEPCK) promoter was enhanced over level PEPCK...
ABSTRACT Mycobacterium leprae induces the formation of lipid droplets, which are recruited to pathogen-containing phagosomes in infected macrophages and Schwann cells. Cholesterol is among lipids with increased abundance M. -infected cells, intracellular survival relies on cholesterol accumulation. The present study investigated capacity acquire metabolize cholesterol. In silico analyses showed that oxidation cholest-4-en-3-one (cholestenone), first step degradation catalyzed by enzyme...
Mesenchymal stem cells (MSC) represent a readily accessible source of with potent immune modulatory activity. MSC can suppress ongoing inflammatory responses by suppressing T cell function, while fewer studies have examined the impact on dendritic (DC) function. The dog spontaneous disease model represents an important animal which to evaluate safety and effectiveness cellular therapy MSC. This study evaluated effects canine activation maturation monocyte-derived DC, as well mechanisms...
Like other tuberculous and nontuberculous mycobacterial pathogens of human lung such as Mycobacterium tuberculosis M. abscessus, avium is likely exposed to a variety stressors during infection, including hypoxic conditions inside activated macrophages in the avascular necrotic regions granulomas. How survives stress establish chronic infection currently not well understood. Using RNA-sequencing, we here show that grown under progressive microaerophilic activates more than 4-fold subset 16...
ABSTRACT Mycobacterium abscessus is one of the leading causes pulmonary infections caused by non-tuberculous mycobacteria. The ability M. to establish a chronic infection in lung relies on series adaptive mutations impacting, part, global regulators and cell envelope biosynthetic enzymes. One genes under strong evolutionary pressure during host adaptation ubiA , which participates elaboration arabinan domains two major polysaccharides: arabinogalactan (AG) lipoarabinomannan (LAM). We here...
Mycobacterium abscessus is a rapidly growing nontuberculous causing severe pulmonary infections, especially in immunocompromised individuals and patients with underlying lung conditions like cystic fibrosis (CF). While rifamycins are the pillar of tuberculosis treatment, their efficacy against M. disease severely compromised by intrabacterial ADP-ribosylation. Additionally, induce cytochrome P450 3A4 (CYP3A4), major human drug-metabolizing enzyme, further limiting use comorbidities that...
Pax family transcription factors bind DNA through the paired domain. This domain, which is comprised of two helix-turn-helix motifs and a β-hairpin structure, target mutations in congenital disorders mice humans. Previously, we showed that Pax-5 (B-cell-specific activator protein) recruits proteins Ets proto-oncogene to composite site essential for efficient early-B-cell-specificmb-1 promoter. Here, evidence provided specific interactions between Ets-1 amino-terminal subdomains proteins. By...
Type 1 diabetes results from the breakdown of peripheral tolerance. As regulators T cell activation, antigen-presenting cells (APC) modulate tolerance and hence contribute to immune dysregulation characteristic insulin-dependent mellitus (IDDM). We initially observed an increased importance NOD B APC function in a priming assay as compared non-autoimmune strains. Consistent with this function, we found that NF-kappa nuclear translocation is unmanipulated NOD.B10Sn-H2(b) that, addition, are...
Two lipoglycans, lipomannan (LM) and lipoarabinomannan (LAM), play various, albeit incompletely defined, roles in the interactions of mycobacteria with host. Growing evidence points to modification LM LAM discrete covalent substituents as a strategy used by these bacteria modulate their biological activities. One such substituent, originally identified Mycobacterium tuberculosis (Mtb), is 5-methylthio-d-xylose (MTX) sugar, which accounts for antioxidative properties LAM. The widespread...
We report that the small tumor (small-t) antigen of simian virus 40 (SV40) forms complexes with nuclear protein phosphatase 2A (PP2A) and regulates phosphorylation transcriptional transactivation function cyclic AMP (cAMP)-regulatory element binding (CREB). PP2A coimmunoprecipitated t from extracts HepG2 cells expressing or rat liver to which recombinant was added. Protein 1 not detected in small-t immunoprecipitates. In t, dibutyryl-cAMP (Bt2cAMP) stimulated CREB 65-fold, whereas only 5-...
C5-deficient mice differed from C5-sufficient both quantitatively and qualitatively in C5 protein, mRNA, the gene. protein was present as decreased amounts of an unprocessed, single-chain precursor. mRNA amount two forms, smaller which same single form normal cells. Nuclei deficient cells contained larger DNA demonstrated differences pattern on Southern analysis for restriction enzymes. These data suggest that primary transcript gene is abnormal, retarding processing codes abnormal protein.