A5070391155- Immune Cell Function and Interaction
- Cell death mechanisms and regulation
- T-cell and B-cell Immunology
- Phagocytosis and Immune Regulation
- Autophagy in Disease and Therapy
- Immunotherapy and Immune Responses
- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- Immune cells in cancer
- Melanoma and MAPK Pathways
- Signaling Pathways in Disease
- SARS-CoV-2 and COVID-19 Research
- CAR-T cell therapy research
- Animal Virus Infections Studies
- Multiple Sclerosis Research Studies
- Immune Response and Inflammation
- Cancer Mechanisms and Therapy
- Chronic Lymphocytic Leukemia Research
- Virus-based gene therapy research
- Toxoplasma gondii Research Studies
- Protein Kinase Regulation and GTPase Signaling
- Autoimmune and Inflammatory Disorders Research
- Ubiquitin and proteasome pathways
University of California, Irvine
2015-2024
Institute of Immunology
2019
Multiple Sclerosis Research Institute
2015
UC Irvine Health
2014
Glasgow Caledonian University
2012
Irvine University
2010
Cancer Research Institute
2003-2006
University of California, San Diego
1998-2004
University of California, Los Angeles
1994-1999
Institut thématique Génétique, génomique et bioinformatique
1997
Mice lacking the perforin gene were generated by using targeted disruption in embryonal stem cells. When infected with lymphocytic choriomeningitis virus (LCMV), perforin-less (-/-) mice showed clear signs of having mounted an immune response based on activation CD8 T cells but unable to LCMV infection. This failure eliminate was accompanied a generate spleen capable lysing LCMV-infected fibroblasts vitro. Spleen from -/- able lyse hematopoietic target after exposure phorbol 12-myristate...
To dissect therapeutic mechanisms of transplanted stem cells and develop exosome-based nanotherapeutics in treating autoimmune neurodegenerative diseases, we assessed the effect exosomes secreted from human mesenchymal (MSCs) multiple sclerosis using an experimental encephalomyelitis (EAE) mouse model. We found that intravenous administration produced by MSCs stimulated IFNγ (IFNγ-Exo) (i) reduced mean clinical score EAE mice compared to PBS control, (ii) demyelination, (iii) decreased...
Myeloid-derived suppressor cells (MDSCs) are innate immune that acquire the capacity to suppress adaptive responses during cancer. It remains elusive how MDSCs differ from their normal myeloid counterparts, which limits our ability specifically detect and therapeutically target Here, we sought determine molecular features of breast cancer-associated using widely studied mouse model based on mammary tumor virus (MMTV) promoter-driven expression polyomavirus middle T oncoprotein (MMTV-PyMT)....
Fas-associated death domain protein (FADD) and caspase-8 (casp8) are vital intermediaries in apoptotic signaling induced by tumor necrosis factor family ligands. Paradoxically, lymphocytes lacking FADD or casp8 fail to undergo normal clonal expansion following antigen receptor cross-linking succumb caspase-independent cell upon activation. Here we show that T cells activity subject hyperactive autophagic subvert a cellular survival mechanism into potent process. autophagy, enhanced mitogenic...
ABSTRACT Cytotoxic T cells secrete perforin to kill virus-infected cells. In this study we show that also plays a role in immune regulation. Perforin-deficient (perf −/−) mice chronically infected with lymphocytic choriomeningitis virus (LCMV) contained greater numbers of antiviral compared persistently +/+ mice. The enhanced expansion was seen both CD4 and CD8 cells, but the most striking difference LCMV-specific present perf −/− Persistent LCMV infection results deletion anergy...
Disruption of the blood-brain barrier (BBB) is a defining and early feature multiple sclerosis (MS) that directly damages central nervous system (CNS), promotes immune cell infiltration, influences clinical outcomes. There an urgent need for new therapies to protect restore BBB function, either by strengthening endothelial tight junctions or suppressing vesicular transcytosis. Although wingless integrated MMTV (Wnt)/β-catenin signaling plays essential role in formation maintenance healthy...
Caspase-8 (casp8) is required for extrinsic apoptosis, and mice deficient in casp8 fail to develop die utero while ultimately failing maintain the proliferation of T cells, B a host other cell types. Paradoxically, these failures are not caused by defect but presumed proliferative function this protease. Indeed, following mitogenic stimulation, cells lacking or its adaptor protein FADD (Fas-associated death domain protein) hyperautophagic morphology, programmed necrosis-like process termed...
Myonuclear apoptosis is an early event in the pathology of dystrophin-deficient muscular dystrophy mdx mouse. However, events that initiate are unknown, and whether elimination can ameliorate subsequent muscle wasting remains a major question. We have tested hypothesis cytotoxic T-lymphocytes myonuclear dystrophic muscle, examined perforin-mediated cytotoxicity plays role pathophysiology dystrophy. Mdx mice showed invasion by T cells helper at onset histologically detectable fiber pathology....
Abstract A complete genetic deficiency of the complement protein C1q results in SLE with nearly 100% penetrance humans, but molecular mechanisms responsible for this association have not yet been fully determined. opsonizes ACs enhanced ingestion by phagocytes, such as Mφ and iDCs, avoiding extracellular release inflammatory DAMPs upon loss membrane integrity dying cell. We previously showed that human monocyte-derived DCs ingesting autologous, C1q-bound LALs (C1q-polarized C1q-polarized...
Multiple sclerosis (MS) is a chronic, inflammatory autoimmune disease that affects the central nervous system (CNS) for which there no cure. In MS, encephalitogenic T cells infiltrate CNS causing demyelination and neuroinflammation; however, little known about role of regulatory (Tregs) in tissue repair. Transplantation neural stem progenitor (NSCs NPCs) promising therapeutic strategy to promote repair through cell replacement, although recent findings suggest transplanted NSCs also instruct...
Abstract The ability of bcl-2 in target cells to block cell-mediated cytotoxicity by allospecific CTL was tested. blocking effect variable. Because killing involves two different pathways, degranulation (perforin plus granzymes) and fas, we examined the on these pathways independently. Bcl-2 blocked apoptotic cell death induced either cytotoxic granule extracts or under conditions which fas pathway is blocked. On other hand, had no cell-killing Fas-specific mAb capable only via pathway....
Abstract The murine CTL hybridoma PMMI has been shown by the most sensitive techniques to be devoid of perforin. We thus used activated with PMA and ionomycin, investigate possible alternate lytic pathways in CTLs absence found that is equipped membrane TNF-alpha as a potential mechanism, but unlikely involved acute (4 h) reactions. On other hand, readily lyses target cells expressing gene for Fas Ag, does not lyse fas antisense DNA. generation fas-dependent lysis required protein synthesis...