A5032171890- Cancer Immunotherapy and Biomarkers
- NF-κB Signaling Pathways
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Lung Cancer Research Studies
- Peptidase Inhibition and Analysis
- Lung Cancer Treatments and Mutations
- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- Adenosine and Purinergic Signaling
- CAR-T cell therapy research
- Histone Deacetylase Inhibitors Research
- Virus-based gene therapy research
- Acute Myeloid Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer Mechanisms and Therapy
- Immune cells in cancer
- Synthesis and biological activity
- Cell death mechanisms and regulation
- T-cell and B-cell Immunology
- Cancer Research and Treatments
- MicroRNA in disease regulation
- Retinoids in leukemia and cellular processes
- RNA regulation and disease
Moffitt Cancer Center
2015-2024
University of South Florida
2007-2023
Florida College
2015
University of Tampa
2013
Systems, Applications & Products in Data Processing (Australia)
2007
United Arab Emirates University
2007
Columbia University
1997-2005
Salk Institute for Biological Studies
2003
Institut Pasteur
2003
Howard Hughes Medical Institute
2001
Studies on mice deficient in nuclear factor kappa B (NF-κB) subunits have shown that this transcription is important for lymphocyte responses to antigens and cytokine-inducible gene expression. In particular, the RelA (p65) subunit required induction of tumor necrosis factor-α (TNF-α)-dependent genes. Treatment RelA-deficient (RelA −/− ) mouse fibroblasts macrophages with TNF-α resulted a significant reduction viability, whereas +/+ cells were unaffected. Cytotoxicity both cell types was...
Nuclear factor kappa B (NF-kappa B) is a critical regulator of several genes which are involved in immune and inflammation responses. NF-kappa B, consisting 50-kDa protein (p50) 65-kDa (p65), bound to cytoplasmic retention called I B. Stimulation cells with variety inducers, including cytokines such as tumor necrosis interleukin-1, leads the activation translocation p50/65 into nucleus. However, vivo mechanism process remains unknown. Here, we provide first evidence that through...
NF-kappa B is an inducible transcription factor comprised of a 50-kD (p50) and 65-kD (p65) subunit. Induction activity, which critical event in many signal transduction pathways, involves release from cytoplasmic inhibitory protein, I kappa B, followed by translocation the active complex into nucleus. Earlier studies suggested that targets p65 subunit B. However, we demonstrate vitro vivo methods recently cloned B/MAD-3 interacts with both p50 subunits as well c-Rel. Furthermore,...
ABSTRACT The alpha/beta interferon (IFN-α/β) system represents one of the first lines defense against virus infections. As a result, most viruses encode IFN antagonistic factors which enhance viral replication in their hosts. We have previously shown that recombinant influenza A lacking NS1 gene (delNS1) only replicates efficiently IFN-α/β-deficient systems. Consistent with this observation, we found infection tissue culture cells delNS1 virus, but not wild-type induced high levels mRNA...
Transcription factors belonging to the NF-kappa B family are controlled by inhibitory I kappa proteins, mainly alpha and beta. Apparently normal at birth, alpha-/- mice exhibit severe runting, skin defects, extensive granulopoiesis postnatally, typically dying 8 days. Hematopoietic tissues from these display elevated levels of both nuclear mRNAs some, but not all, genes thought be regulated B. elevation results in phenotypic abnormalities because lacking p50 subunit show a dramatically...
Abstract Tissue damage induced by infection or injury can result in necrosis, a mode of cell death characterized induction an inflammatory response. In contrast, cells dying apoptosis do not induce inflammation. However, the reasons for underlying differences between these two modes inducing inflammation are known. Here we show that necrotic cells, but apoptotic activate NF-κB and expression genes involved tissue-repair responses, including neutrophil-specific chemokine KC...
Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder associated with dystrophin deficiency that results in chronic inflammation and severe skeletal muscle degeneration. In DMD mouse models patients, we find IkappaB kinase/NF-kappaB (IKK/NF-kappaB) signaling persistently elevated immune cells regenerative fibers. Ablation of 1 allele the p65 subunit NF-kappaB was sufficient to improve pathology mdx mice, model DMD. addition, conditional deletion IKKbeta mice elucidated functions...
A number of pathogenic and proinflammatory stimuli, the transforming growth factor-β (TGF-β) exert opposing activities in cellular immune responses. Here we show that RelA subunit nuclear factor κB (NF-κB/RelA) is necessary for inhibition TGF-β-induced phosphorylation, translocation, DNA binding SMAD signaling complexes by tumor necrosis factor-α (TNF-α). The antagonism mediated through up-regulation Smad7 synthesis induction stable associations between ligand-activated TGF-β receptors...
Abstract Myeloid-derived suppressor cells (MDSC) play an important role in tumor escape by suppressing T-cell responses. MDSC represent a group of myeloid lineage at different stages differentiation. Increased arginase activity and production reactive oxygen species (ROS) are among the main functional characteristics these cells. Recent studies have shown that all-trans retinoic acid (ATRA) had potent eliminating cancer patients tumor-bearing mice. ATRA differentiates into mature However,...
Ras proteins function in stimulating cell proliferation and differentiation through the activation of Raf-dependent Raf-independent signal transduction pathways subsequent specific transcription factors. The factor NF-κB has been widely studied as a regulator genes involved immune inflammatory responses. A variety stimuli activate induced phosphorylation degradation inhibitor IκB followed by nuclear translocation NF-κB. We show here that oncogenic forms Ha-Ras NF-κB, not translocation, but...
A significant limitation of checkpoint blockade immunotherapy is the relatively low response rate (e.g., ∼20% with PD-1 in lung cancer). In this study, we tested whether strategies that increase T-cell infiltration to tumors can be efficacious enhancing response.We performed an unbiased screen identify FDA-approved oncology agents ability enhance chemokine expression goal identifying capable augmenting response. Identified were multiple tumor models as single and combination blockade....
The ubiquitous transcription factor NF-kappa B is regulated by its cytoplasmic inhibitor I kappa B. A variety of cellular stimuli cause the dissociation from B, allowing to translocate nucleus and regulate gene expression. Although activation in vivo associated with phosphorylation degradation alpha, it has remained unclear how each these events contributes this process. Recently, studies utilizing protease inhibitors have suggested that proteolysis alpha a necessary event We demonstrate...
NF-kappaB binding sites are present in the promoter regions of many acute phase and inflammatory response genes, suggesting that plays an important role initiation innate immune responses. However, targeted mutations various family members have yet to identify responsible for this critical role. RelA-deficient mice die on embryonic day 15 from TNF-alpha-induced liver degeneration. To investigate importance RelA immunity, we genetically suppressed lethality by breeding deficiency onto a TNFR...
Transcription factors of the nuclear factor (NF)-κB/Rel family translocate into nucleus upon degradation IκBs. Postinduction repression NF-κB activity depends on NF-κB–regulated resynthesis IκBα, which dissociates from DNA and exports it to cytosol. We found that after activation, p65/RelA is degraded by proteasome in a binding–dependent manner. If blocked, not promptly removed some target genes spite IκBα sustained transcription occurs. These results indicate proteasomal does merely...
Nuclear factor kappa B (NF-kappa B) is a critical regulator of several genes which are involved in immune and inflammation responses. NF-kappa B, consisting 50-kDa protein (p50) 65-kDa (p65), bound to cytoplasmic retention called I B. Stimulation cells with variety inducers, including cytokines such as tumor necrosis interleukin-1, leads the activation translocation p50/65 into nucleus. However, vivo mechanism process remains unknown. Here, we provide first evidence that through...
The Th17 cells use the retinoid-related orphan receptor-γ (Rorg or Rorc) to specify their differentiation and lineage-specific function. However, how Rorg is switched on during unknown. We report here that c-Rel RelA/p65 transcription factors drive by binding activating two distinct promoters control RORγT RORγ expression, respectively. Similar RORγT, selectively expressed in effective specifying phenotype. T deficient RelA are significantly compromised differentiation, c-Rel–deficient mice...