A5019929678- Immune Cell Function and Interaction
- Stress Responses and Cortisol
- Tryptophan and brain disorders
- Pancreatic function and diabetes
- T-cell and B-cell Immunology
- Chemokine receptors and signaling
- Immunotherapy and Immune Responses
- Diabetes and associated disorders
- CAR-T cell therapy research
- Retinal and Macular Surgery
- RNA Research and Splicing
- Gut microbiota and health
- interferon and immune responses
- Intraocular Surgery and Lenses
- Influenza Virus Research Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Corneal Surgery and Treatments
- Epigenetics and DNA Methylation
- Polyamine Metabolism and Applications
- Mental Health Research Topics
Roswell Park Comprehensive Cancer Center
2018-2024
Abstract Metabolic flexibility has emerged as a critical determinant of CD8+ T-cell antitumor activity, yet the mechanisms driving metabolic T cells have not been determined. In this study, we investigated influence nuclear cap-binding complex (CBC) adaptor protein ARS2 on mature cells. doing so, discovered novel signaling axis that endows activated with glucose catabolism. upregulation driven by CD28 reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third...
Polyamine inhibition for cancer therapy is, conceptually, an attractive approach but has yet to meet success in the clinical setting. The aryl hydrocarbon receptor (AHR) is central transcriptional regulator of xenobiotic response. Our study revealed that AHR also positively regulates intracellular polyamine production via direct activation 2 genes, ODC1 and AZIN1, which are involved biosynthesis control, respectively. In patients with multiple myeloma (MM), levels were inversely correlated...
Durable humoral immunity against epidemic infectious disease requires the survival of long-lived plasma cells (LLPCs). LLPC longevity is dependent on metabolic programs distinct from short-lived (SLPCs); however, mechanistic basis for this difference unclear. We have previously shown that CD28, prototypic T cell costimulatory receptor, expressed both LLPCs and SLPCs but essential only survival. Here we show CD28 transduces pro-survival signaling specifically in through differential SLP76...
Abstract CD8 T cell activation prompts extensive transcriptome remodeling underlying effector differentiation and function. Regulation of composition by the mitogen-inducible nuclear cap-binding complex (CBC) adaptor protein ARS2 has critical type-specific consequences, including thymic survival. Here we show that was upregulated CD28 during peripheral cells, essential for anti-tumor immunity, facilitated activation-induced alternative splicing. The novel splicing function mediated at least...
Abstract Durable humoral immunity depends upon bone marrow resident long-lived plasma cell (LLPC) survival. We have shown that CD28, the canonical T-cell costimulatory molecule, is required for LLPC survival; however, mechanistic basis this unclear. published of two binding motifs in CD28 cytoplasmic tail, only Grb2/Vav moiety, and not direct PI3k motif, supports CD28-mediated known to induce glycolysis T-cells. In contrast, activation both LLPCs human PCs induces glucose metabolism through...
Abstract Long lived plasma cells (LLPCs) are essential for sustained antibody responses and protective humoral immunity. How these maintain longevity a durable response is largely dependent on the complex nature of bone marrow microenvironment in which reside, pro survival factors produced this niche. Previous work our lab has shown that CD28 required LLPC survival, we know back signaling to CD80/86 induces IDO production from dendritic (DCs) within microenvironment. classically known...
Abstract Long lived plasma cells (LLPC) are a key component of protective humoral immunity. The ability these to maintain longevity and durable antibody response is largely dependent on the complex nature bone marrow (BM) microenvironment in which reside. Our lab has demonstrated that co-stimulatory receptor, CD28, essential for survival function LLPC. Furthermore, when CD28 LLPC ligates with CD80/CD86 expressed DC, it induces upregulation enzyme indoleamine 2,3-dioxygenase (IDO),...
Durable humoral immunity is essential for protection against many pathogens. The human health impact of this reflected in the estimate that current immunizations prevent 2-3 million deaths worldwide annually. This long-term protective primarily dependent on continual production neutralizing antibodies by distinct subset long-lived plasma cells (LLPC). LLPC are not intrinsically long lived, but rather critically interactions with stromal niche survival. However, it remains unclear which and...
Abstract Protective antibodies against diseases such as measles and polio primarily come from bone marrow (BM) resident long lived plasma cells (LLPC) are a key component of durable humoral immunity. As LLPC not innately major question remains about how these maintain survival. Our lab has previously demonstrated that the T cell receptor, CD28, is essential for survival function LLPC. Here we further demonstrate when CD28 on ligates with CD80/CD86 DC, it induces upregulation activation...