A5079112900- Complement system in diseases
- Phagocytosis and Immune Regulation
- Atherosclerosis and Cardiovascular Diseases
- Immune cells in cancer
- Platelet Disorders and Treatments
- Galectins and Cancer Biology
- Neuroinflammation and Neurodegeneration Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Reproductive System and Pregnancy
- Immune Response and Inflammation
- Inflammasome and immune disorders
- SARS-CoV-2 and COVID-19 Research
- Systemic Lupus Erythematosus Research
- Alzheimer's disease research and treatments
- Microplastics and Plastic Pollution
- Protein Interaction Studies and Fluorescence Analysis
- Immune Cell Function and Interaction
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Genomics, phytochemicals, and oxidative stress
- Pomegranate: compositions and health benefits
- Autophagy in Disease and Therapy
- Toxic Organic Pollutants Impact
- Glycosylation and Glycoproteins Research
- Sulfur Compounds in Biology
- Connexins and lens biology
California State University, Long Beach
2014-2020
University of California, Los Angeles
2019
Northern Arizona University
2016
University of California, Irvine
2006-2013
California State University System
2012
Cardiff University
2010
UC Irvine Health
2008
Beckman Research Institute
2004
City Of Hope National Medical Center
2004
University of Wales
2002-2003
The decline of cognitive function has emerged as one the greatest health threats old age. Age-related is caused by an impacted neuronal circuitry, yet molecular mechanisms responsible are unknown. C1q, initiating protein classical complement cascade and powerful effector peripheral immune response, mediates synapse elimination in developing CNS. Here we show that C1q levels dramatically increase normal aging mouse human brain, much 300-fold. This was predominantly localized close proximity...
Abstract Deficiency in C1q, the recognition component of classical complement cascade and a pattern receptor involved apoptotic cell clearance, leads to lupus-like autoimmune diseases characterized by auto-antibodies self proteins aberrant innate immune activation likely due impaired clearance cells. In this study, we developed an autologous system using primary human lymphocytes monocyte-derived macrophages (HMDMs) characterize effect C1q on macrophage gene expression profiles during uptake...
J. Neurochem. (2010) 112 , 733–743. Abstract The expression of C1q, a recognition molecule the complement system, is up‐regulated following neuronal injury and detected early in neurodegenerative disorders such as Alzheimer’s disease. This multimeric protein triggers an enhancement phagocytosis suboptimally opsonized targets by microglia, phagocytic cells CNS, similar to other phagocytes, enhances uptake apoptotic peripheral suppresses inflammatory cytokine production human monocytes,...
C1q, the first component of classical complement pathway, is also a pattern recognition receptor involved in and clearance apoptotic cells. C1q deficiency humans leads to development lupus-like autoimmune disease, it has been speculated that impaired cells may contribute disease development. Since phagocytes initiate specific appropriate immune responses as result initial ligand-receptor interactions, regulation gene expression by sculpting an response ingested "self-Ags." In this study,...
It has recently been recognized that the innate immune response, powerful first response to infection, significant influence in determining nature of subsequent adaptive response. C1q, mannose-binding lectin (MBL), and other members defense collagen family proteins are pattern recognition molecules, able enhance phagocytosis pathogens, cellular debris, apoptotic cells vitro vivo. Humans deficient C1q inevitably develop a lupus-like autoimmune disorder, studies knockout mice demonstrate...
Hypoxic–ischemic (HI) brain injury in infants is a leading cause of lifelong disability. We report novel pathway mediating oxidative after hypoxia–ischemia which C1q plays central role. Neonatal mice incapable classical or terminal complement activation because C6 deficiency pharmacologically inhibited assembly membrane attack complex were subjected to hypoxia–ischemia. Only −/− exhibited neuroprotection coupled with attenuated injury. This was associated reduced production reactive oxygen...
Abstract In the atherosclerotic lesion, macrophages ingest high levels of damaged modified low-density lipoproteins (LDLs), generating macrophage foam cells. Foam cells undergo apoptosis and, if not efficiently cleared by efferocytosis, can secondary necrosis, leading to plaque instability and rupture. As a component innate immune complement cascade, C1q recognizes opsonizes forms LDL, such as oxidized or acetylated promotes ingestion in vitro. was shown be protective an atherosclerosis...
Atherosclerosis is a chronic inflammatory disorder that characterized by the accumulation of modified lipoproteins in arterial intima. C1q and mannan-binding lectin (MBL) are not only recognition components involved activation inflammation via complement cascade, but they also able to directly modulate phagocyte activation. Studies C1q(-/-) MBL(-/-) mice suggest these molecules play protective role early atherosclerotic lesion absence of, or prior to, expression other components. However,...
Inappropriate activation of complement contributes to pathology in diverse inflammatory diseases. Soluble recombinant forms the natural cell membrane regulators are effective animal models and some human However, their use is limited for reasons related cost, short half lives, propensity cause unwanted systemic effects. Some these limitations may be overcome by bacterial expression systems, specific targeting moieties, judicious choice regulator. Here we describe application strategies...
The interaction of C1q with specific cells the immune system induces activities, such as enhancement phagocytosis in monocytes and stimulation superoxide production neutrophils. In contrast to some other monocyte activators, itself does not induce pro-inflammatory cytokine production, but rather inhibits lipopolysaccharide (LPS)-stimulated induction certain cytokines expression interleukin-10. To investigate molecular mechanism by which exerts this effect on gene expression, influence...
This study was designed to explore the effect of recombinant, membrane-targeted CD59 (rCD59-APT542) on growth and size fully developed neovascular complex using murine model laser-induced choroidal neovascularization (CNV). CNV induced by laser photocoagulation in C57BL/6 mice an argon laser, animals received rCD59-APT542 via intravitreal (ivt) route. Western blot analysis, immunohistochemistry, total complement hemolytic assay demonstrated that exogenously administered incorporated as well...
Self-assembling protein nanocapsules can be engineered for various bionanotechnology applications. Using the dodecahedral scaffold of E2 subunit from pyruvate dehydrogenase, we introduced non-native surface cysteines site-directed functionalization. The modified nanoparticle's structural, assembly, and thermostability properties were comparable to wild-type (E2-WT), after conjugation poly(ethylene glycol) (PEG) these cysteines, nanoparticle remained intact stable up 79.7 ± 1.8 °C. PEGylation...
We characterized the transcriptional effects of complement opsonization on foam cell formation in human monocyte-derived macrophages (HMDM). RNA-sequencing was used to identify pathways modulated by protein C1q during HMDM ingestion atherogenic lipoproteins oxidized low density lipoprotein (oxLDL) and acetylated (acLDL). All raw data were submitted MIAME-compliant database Gene Expression Omnibus (accession number GEO: GSE80442; http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE80442)....
Abstract C1q is an important recognition molecule of the innate immune response. It plays a dual role in vivo, triggering inflammation via activation classical complement pathway, to clear pathogens. However, it can also directly opsonize targets including apoptotic cells and damaged-self molecules, leading increased macrophage phagocytosis M2-like anti-inflammatory cytokine production. primarily synthesized by macrophages. Therefore we investigated production macrophages under various...
Inappropriate or unregulated activation of complement can contribute to pathology in inflammatory diseases. Previous studies have shown that soluble recombinant regulators are effective animal models and some human However, limitations include cost, rapid clearance, unwanted systemic effects. To avoid these problems, bacterial expression has been optimized methods for the addition a membrane-targeting moiety regulator developed. When administered directly sites inflammation,...
The higher-order architecture observed in biological systems, like viruses, is very effective nucleic acid transport. replications of this system has been attempted with both synthetic and naturally occurring polymers mixed results. Here we describe a peptide/siRNA quaternary complex that functions as an siRNA delivery system. rational design peptide assembly inspired by the viral capsids, but not derived from them. We selected collagen (COL) to provide structural stability folding...