A5043054491- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cytokine Signaling Pathways and Interactions
- NF-κB Signaling Pathways
- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- PI3K/AKT/mTOR signaling in cancer
- PARP inhibition in cancer therapy
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Toxin Mechanisms and Immunotoxins
- Cancer, Hypoxia, and Metabolism
- Chemokine receptors and signaling
- IL-33, ST2, and ILC Pathways
- interferon and immune responses
- Diabetes and associated disorders
- Asthma and respiratory diseases
- CAR-T cell therapy research
- Mast cells and histamine
- Reproductive System and Pregnancy
- Cardiac tumors and thrombi
- Vascular Tumors and Angiosarcomas
- Monoclonal and Polyclonal Antibodies Research
- Cell Adhesion Molecules Research
- Mass Spectrometry Techniques and Applications
Vanderbilt University
2016-2025
Vanderbilt University Medical Center
2008-2025
University of Debrecen
2024
Vanderbilt-Ingram Cancer Center
2020
Bipar
1999-2020
Delft University of Technology
2019-2020
Breast Cancer Research Foundation
2020
Biology of Infection
2020
VA Tennessee Valley Healthcare System
2010-2018
Imperial College London
2013
Cytokines are inflammatory mediators important in responding to pathogens and other foreign challenges. Interleukin-4 (IL-4) IL-13 two cytokines produced by T helper type 2 cells, mast basophils. In addition their physiological roles, these also implicated pathological conditions such as asthma allergy. IL-4 can stimulate receptors, I II, whereas signaling is mediated only the II receptor (see STKE Connections Maps). These activate Janus kinase/signal transducer activator of transcription...
Abstract Despite the global impact of macrophage activation in vascular disease, underlying mechanisms remain obscure. Here we show, with proteomic analysis cell lines treated either IFNγ or IL-4, that PARP9 and PARP14 regulate activation. In primary macrophages, have opposing roles silencing induces pro-inflammatory genes STAT1 phosphorylation M(IFNγ) cells, whereas it suppresses anti-inflammatory gene expression STAT6 M(IL-4) cells. ADP-ribosylation STAT1, which is suppressed by PARP9....
Rapidly proliferating tumor and immune cells need metabolic programs that support energy biomass production. The amino acid glutamine is consumed by effector T glutamine-addicted triple-negative breast cancer (TNBC) cells, suggesting a competition for may exist within the microenvironment, potentially serving as therapeutic intervention strategy. Here, we report there an inverse correlation between genes markers of cell-mediated cytotoxicity in human basal-like (BLBC) patient data sets, with...
Abstract The majority of the genome is noncoding and was thought to be nonfunctional. However, it now appreciated that transcriptional control protein coding genes resides within these regions. Thousands encoding long intergenic RNAs (lincRNAs) have been recently identified throughout genome, which positively or negatively regulate transcription neighboring target genes. Both TMEVPG1 its mouse ortholog encode lincRNAs are positioned near IFN-γ gene (IFNG). In this study, we show both human...
Several mutants derived from transformed human B cell lines are defective in expressing major histocompatibility complex (MHC) class II genes. The failure to express a gene at least one such mutant line has been mapped the MHC X box, conserved transcriptional element promoter region. A complementary DNA encoding DNA-binding protein (human box binding protein, hXBP-1) whose target is DR alpha and 3' flanking region now cloned. This encoded with structural similarities c-jun proto-oncogene...
Members of the nuclear factor (NF)-κB/Rel family transcription factors are induced during thymic selection and in mature T lymphocytes after ligation cell antigen receptor (TCR). Despite these findings, disruption individual NF-κB/Rel genes has revealed no intrinsic defect development cells, perhaps reflecting functional redundancy. To circumvent this possibility, lineage was targeted to express a trans-dominant form IκBα that constitutively represses activity multiple proteins. Transgenic...
Prostaglandin E2 (PGE2), a major COX metabolite, plays important roles in several facets of tumor biology. We characterized the contribution PGE2 EP2 receptor to cancer-associated immune deficiency using EP2–/– mice. mice exhibited significantly attenuated growth and longer survival times when challenged with MC26 or Lewis lung carcinoma cell lines as compared their wild-type littermates. While no differences T function were observed, suppressed differentiation DCs from bone marrow...
kb, kilobases; FT, first trimester; ds cDNA, double-stranded
Probes derived from clones bearing cDNAs corresponding to the alpha subunit of human chorionic gonadotropin (hCG) and placental lactogen (hPL) were used localize their respective mRNAs cytologically in sections first trimester term placenta. hPL mRNA was exclusively localized syncytial layer, hCG found layer also some differentiating cytotrophoblasts. Hybridization specific because no signal observed when labeled pBR322 hybridized or probes tonsils. In addition, RNA interstitial cells did...
Abstract Semi-invariant NKT cells are thymus-derived innate-like lymphocytes that modulate microbial and tumor immunity as well autoimmune diseases. These immunoregulatory properties of acquired during their development. Much has been learned regarding the molecular cellular cues promote cell development, yet how these maintained in thymus periphery they acquire functional competence incompletely understood. We found IL-15 induced several Bcl-2 family survival factors thymic splenic vitro....
Significance The precise regulation of antibody responses is central to the efficacy vaccines and our handling microbes infections. Antibody quality enhanced in germinal center reactions, this microstructure tissue has cope with limited oxygen. This work shows that a pair hypoxia-inducible factor (HIF) proteins, gene regulators respond low oxygen but also are induced by T cell activation, must be expressed helper cells order for immunization yield good response. evidence favors...
Notch plays critical roles in both cell fate decisions and tumorigenesis. receptor engagement initiates signaling cascades that include a phosphatidylinositol 3-kinase/target of rapamycin (TOR) pathway. Mammalian TOR (mTOR) participates two distinct biochemical complexes, mTORC1 mTORC2, the relationship between mTORC2 physiological outcomes dependent on is unknown. In this study, we report contributions to thymic T-cell acute lymphoblastic leukemia (T-ALL) driven by Notch. Conditional...
While 30%–70% of RSV-infected infants develop bronchiolitis, 2% require hospitalization. It is not clear why disease severity differs among healthy, full-term infants; however, virus titers, inflammation, and Th2 bias are proposed explanations. TLR4 associated with these phenotypes, the role this receptor in respiratory syncytial (RSV) pathogenesis controversial. Here, we evaluated interaction between environmental factors RSV defined immune mediators severe illness. Two independent...
Abstract Purpose: Metastatic breast cancers continue to elude current therapeutic strategies, including those utilizing PI3K inhibitors. Given the prominent role of PI3Kα,β in tumor growth and PI3Kγ,δ immune cell function, we sought determine whether inhibition altered antitumor immunity. Experimental Design: The effect on growth, metastasis, response was characterized mouse models orthotopic implants 4T1 or PyMT mammary tumors into syngeneic PI3Kγ-null mice, patient-derived cancer...
Abstract The enzymes of the poly-ADP-ribose polymerase (PARP) superfamily control many relevant cellular processes, but a precise understanding their activities in different physiological or disease contexts is largely incomplete. We found that transcription several Parp genes was dynamically regulated upon murine macrophage activation by endotoxin. PARP14 strongly induced inflammatory stimuli and translocated into nucleus stimulated cells. Quantitative mass spectrometry analysis showed...
Abstract T cell function is a critical determinant of immune responses as well susceptibility to allergic diseases. Activated cells can differentiate into effectors whose cytokine profile limited type 1 (IFN-γ-dominant) or 2 (IL-4-, IL-5-dominant) patterns. To investigate mechanisms that connect extracellular stimuli with the regulation effector function, we have measured transgenic mice NF-κB/Rel signaling pathway inhibited in cells. Surprisingly, these developed cell-dependent (IgE and...
Two recombinant phage clones bearing sequences corresponding to the 8 subunit of human chorionic gonadotropin (hCG@) were isolated from a genomic library.The / 3 mapped by blot hybridization restriction digests these DNAs and nonoverlapping inserts subcloned in pBR322 sequenced.The nucleotide-sequencing data show that hCGB is encoded at least three nonallelic genes.Moreover, based on analyses placental DNA, genes may be linked single cluster with four other hCGB-like genes.The sequenced all...
Treatment of splenic B lymphocytes and certain B-lineage cell lines with the mitogen lipopolysaccharide (LPS) lymphokine interleukin-4 (IL-4) induces expression germ line immunoglobulin C epsilon transcripts class switching to gene. We show that LPS-plus-IL-4 induction (termed I transcripts) occurs at transcriptional level in an Abelson murine leukemia virus-transformed pre-B-cell line. A 1.1-kb region DNA surrounding promoter endows inducible transcription a heterologous reporter gene...