A5056911226- Cell death mechanisms and regulation
- Ubiquitin and proteasome pathways
- Protein Tyrosine Phosphatases
- Cancer, Lipids, and Metabolism
- Ferroptosis and cancer prognosis
- Cytokine Signaling Pathways and Interactions
- Lung Cancer Research Studies
- RNA Interference and Gene Delivery
- Cancer-related Molecular Pathways
- interferon and immune responses
- Lung Cancer Treatments and Mutations
- Cancer therapeutics and mechanisms
- Peptidase Inhibition and Analysis
- RNA modifications and cancer
- NF-κB Signaling Pathways
- Cancer Research and Treatments
- Telomeres, Telomerase, and Senescence
- Phagocytosis and Immune Regulation
- Immune Cell Function and Interaction
- Cancer, Hypoxia, and Metabolism
- Protein Degradation and Inhibitors
- Cancer Mechanisms and Therapy
- Ultrasound and Cavitation Phenomena
- Galectins and Cancer Biology
- Epigenetics and DNA Methylation
Virginia Commonwealth University
2015-2025
Philips (United States)
2017-2023
VCU Massey Comprehensive Cancer Center
2015-2022
Virginia Cancer Institute
2015-2022
AbbVie (United States)
2021
Children's Hospital of Richmond at VCU
2017
Meisei University
1998-2015
Nippon Medical School
2014
The University of Kitakyushu
2009-2011
Case Western Reserve University
2010
Production of nitric oxide (NO) by macrophages is important for the killing intracellular infectious agents. Interferon (IFN)- γ and lipopolysaccharide stimulate NO production transcriptionally up-regulating inducible synthase (iNOS). Macrophages from mice with a targeted disruption IFN regulatory factor-1 (IRF-1) gene (IRF-1 -/- mice) produced little or no synthesized barely detectable iNOS messenger RNA in response to stimulation. Two adjacent IRF-1 elements were identified promoter....
Interferon regulatory factor-1 (IRF-1), a transcriptional activator, and IRF-2, its antagonistic repressor, have been identified as regulators of type I interferon interferon-inducible genes. The IRF-1 gene is itself hence may be one the target genes critical for action. When IRF-2 was overexpressed in NIH 3T3 cells, cells became transformed displayed enhanced tumorigenicity nude mice. This phenotype reversed by concomitant overexpression gene. Thus, restrained cell growth depends on balance...
One of the most frequent cytogenetic abnormalities in human leukemia and myelodysplasia is an interstitial deletion within chromosome 5q. A tumor suppressor gene has been hypothesized to lie 5q31, smallest commonly deleted region. IRF-1 , a whose product manifests anti-oncogenic activity, was mapped 5q31.1. lies between IL-5 CDC25C centromeric IL-3 GM-CSF . Among these genes, only consistently at one or both alleles 13 cases with aberrations 5q31. Inactivating rearrangements allele,...
Abstract The Bcl-2 antagonist ABT-737 targets Bcl-2/Bcl-xL but not Mcl-1, which may confer resistance to this novel agent. Here, we show that Mcl-1 down-regulation by the cyclin-dependent kinase (CDK) inhibitor roscovitine or Mcl-1-shRNA dramatically increases lethality in human leukemia cells. induces Bax conformational change fails activate Bak trigger translocation. Coadministration of and untethers from Bcl-xL, respectively, triggering activation Studies employing and/or knockout mouse...
The mechanisms underlying interferon (IFN)-induced antiviral states are not well understood. Interferon regulatory factor-1 (IRF-1) is an IFN-inducible transcriptional activator, whereas IRF-2 suppresses IRF-1 action. inhibition of encephalomyocarditis virus (EMCV) replication by IFN-α and especially IFN-γ was impaired in cells from mice with a null mutation the gene (IRF-1 -/- mice). were less resistant than normal to EMCV infection, as revealed accelerated mortality larger titer target...
BAD interacts with anti-apoptotic molecules BCL-2 and BCL-X<sub>L</sub> promotes apoptosis. is phosphorylated on serine residues in response to a survival factor, interleukin-3. Phosphorylated cannot bind or at membrane sites found the cytosol bound 14-3-3. We report here that deletion mapping site-directed mutagenesis identified BH3 domain within proved necessary for both its heterodimerization death agonist activity. Substitution of conserved Leu<sup>151</sup> Ala amphipathic α-helix...
Interferon regulatory factor 1 (IRF-1) and IRF-2 are structurally similar DNA-binding factors which were originally identified as regulators of the type I interferon (IFN) system; former functions a transcriptional activator, latter represses IRF-1 function by competing for same cis elements. More recent studies have revealed new roles two in regulation cell growth; manifest antioncogenic oncogenic activities, respectively. In this study, we determined structures chromosomal locations human...
The “BH3-only” proapoptotic BCL-2 family members initiate the intrinsic apoptotic pathway. A small interfering RNA knockdown of BIM confirms this BH3-only member is important for cytokine-mediated homeostasis hematopoietic cells. We show here that phosphorylation status controls its activity. IL-3, a survival factor, induces extracellular signal-regulated kinase/mitogen-activated protein kinase-mediated on three serine sites (S55, S65, and S100). After IL-3 withdrawal, only nonphosphorylated...
The proapoptotic activity of the “BH3-only” molecule BAD can be differentially regulated by survival factor signaling. Bad -deficient mice lacking both long and short proteins proved viable, most cell types appeared to develop normally. did not exclusively account for death after withdrawal factors, but it was an intermediate epidermal growth factor- or insulin-like I-countered apoptosis, consistent with a “sensitizing” BH3-only molecule. Lymphocytes developed normally no premalignant...
Background: Interferons (IFNs) are a class of cytokines which confer cellular resistance against viral infections. Type I (IFN‐α and ‐β) type II (IFN‐γ) IFNs utilize distinct receptors, the stimulation results in induction downstream target genes. These genes usually contain within their promoter region an IFN responsive element, termed ISRE (IFN stimulated response element) binds heterotrimeric transcription factor, ISGF3 (IFN‐stimulated gene factor 3) consisting p48 (ISGF3 γ), Stat1...
Anthocyanins are a group of naturally occurring phenolic compounds widely available in fruits and vegetables human diets. They have broad biological activities including anti-mutagenesis anticarcinogenesis, which generally attributed to their antioxidant activities. We studied the effects mechanisms most common type anthocyanins, cyanidin-3-rutinoside, several leukemia lymphoma cell lines. found that cyanidin-3-rutinoside extracted purified from black raspberry cultivar Jewel induced...
B cell homeostasis is maintained by a balance between the continual generation of new cells and their elimination. Here we show proapoptotic BCL-2 family members BAX BAK are essential for regulating number at both immature mature developmental stages. critical mediators death induced multiple stimuli. In addition, BAX- BAK-deficient display defective cycle progression to receptor crosslinking lipopolysaccharide, but not CpG-DNA. Furthermore, inducible deletion Bax Bak in adult mice results...
Tumor cells undergo senescence in response to both conventional and targeted cancer therapies. The induction of therapy can contribute unfavorable patient outcomes, potentially including disease relapse. This possibiliy is supported by our findings that tumor induced into doxorubicin or etoposide give rise viable tumors vivo. We further demonstrate sensitivity these senescent the senolytic ABT-263 (navitoclax), therefore providing a "two-hit" approach eliminate persist after exposure...
Fewer than half of children with high-risk neuroblastoma survive. Many these tumors harbor high-level amplification MYCN, which correlates poor disease outcome. Using data from our large drug screen we predicted, and subsequently demonstrated, that MYCN-amplified neuroblastomas are sensitive to the BCL-2 inhibitor ABT-199. This sensitivity occurs in part through low anti-apoptotic BCL-xL expression, high pro-apoptotic NOXA paradoxical, MYCN-driven upregulation NOXA. Screening for enhancers...
Significance Small-cell lung cancer (SCLC) is an aggressive carcinoma with few effective treatment options beyond first-line chemotherapy. BH3 mimetics, such as ABT-263, promote apoptosis in SCLC cell lines, but early phase clinical trials demonstrated no significant benefit. Here, we examine the sensitivity of a large panel including SCLC, to ABT-263 and find that high Bcl2-interacting mediator death (BIM) low myeloid leukemia 1 (MCL-1) expression together predict sensitivity. cells...
Abstract Purpose: Small-cell lung cancer (SCLC) is an often-fatal neuroendocrine carcinoma usually presenting as extensive disease, carrying a 3% 5-year survival. Despite notable advances in SCLC genomics, new therapies remain elusive, largely due to lack of druggable targets. Experimental Design: We used high-throughput drug screen identify venetoclax-sensitive subpopulation and validated the findings with multiple patient-derived xenografts SCLC. Results: Our consisting very large...
Previously, we discovered that FOSL1 facilitates the metastasis of head and neck squamous cell carcinoma (HNSCC) cancer stem cells in a spontaneous mouse model. However, molecular mechanisms remained unclear. Here, demonstrated serves as dominant activating protein 1 (AP1) family member is significantly upregulated HNSCC tumor tissues correlated with HNSCC. Mechanistically, exerts its function promoting tumorigenicity predominantly via selective association Mediators to establish...
The sensitivity to ABT-737, a prototype BH3 mimetic drug, varies in broad range small cell lung cancer (SCLC) cells. We have previously shown that the expression of Noxa, BH3-only pro-apoptotic BCL-2 family protein, is critical determinant ABT-737 sensitivity. show here Noxa regulates localization and stability MCL-1, an anti-apoptotic member, which results modulating Mutations within domain, carboxyl terminus mitochondrial targeting or ubiquitinated lysines not only change itself but also...