A5063647013- Complement system in diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Pancreatic function and diabetes
- Information Retrieval and Search Behavior
- Topic Modeling
- Retinal Diseases and Treatments
- Traumatic Brain Injury and Neurovascular Disturbances
- Thyroid Disorders and Treatments
- Trypanosoma species research and implications
- Parathyroid Disorders and Treatments
- Blood groups and transfusion
- Glycosylation and Glycoproteins Research
- Transplantation: Methods and Outcomes
- Neonatal and fetal brain pathology
- Acute Ischemic Stroke Management
- Metabolism, Diabetes, and Cancer
- S100 Proteins and Annexins
- Web Data Mining and Analysis
- Natural Language Processing Techniques
- Erythrocyte Function and Pathophysiology
- Research on Leishmaniasis Studies
- Organ Transplantation Techniques and Outcomes
- Renal Transplantation Outcomes and Treatments
- Spinal Cord Injury Research
Medical University of South Carolina
2016-2025
Ralph H. Johnson VA Medical Center
2016-2025
University of Roehampton
2024
Columbia University Irving Medical Center
1992-2023
MUSC Hollings Cancer Center
2013-2023
Guangxi Medical University
2023
First Affiliated Hospital of GuangXi Medical University
2023
University of Florida
1992-2020
Oxford University Press (United Kingdom)
2020
Bipar
2009-2018
Highly sensitive assays have been developed that enable 25-hydroxycholecalciferol (25-hydroxyvitamin D3) and 25-hydroxyergocalciferol D2) to be measured in the same serum sample. With these it has shown endogenously produced cholecalciferol (vitamin is important man; findings further emphasize role of vitamin D metabolites as hormones rather than vitamins traditional sense. Dietary sources appear inadequate deficiency cause rickets osteomalacia Asian immigrants Britain. This condition may...
Uncontrolled activation of the alternative pathway complement is thought to be associated with age-related macular degeneration (AMD). The continuously activated in fluid phase, and tissue surfaces require continuous inhibition prevent spontaneous autologous injury. Here, we examined effects oxidative stress on ability immortalized human retinal pigment epithelial cells (ARPE-19) regulate their cell surface. Combined treatment H2O2 (to induce stress) complement-sufficient serum was found...
purpose. Polymorphisms in factor H (fH), an inhibitor of the alternative pathway (AP) complement activation, are associated with increased risk for age-related macular degeneration (AMD). The authors investigated therapeutic use a novel recombinant form fH, CR2-fH, which is targeted to sites mouse choroidal neovascularization (CNV). CR2-fH consists N terminus contains AP-inhibitory domain, linked receptor 2 (CR2) targeting fragment that binds activation products. methods. Laser-induced CNV...
The complement system is implicated in promoting acute secondary injury after traumatic brain (TBI), but its role chronic post-traumatic neuropathology remains unclear. Using various injury-site targeted inhibitors that block different pathways and activation products, we investigated how involved neurodegeneration neuroinflammation TBI a clinically relevant setting of inhibition. current paradigm propagates post-TBI predominantly through the terminal membrane attack complex (MAC), focus has...
Local inhibition of complement activation after stroke in mice prevents degenerative microglial and improves chronic recovery.
Increasing evidence points to a role for the protein quality control in endoplasmic reticulum (ER) maintaining intestinal homeostasis. However, specific general ER chaperones this process remains unknown. Herein, we report that major heat shock grp94 interacts with MesD, critical chaperone Wnt coreceptor low-density lipoprotein receptor-related 6 (LRP6). Without grp94, LRP6 fails export from cell surface, resulting profound loss of canonical signaling. The significance finding is...
The acute lung injury (ALI) that occurs after the highly pathogenic avian influenza H5N1 virus infection is associated with an abnormal host innate immune response. Because complement system plays a central role in immunity and because aberrant activation variety of autoimmune inflammatory diseases, we investigated involvement pathogenesis ALI induced by infection. We showed H5N1-infected mice was caused excessive activation, as demonstrated deposition C3, C5b-9, mannose-binding lectin...
Dysregulation of the complement system is implicated in neurodegeneration, including human and animal glaucoma. Optic nerve retinal damage glaucoma preceded by local upregulation activation, but whether targeting this early innate immune response could have therapeutic benefit remains undefined. Because signals through three pathways that intersect at C3 here we targeted step to restore balance glaucomatous retina determine its contribution degeneration onset and/or progression. To achieve...
Abstract The Jumonji domain–containing chromatin remodeling factor JMJD3 has important roles in development and cancer. Here, we report a pivotal role for sustaining the phenotype of aggressive hepatocellular carcinomas. Expression levels clinical specimens carcinoma correlated inversely with patient survival. In cells, found that enforcing its overexpression induced epithelial–mesenchymal transition (EMT), invasive migration, stem cell–like traits, metastatic properties. Conversely,...
GARP encoded by the Lrrc32 gene is cell surface docking receptor for latent TGFβ, which expressed naturally platelets and regulatory T cells (Treg). Although amplified frequently in breast cancer, expression relevant functions of cancer have not been explored. Here, we report that exerts oncogenic effects, promoting immune tolerance enriching activating TGFβ tumor microenvironment. We found human breast, lung, colon cancers aberrantly. In genetic studies normal mammary gland epithelial...
ABSTRACT Natural resistance of humans to the cattle pathogen Trypanosoma brucei has been attributed presence in human serum nonimmune factors that lyse parasite. Normal contains two trypanosome lytic (TLFs). TLF1 is a 500-kDa lipoprotein, which reported contain apolipoprotein A-I (apoA-I), haptoglobin-related protein (Hpr), hemoglobin, paraoxonase, and apoA-II, whereas TLF2 larger, poorly characterized particle. We report here new immunoaffinity-based purification procedure for TLF1, as well...
The role of complement in antibody therapy cancer is general poorly understood. We used the EL4 syngeneic mouse model metastatic lymphoma to investigate immunotherapy directed against GD2, a target clinical relevance. IgG2a and IgM anti-GD2 protected EL4-challenged mice from metastases prolonged survival. Expression CD59, an inhibitor direct complement-mediated cytotoxicity (CMC), effectively cells CMC vitro but did not affect outcome monoclonal therapy. Protection by IgG was also unaffected...
Trypanosoma cruzi trypomastigotes acquire sialic acid (SA) from host glycoconjugates by means of a plasma membrane-associated trans-sialidase (TS). Here we study the substrate specificity TS, which differs all known sialyltransferases in that it does not require cytidine monophosphate (CMP)-SA as donor. The T.cruzi TS reversibly transfers SA to saccharides with terminal β-Gal (but α-Gal) residues. Donors are linked residues (α2-3), but (a2-6) bonds. type β-linkage Gal residue is minor...
Abstract Trypomastigotes of Trypanosoma cruzi, mammalian infective forms the parasite, express an unusual cell surface trans-sialidase. This enzyme enables parasite to rapidly sialylate its when supplied with alpha(2,3)-linked sialic acid from glycoconjugates in serum or on surfaces. Here we used a novel fluorescence-based, trypomastigote lysis assay evaluate role parasite's plasma membrane providing protection against complement cascade. were desialylated, and removal was confirmed by...
Abstract Bioavailability and therapeutic efficacy of soluble Crry, a mouse inhibitor all complement activation pathways, is significantly enhanced when linked to fragment receptor 2 (CR2), that targets C3 products. In this study, we characterize alternative pathway-specific inhibitors consisting single or dimeric N-terminal region factor H (fH; short consensus repeats 1–5) the same CR2 (CR2-fH CR2-fHfH). Both CR2-fH CR2-fHfH were highly effective at inhibiting pathway in vitro demonstrated...
Massive liver resection and small-for-size transplantation pose a therapeutic challenge, due to increased susceptibility of the remnant/graft ischemia reperfusion injury (IRI) impaired regeneration. We investigated dual role complement in IRI versus regeneration mice. Complement component 3 (C3) deficiency inhibition with receptor 2–complement 1–related protein y (CR2-Crry, an inhibitor C3 activation) provided protection from hepatic IRI, while also following partial hepatectomy (PHx),...
There is mounting evidence indicating an important role for complement in the pathogenesis of cerebral ischemia-reperfusion injury, or ischemic stroke. The alternative pathway stroke has not been investigated, and there conflicting data on terminal pathway. In this study, we show that compared with wild-type mice, mice deficient protein factor B treated inhibitor CR2-fH have improved outcomes after 60-min middle artery occlusion 24-h reperfusion. Factor B-deficient CR2-fH-treated were...