A5075817809- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Microtubule and mitosis dynamics
- Immune Cell Function and Interaction
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Atherosclerosis and Cardiovascular Diseases
- Inflammasome and immune disorders
- HIV Research and Treatment
- Immune cells in cancer
- Immunotherapy and Immune Responses
- Adipokines, Inflammation, and Metabolic Diseases
- Asthma and respiratory diseases
- IL-33, ST2, and ILC Pathways
- Immune responses and vaccinations
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Respiratory Support and Mechanisms
- Inflammation biomarkers and pathways
- MicroRNA in disease regulation
- Philosophy and Theoretical Science
- Invertebrate Immune Response Mechanisms
- Phenomenology and Existential Philosophy
- Autophagy in Disease and Therapy
- Galectins and Cancer Biology
- Vitamin C and Antioxidants Research
- Epistemology, Ethics, and Metaphysics
Canadian Respiratory Research Network
2023
Temple University
2013-2022
Louisiana State University Health Sciences Center Shreveport
2013
Lund University
2013
GlaxoSmithKline (United States)
2002-2010
Children's Hospital of Philadelphia
2008
Cytokinetics (United States)
2007
GlaxoSmithKline (United Kingdom)
2001-2002
University of Connecticut
1997
Centromere-associated protein-E (CENP-E) is a kinetochore-associated mitotic kinesin that thought to function as the key receptor responsible for checkpoint signal transduction after interaction with spindle microtubules. We have identified GSK923295, an allosteric inhibitor of CENP-E motor ATPase activity, and mapped binding site region similar bound by loop-5 inhibitors KSP/Eg5. Unlike these KSP inhibitors, which block release ADP destabilize motor-microtubule interaction, GSK923295...
Electronic cigarette (e-cig) use has recently been implicated in promoting atherosclerosis. In this study, we aimed to investigate the mechanism of e-cig exposure accelerated atherosclerotic lesion development. Approach and Results: Eight-week-old ApoE-/- mice fed normal laboratory diet were exposed vapor (ECV) for 2 hours/day, 5 days/week 16 weeks. We found that ECV significantly induced lesions as examined by Oil Red O staining greatly upregulated TLR9 (toll-like receptor 9) expression...
Background Goblet cell hyperplasia is a classic but variable pathologic finding in COPD. Current literature shows that smoking risk factor for chronic bronchitis the relationship of these clinical features to presence and magnitude large airway goblet has not been well described. We hypothesized current smokers bronchitics would have more cells than nonsmokers or those without (CB), independent airflow obstruction. Methods recruited 15 subjects with moderate severe COPD, 12 healthy smokers,...
Interleukin-19 (IL-19) is a putative Th2, anti-inflammatory interleukin. Its expression and potential role in atherogenesis are unknown. IL-19 not detected normal artery expressed to greater degree plaque from symptomatic versus asymptomatic patients, suggesting compensatory counter-regulatory function. We tested whether could reduce atherosclerosis susceptible mice identified plausible mechanisms.LDLR(-/-) fed an atherogenic diet injected with either 1.0 or 10.0 ng/g per day recombinant...
The ability of circulating monocytes to develop into lung macrophages and promote tissue damage depends upon their phenotypic pattern differentiation activation. Whether this varies with COPD severity is unknown. Here we characterize the activation status in patients moderate vs. severe COPD.Blood were isolated from normal non-smokers (14), current smokers (13), (9), (11). These cells subjected analysis by flow cytometry expression markers, chemoattractant receptors, surface markers...
Identification of biomarkers cigarette smoke -induced lung damage and early COPD is an area intense interest. Glucose regulated protein 78 kD (i.e., GRP78), a multi-functional which mediates cell responses to oxidant stress, increased in the lungs smokers serum subjects with COPD. We have suggested that secretion GRP78 by cells may explain increase To assess lung, we assayed bronchoalveolar lavage fluid (BALF) chronic non-smokers. also directly assessed acute effect material on isolated...
Chronic obstructive pulmonary disease (COPD) is characterized by an abnormal regulatory T cell (T(reg)) response and increases in helper type 1 (Th1) Th17 responses. It unclear if dysregulation of microRNAs (miRNA) within T(reg) cells contributes to the inflammatory COPD. In this study, we aimed compare miRNA profile COPD with that healthy controls explore function differentially expressed miRNAs. We first obtained effector (Teff ) from peripheral blood non-smokers, unaffected current...
There is a high incidence of tobacco use among intravenous opioid drug users. It well established that opioids and smoke induce degree immune activation, recent work suggests the combination these drugs promotes further activation system. Our approach involved treatment wild-type mice with cigarette (SM) for period eight weeks, chronic continuous administration morphine (M)
CD4+ regulatory T cells (Tregs) respond to environmental cues permit or suppress inflammation, and atherosclerosis weakens Treg suppression promotes plasticity. However, the effects of smoking plus morphine (SM + M) on plasticity remain unknown. To determine whether SM M helper 17 (Th17) cells, we analyzed RNA sequencing data from SM, M, treated Tregs performed knowledge-based IPA analysis. We demonstrated that (1) upregulated transcripts cytokines, chemokines, clusters differentiation (CDs)...
ABSTRACT Previous studies have demonstrated that KOR activation results in decreased susceptibility to infection by HIV-1 human PBMCs. In the present studies, we found this effect is, part, a result of down-regulation major coreceptor, CXCR4. Using combination biochemical approaches, our show CXCR4 protein and mRNA levels were reduced significantly following activation. We evaluated nature signaling pathway(s), which induced activation, using transcription factor-binding array analysis...
Chronic Obstructive Pulmonary Disease (COPD) is characterized by lung and systemic inflammation as well airway goblet cell hyperplasia (GCH). Mucin production activated in part stimulation of the epidermal growth factor (EGF) receptor pathway through neutrophils macrophages. How circulating cytokine levels relate to GCH not clear. We performed phlebotomy bronchoscopy on 25 subjects (six nonsmokers, 11 healthy smokers, eight COPD FEV1 30–60 %). Six endobronchial biopsies per subject were...
The cross-regulation of G protein-coupled receptors (GPCRs) plays an important role in the immune response. Studies from several laboratories have suggested that a hierarchy sensitivities to cross-desensitization exists for chemoattractant GPCRs. We carried out experiments study capacity formyl peptide receptor-1 (FPR1) desensitize chemokine CCR1 and CCR2. Our results show activation FPR1 resulted desensitization partial internalization CCR1, but not CCR2, both primary human monocytes HEK293...
Insects can effectively and rapidly clear microbial infections by a variety of innate immune responses including the production antimicrobial peptides. Induction these peptides in Drosophila has been well established to involve NF-kappaB elements. We present evidence here for molecular mechanism Lipopolysaccharide (LPS)-induced signaling involving NF-kappaB, RELISH, S2 cells. demonstrate that LPS induces rapid processing event within RELISH protein releasing C-terminal ankyrin-repeats from...
Sepsis is a leading cause of morbidity and mortality in intensive care units. Previously, we identified Protein Kinase C-delta (PKCδ) as an important regulator the inflammatory response sepsis. An issue development anti-inflammatory therapeutics risk immunosuppression inability to effectively clear pathogens. In this study, investigated whether PKCδ inhibition prevented organ dysfunction improved survival without compromising pathogen clearance. Sprague Dawley rats underwent sham surgery or...
Acutely, non-selective cannabinoid (CB) agonists have been shown to increase morphine antinociceptive effects, and we others also demonstrated that CB attenuate tolerance. Activation of CB2 receptors reverses allodynia hyperalgesia in models chronic pain, co-administration with receptor selective has be synergistic. activation reduce morphine-induced rodents, an effect attributed modulation inflammation. In the present set experiments, tested both acute interactions between agonist O-1966...
Background: The aetiology and inflammatory profile of combined pulmonary fibrosis emphysema (CPFE) remain uncertain currently. Objective: We aimed to examine the levels proteins in lung tissue a cohort patients with emphysema, interstitial (IPF), CPFE. Materials methods: Explanted lungs were obtained from subjects IPF, CPFE, (or normal subjects), extracts prepared. Thirty-four measured each section. Results: all 34 virtually indistinguishable IPF compared CPFE tissues, collectively,...
Abstract Tobacco smoking is common in HIV-infected patients, and prevalent among intravenous opiate abusers. Conversely, abusers are more likely HIV-infected, abuse associated with severe neuroinflammation. Given the coincident use of tobacco drug users (IVDUs), we set out to study effects smoke exposure, chronic morphine administration, HIV infection using NSG humanized mouse model. Our results show that smoke, morphine, combination promotes decline CD4 + T cells mice. Further,...