- Atherosclerosis and Cardiovascular Diseases
- Systemic Lupus Erythematosus Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune cells in cancer
- interferon and immune responses
- Inflammasome and immune disorders
- Cholesterol and Lipid Metabolism
- Cytokine Signaling Pathways and Interactions
- Immune Response and Inflammation
- Cardiovascular Disease and Adiposity
- Nonmelanoma Skin Cancer Studies
- Immunodeficiency and Autoimmune Disorders
- Cutaneous Melanoma Detection and Management
- Fish biology, ecology, and behavior
- Contact Dermatitis and Allergies
- Hedgehog Signaling Pathway Studies
- Asthma and respiratory diseases
- NF-κB Signaling Pathways
- Cell death mechanisms and regulation
- Identification and Quantification in Food
- Eosinophilic Disorders and Syndromes
- Adipokines, Inflammation, and Metabolic Diseases
- Antioxidant Activity and Oxidative Stress
- Sphingolipid Metabolism and Signaling
- Lipoproteins and Cardiovascular Health
Cedars-Sinai Medical Center
2016-2024
Semtech (United States)
2024
Center for Rheumatology
2021
University of California, San Diego
2011-2016
Austrian Academy of Sciences
2011
Medical University of Vienna
2011
Systemic Lupus Erythematosus (SLE) is a chronic inflammatory autoimmune disease in which type I interferons (IFN) play key role. The IFN response can be triggered when oxidized DNA engages the cytosolic sensing platform cGAS-STING, but repair mechanisms that modulate this process and govern progression are unclear. To gain insight into biology, we interrogated role of oxyguanine glycosylase 1 (OGG1), repairs guanine 8-Oxo-2′-deoxyguanosine (8-OH-dG), pristane-induced mouse model SLE. Ogg1-/-...
Immunization with homologous malondialdehyde (MDA)-modified LDL (MDA-LDL) leads to atheroprotection in experimental models supporting the concept that a vaccine oxidation-specific epitopes (OSEs) of oxidized could limit atherogenesis. However, modification human OSE use as an immunogen would be impractical for generalized use. Furthermore, when MDA is used modify LDL, wide variety related adducts are formed, both simple and more complex. To define relevant reproduce atheroprotective effects...
Severe lung inflammation and alveolar hemorrhage can be life-threatening in systemic lupus erythematosus (SLE) patients if not treated early aggressively. Neutrophil influx is the driver key of this pathology, but little known regarding molecular events regulating recruitment. Here, we uncover a role for IL-16/mir-125a pathology show only that IL-16 target miR-125a reduced expression SLE associates with involvement. Furthermore, pristane model acute "SLE-like" hemorrhage, observed pulmonary...
Diffuse alveolar hemorrhage (DAH), although rare, is a life-threatening complication of systemic lupus erythematosus (SLE). Little known about the pathophysiology DAH in humans, increasingly neutrophils, NETosis and inflammatory monocytes have been shown to play an important role pristane-induced model SLE which develops lung recapitulates many pathologic features human DAH. Using this experimental model, we asked whether endoplasmic reticulum (ER) stress played driving pathology pulmonary...
Effective therapies to reduce the severity and high mortality of pulmonary vasculitis diffuse alveolar hemorrhage (DAH) in patients with systemic lupus erythematosus (SLE) is a serious unmet need. We explored whether biologic neutralization eNAMPT (extracellular nicotinamide phosphoribosyl-transferase), novel DAMP Toll-like receptor 4 ligand, represents viable therapeutic strategy vasculitis.
Objective We aimed to investigate the hypothesis that interferon (IFN)–stimulated gene (ISG) expression in systemic lupus erythematosus (SLE) monocytes is linked changes metabolic reprogramming and epigenetic regulation of ISG expression. Methods Monocytes from healthy volunteers patients with SLE at baseline or following IFNα treatment were analyzed by extracellular flux analysis, proteomics, metabolomics, chromatin immunoprecipitation, The histone demethylases KDM6A/B inhibited using...
Skin cancer risk is increased by exposure to ultraviolet radiation (UVR). Because UVR accumulates over time and lighter skin more susceptible UVR, age tone are factors for cancer. However, measurements of somatic mutations in healthy-appearing have not been used calculate risk. In this study, we developed a noninvasive test that quantifies sun-exposed applied it 1038-subject cohort. Somatic were combined with other known train model The final (DNA-Skin Cancer Assessment Risk) was trained...
Macrophages play a key role in atherogenesis part through excessive uptake of oxidized LDL (OxLDL) via scavenger receptors. Binding OxLDL to macrophages has traditionally been assessed using radiolabeled OxLDL. To allow more efficient and convenient measurements, we developed nonradioactive binding assay which biotinylated (Bt-OxLDL) is added 96-well microtiter culture plates under various conditions the extent determined solid phase chemiluminescent immunoassay techniques. As examples, show...
Background: Women with SLE have an elevated risk of CVD morbidity and mortality frequently report chest pain in the absence obstructive CAD. Echocardiographic studies often demonstrate reduced LV function, correlating higher disease activity. We used cardiac MRI (cMRI) to investigate relationship between SLE, related inflammatory biomarkers function female patients.
Macrophage scavenger receptors appear to play a major role in the clearance of oxidized phospholipid (OxPL) products. Discrete peptide-phospholipid conjugates with phosphatidylcholine headgroup have been shown exhibit binding affinity for these receptors. We report preparation water-soluble, stable conjugate (9) that possesses necessary physical properties enable more detailed study role(s) OxPL metabolic disease.
Women with SLE have an elevated risk of cardiovascular disease. Many women frequently report chest pain in the absence obstructive coronary artery disease (CAD) due to microvascular dysfunction (CMD), a form ischemia no CAD. Echocardiographic studies shown that patients reduced left ventricular (LV) function, which may also correlate higher activity scores. As such, we used cardiac magnetic resonance imaging (cMRI) investigate relationship between SLE, related inflammatory biomarkers, and...
Abstract Objective To investigate whether gene signatures discriminate systemic lupus erythematosus (SLE) patients with coronary microvascular dysfunction (CMD) from those without and any signaling pathway is linked to the underlying pathobiology of SLE CMD. Methods This study collected whole blood RNA samples female subjects aged 37 57, comprising 11 (4 SLE-CMD, 7 SLE-non-CMD) 10 HC. Total was then used for library preparation sequencing. Differential expression analysis performed identify...
Systemic lupus erythematosus (SLE) patients are 90% women and over three times more likely to die of cardiovascular disease than in the general population. Chest pain with no obstructive cardiac is associated coronary microvascular (CMD), where narrowing small blood vessels can lead ischemia, frequently reported by SLE patients. Using whole RNA samples, we asked whether gene signatures discriminate dysfunction (CMD) on MRI (n=4) from those without (n=7) any signaling pathway linked...
Innate immunity utilizes evolutionarily conserved pattern recognition receptors (PRRs) to provide an early and effective response against Pathogen-Associated Molecular Patterns (PAMPs) on microbial pathogens and/or Danger Associated (DAMPs) endogenous modified-self structures. Atherosclerosis is a chronic inflammatory disease in which lipid peroxidation greatly increased leading the generation of OxLDL, contains variety proinflammatory oxidation-specific neoepitopes (OSE), such as...
<h3></h3> The authors have declared that no conflict of interest exists. <h3>Objective</h3> To investigate the hypothesis interferon (IFN) stimulated gene (ISG) expression in systemic lupus erythematosus (SLE) monocytes is linked to changes metabolic reprogramming and epigenetic regulation ISG expression. <h3>Methods</h3> Monocytes from healthy volunteers SLE patients at baseline or following IFNα treatment were analyzed by extracellular flux analysis, proteomics, metabolomics, chromatin...
Abstract Diffuse alveolar hemorrhage (DAH), although rare, is a life-threatening complication of systemic lupus erythematosus (SLE). Little known about the pathophysiology DAH in humans, increasingly neutrophils, NETosis and inflammatory monocytes have been shown to play an important role pristane-induced model SLE which develops lung recapitulates many pathologic features human DAH. Using this experimental model, we asked whether endoplasmic reticulum (ER) stress played driving pathology...