A5066651585- Immune cells in cancer
- Phagocytosis and Immune Regulation
- Melanoma and MAPK Pathways
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Cell Adhesion Molecules Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Macrophage Migration Inhibitory Factor
- Adipokines, Inflammation, and Metabolic Diseases
- CAR-T cell therapy research
- interferon and immune responses
- Nuclear Receptors and Signaling
- Liver Disease Diagnosis and Treatment
- Adenosine and Purinergic Signaling
- Lipoproteins and Cardiovascular Health
- Inflammation biomarkers and pathways
- Redox biology and oxidative stress
- COVID-19 Clinical Research Studies
- Epigenetics and DNA Methylation
- Retinoids in leukemia and cellular processes
- Synthesis and Catalytic Reactions
- Autophagy in Disease and Therapy
Moffitt Cancer Center
2021-2025
University of Alabama at Birmingham
2015-2019
C-reactive protein (CRP) is the prototypical acute phase reactant, increasing in blood concentration rapidly and several-fold response to inflammation. Recent evidence indicates that CRP has an important physiological role even at low, baseline levels or absence of overt For example, we have shown human inhibits progression experimental autoimmune encephalomyelitis (EAE) transgenic mice by shifting CD4+ T cells away from TH1 towards TH2 subset. Notably, this action required inhibitory Fcγ...
Previously we established that human C-reactive protein (CRP) exacerbates mouse acute kidney injury and the effect was associated with heightened renal accumulation of myeloid derived cells suppressor functions (MDSC). Herein provide direct evidence CRP modulates development suppressive actions MDSCs in vitro. We demonstrate dose-dependently increases generation MDSC from wild type bone marrow progenitors enhances production intracellular reactive oxygen species (iROS). When added to...
<title>Abstract</title> Chimeric antigen receptor (CAR) T cell therapies have revolutionized B malignancy treatment, but subsets of patients with large lymphoma (LBCL) experience primary resistance or relapse after CAR treatment. To uncover tumor microenvironment (TME)-induced mechanisms, we examined patients’ intratumoral immune infiltrates and observed that elevated levels immunoregulatory macrophages in pre-infusion biopsies are correlated poor clinical responses. cell-produced...
Abstract Background: Activating NRAS mutations occur in 15-25% of melanomas; however, this subtype is highly aggressive and refractory to existing therapeutic approaches. Consequently, the identification novel molecular mechanisms critical clinical importance. Melanomas harbor hyperactive nitric oxide synthases (NOS) that strongly correlate with poor prognosis. Here, we investigated role nitrosylation, a oxide-induced posttranslational modification, regulating oncogenic MEK/ERK signaling...
Abstract Our study delves into the complex interplay between tumor microenvironment and immune cell regulation, with a particular focus on myeloid-derived suppressor cells (MDSCs). A key discovery of our research is accumulation bile acids (BAs) within tumor-infiltrating myeloid cells. BAs significantly enhance suppressive function MDSCs M2 macrophages via activation Farnesoid X Receptor (FXR).Using melanoma as primary model. We demonstrate that modulation MDSCs' can be achieved through...
Abstract Activating NRAS mutations occur in 15-25% of all melanomas. However, this subtype remains refractory to existing therapeutics, including immunotherapy and RAS inhibitors; therefore, identifying innovative treatment strategies is utmost importance. We investigated the role nitrosylation, a nitric oxide-induced post-translational modification, melanoma progression therapeutic resistance. Inhibiting nitrosylation sensitized NRAS-mutant melanomas targeted MEK inhibitors (MEKi), leading...
We recently demonstrated that human C-reactive protein (CRP), expressed hepatically in transgenic mice (CRPtg), improved the outcome of experimental autoimmune encephalomyelitis (EAE), a murine model multiple sclerosis (MS). The liver is primary site CRP synthesis humans and CRPtg but also by both at low levels CNS. To determine if CNS expression sufficient to impact EAE, we generated neuronal (nCRPtg) wherein driven neuron-specific Ca 2+ /calmodulin-dependent kinase II α (CaMKII ) gene...
Abstract Genome-wide association studies (GWAS) and functional genomic analyses have implicated several ITGAM (CD11b) single-nucleotide polymorphisms (SNPs) in the development of SLE other disorders. encodes α M chain β 2 integrin Mac-1, a receptor that plays important roles myeloid cell functions. The SNP rs1143679, which results an arginine to histidine change at amino acid position 77 CD11b protein, has been shown reduce binding ligands alter Mac-1-mediated cellular response vitro....
Abstract The tumor microenvironment incites sustained endoplasmic reticulum (ER) stress in infiltrating T and myeloid cells, which impairs their antitumor potential through intrinsic activation of PKR-like kinase (PERK). Nonetheless, the immunomodulatory role PERK cell compartment remains unknown. Using multiple melanoma models, we established that ablation (PERKKO) cancer cells culminates caspase-independent immunogenic death (ICD) response to ER stress. In vivo, PERKKO underwent ICD...