A5085500578- Complement system in diseases
- Renal Diseases and Glomerulopathies
- Immunotherapy and Immune Responses
- Systemic Lupus Erythematosus Research
- Monoclonal and Polyclonal Antibodies Research
- Adenosine and Purinergic Signaling
- Blood Coagulation and Thrombosis Mechanisms
- Phagocytosis and Immune Regulation
- S100 Proteins and Annexins
- Renal Transplantation Outcomes and Treatments
- Dialysis and Renal Disease Management
- Pregnancy and preeclampsia studies
- Vasculitis and related conditions
- Extracellular vesicles in disease
- Immune Cell Function and Interaction
- Platelet Disorders and Treatments
- COVID-19 Impact on Reproduction
- Peptidase Inhibition and Analysis
- Biomarkers in Disease Mechanisms
- Historical Medical Research and Treatments
- Endoplasmic Reticulum Stress and Disease
- Cancer Mechanisms and Therapy
- interferon and immune responses
- Angiogenesis and VEGF in Cancer
- Acute Kidney Injury Research
University of Colorado Denver
2015-2023
University of Colorado Anschutz Medical Campus
2016-2023
RELX Group (United States)
2017
University of Colorado Health
2016
The complement cascade is a part of the innate immune system that acts primarily to remove pathogens and injured cells. However, activation also peculiarly associated with tumor progression. Here we report mechanistic insights into this association in multiple immunocompetent orthotopic models lung cancer. After engraftment, observed systemic as reflected by elevated levels key regulator C3a. Notably, growth primary tumors metastases was both strongly inhibited C3-deficient mice (C3-/-...
Hepatocellular carcinoma (HCC) is difficult to detect, carries a poor prognosis, and one of few cancers with an increasing yearly incidence. Molecular defects in complement factor H (CFH), critical regulatory protein the alternative pathway (AP), are typically associated inflammatory diseases eye kidney. Little known regarding role CFH controlling activation within liver. While studying aging CFH-deficient (fH–/–) mice, we observed spontaneous hepatic tumor formation more than 50% aged fH–/–...
Background Endothelial microparticles are associated with chronic kidney disease ( CKD ) and complement activation. We hypothesized that the pathway is activated in patients via endothelial activation correlates dysfunction . Methods Results analyzed data of 30 healthy subjects, stage III / IV , renal transplant recipients evaluating potential correlation fragments brachial artery flow–mediated dilation, Chronic Kidney Disease Epidemiology Collaboration glomerular filtration rate, urinary...
Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) are common forms of idiopathic nephrotic syndrome. The causes these diseases incompletely understood, but the response patients to immunosuppressive therapies suggests that their pathogenesis is at least in part immune mediated. Preclinical clinical research indicates activation classical pathway complement contributes glomerular injury FSGS. Glomerular IgM deposits also prominent some patients, raising possibility a...
Abstract Cardiovascular disease (CVD) is the most common cause of death in patients with native and post-transplant chronic kidney (CKD). To identify new biomarkers vascular injury inflammation, we analyzed proteome plasma circulating extracellular vesicles (EVs) CKD utilizing an aptamer-based assay. Proteins angiogenesis were significantly higher versus healthy controls. Ingenuity pathway analysis (IPA) indicated Ephrin receptor signaling, serine biosynthesis, transforming growth factor-β...
Complement factor H-related protein 1 (CFHR1) is a complement regulator which has been reported to regulate by blocking C5 convertase activity and interfering with C5b surface association. CFHR1 also competes H (CFH) for binding C3b, may act as an antagonist of CFH-directed regulation on cell surfaces. We have employed site-directed mutagenesis in conjunction ELISA-based functional assays isolate the interaction that undertakes components C3b C3d single shared interface. The C3b/C3d:CFHR1...
In vivo, cancer cells respond to signals from the tumor microenvironment resulting in changes expression of proteins that promote progression and suppress anti-tumor immunity. This study employed an orthotopic immunocompetent model lung define pathways are altered recovered tumors compared grown culture. Studies used four murine cell lines implanted into lungs syngeneic mice. Cancer were using FACS, transcriptional culture determined by RNA-seq. Changes interferon response, antigen...
Abstract Factor H is a circulating protein that regulates activation of the alternative pathway (AP) complement. Mutations and genetic variations factor are associated with several AP-mediated diseases, highlighting critical role in AP regulation. inflammation typically triggered by illness or tissue injury, however, injury can trigger individuals fully functional H. This suggests function affected local conditions within tissues. We hypothesized inducible proteins impair ability to locally...
Humoral autoimmunity is central to the development of systemic lupus erythematosus (SLE). Complement receptor type 2 (CR2)/CD21 plays a key role in high-affinity Abs and long-lasting memory foreign Ags. When CR2 bound by its primary C3 activation fragment-derived ligand, designated C3d, it coassociates with CD19 on B cells amplify BCR signaling. C3d also mediate immune complex binding follicular dendritic cells. As SLE involves subversion normal cell tolerance checkpoints, one might expect...
Natural IgM binds to glomerular epitopes in several progressive kidney diseases. Previous work has shown that also within the glomerulus after ischemia/reperfusion (I/R) but does not fully activate complement system. Factor H is a circulating regulatory protein, and congenital or acquired deficiency of factor strong risk for types disease. We hypothesized controls activation by I/R, heterozygous would permit IgM-mediated injury at this location. found mice with targeted deletion gene...
Experiments in mouse models have shown that the complement cascade is activated within kidney after ischemia-reperfusion and activation contributes to tubular injury this setting. Less known, however, about human kidneys ischemia or whether tubulointerstitium can be detected by measurement of fragments urine. We hypothesized urine biomarkers would rapidly increase patients who develop ischemic acute injury, signaling kidney. confirmed alternative pathway mice ischemia-reperfusion, we found...
Significance Statement Histologic quantification of complement C3 deposits in kidney biopsies provides prognostic information patients with glomerulonephritis. Unfortunately, are invasive procedures that cannot be performed regularly and only provide a snapshot small portion one at the time sampling. We have developed method to noninvasively detect specific fragment deposition throughout both kidneys, using monoclonal antibody targeting tissue-bound iC3b/C3d linked bioluminescent resonance...
Abstract Background: The complement system is an important arm of the innate immune system, and proteins are produced by both cancer cells TME. A primary function to remove pathogens injured cells, it had been assumed that activation would result in elimination cells. However, recent work has revealed new biologic effects fragments C3a C5a. For example, C5a directly stimulate growth some tissues. Furthermore, inflammatory as well CD4 CD8 T express receptors for these (C3aR C5aR), a study...