A5077468407- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Mosquito-borne diseases and control
- interferon and immune responses
- Renal Transplantation Outcomes and Treatments
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
- Phagocytosis and Immune Regulation
- Immune cells in cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Psoriasis: Treatment and Pathogenesis
- Reproductive System and Pregnancy
- Viral Infections and Vectors
- Cytomegalovirus and herpesvirus research
- Celiac Disease Research and Management
- Whipple's Disease and Interleukins
- Malaria Research and Control
- Nanowire Synthesis and Applications
- RNA regulation and disease
- HIV Research and Treatment
- Cytokine Signaling Pathways and Interactions
- Chemokine receptors and signaling
- Multiple Sclerosis Research Studies
Northwestern University
2013-2022
The University of Sydney
2006-2022
Astellas Pharma (United States)
2018-2021
Pharmac
2020
Oncotherapeutics (United States)
2019
Pharmaceutical Product Development (United States)
2014-2015
Northwestern University
2014
Kalamazoo College
2010
Robert Bosch (Australia)
2009
Negatively charged immune-modifying microparticles bind to the scavenger receptor MARCO on inflammatory monocytes, resulting in their apoptosis and reduced damage a range of diseases.
In a lethal West Nile virus (WNV) model, central nervous system infection triggered threefold increase in CD45(int)/CD11b(+)/CD11c(-) microglia at days 6-7 postinfection (p.i.). Few were proliferating, suggesting that the increased numbers derived from migratory precursor cell. Depletion of "circulating" (Gr1(-)(Ly6C(lo))CX3CR1(+)) and "inflammatory" (Gr1(hi)/Ly6C(hi)/CCR2(+)) classical monocytes during abrogated microglia. C57BL/6 chimeras reconstituted with cFMS-enhanced green fluorescent...
Targeted immune tolerance is a coveted therapy for the treatment of variety autoimmune diseases, as current options often involve nonspecific immunosuppression. Intravenous (iv) infusion apoptotic syngeneic splenocytes linked with peptide or protein autoantigens using ethylene carbodiimide (ECDI) has been demonstrated to be an effective method inducing peripheral, antigen-specific disease. Here, we show ability biodegradable poly(lactic-co-glycolic acid) (PLG) nanoparticles function safe,...
Abstract T cells expressing CD19-targeting chimeric antigen receptors (CARs) reveal high efficacy in the treatment of B cell malignancies. Here, we report that receptor fusion constructs (TRuCs) comprising an antibody-based binding domain fused to (TCR) subunits can effectively reprogram intact TCR complex recognize tumor surface antigens. Unlike CARs, TRuCs become a functional component complex. TRuC-T kill as potently second-generation CAR-T cells, but at significant lower cytokine release...
Abstract The chemokine receptor CXCR3 promotes the trafficking of activated T and NK cells in response to three ligands, CXCL9, CXCL10, CXCL11. Although these chemokines are produced CNS multiple sclerosis experimental autoimmune encephalomyelitis (EAE), their role pathogenesis autoimmunity is unresolved. We examined function signaling EAE using mice that were deficient for (CXCR3−/−). time onset peak disease severity similar CXCR3−/− wild-type (WT) animals; however, had more severe chronic...
Abstract Ag-specific tolerance is a highly desired therapy for immune-mediated diseases. Intravenous infusion of protein/peptide Ags linked to syngeneic splenic leukocytes with ethylene carbodiimide (Ag-coupled splenocytes [Ag-SP]) has been demonstrated be efficient method inducing peripheral, T cell treatment autoimmune disease. However, little understood about the mechanisms underlying this therapy. In study, we show that apoptotic Ag-SP accumulate in marginal zone, where their uptake by...
A major challenge for human allogeneic islet transplantation is the development of effective methods to induce donor-specific tolerance obviate need life-long immunosuppression that toxic insulin-producing beta cells and detrimental host. We developed an efficient therapy utilizes infusions ethylene carbodiimide (ECDI)-treated donor splenic antigen-presenting results in indefinite survival grafts absence immunosuppression. Furthermore, we show induction critically dependent on synergistic...
Polymeric nanoparticles (NPs) have demonstrated their potential to induce antigen (Ag)-specific immunological tolerance in multiple immune models and are at various stages of commercial development. Association Ag with NPs is typically achieved through surface coupling or encapsulation methods. However, these methods limitations that include high polydispersity, uncontrollable loading release, possible immunogenicity. Here, using antigenic peptides conjugated poly(lactide-co-glycolide), we...
The interferon (IFN)-stimulated genes (ISGs) ISG-49, ISG-54, and ISG-56 are highly responsive to viral infection, yet the regulation function of these in vivo unknown. We examined simultaneous ISGs brains mice during infection with either lymphocytic choriomeningitis virus (LCMV) or West Nile (WNV). Expression ISG-49 increased significantly LCMV being widespread localized predominantly common as well distinct neuronal populations. ISG-54 gene also but lower levels a more restricted...
Abstract IL-6 is crucial for the induction of many murine models autoimmunity including experimental autoimmune encephalomyelitis (EAE), an animal model multiple sclerosis. To establish role site-specific production in autoimmunity, we examined myelin oligodendrocyte glycoprotein immunization-induced EAE transgenic mice (GFAP-IL6) with restricted to cerebellum. Myelin glycoprotein-immunized (Mi-) GFAP-IL6 developed severe ataxia but no physical signs spinal cord involvement, which was sharp...
Significance Allergic diseases are characterized by inappropriate inflammatory responses to benign environmental antigens (Ags). Primary clinical approaches allergic disease consist of symptom control or administration soluble Ag skew the immune response alternate phenotypes induce tolerance. However, such carry a significant risk adverse events and require long treatment course achieve efficacy. In this paper, we describe use i.v.-administered nanoparticles as carriers whole-protein...
Infiltration of Ly6C(hi) monocytes from the blood is a hallmark viral encephalitis. In mice with lethal encephalitis caused by West Nile virus (WNV), an emerging neurotropic flavivirus, inhibition monocyte trafficking into brain anti-very late antigen (VLA)-4 integrin antibody blockade at time first weight loss and leukocyte influx resulted in long-term survival up to 60% infected mice, subsequent sterilizing immunity. This treatment had no effect on titers but appeared be due macrophage...
Abstract Seizures are a major complication of viral encephalitis. However, the mechanisms seizure‐associated neuronal dysfunction remain poorly understood. We report that intranasal inoculation with West Nile virus (WNV) (Sarafend) causes limbic seizures in C57BL/6 mice, but not interferon (IFN)‐γ‐deficient (IFN‐γ −/− ) mice. Both strains showed similar levels brain, as well concentrations cytokines, tumor necrosis factor and interleukin‐6, both which can alter excitability. Experiments...