A5000925607- Melanoma and MAPK Pathways
- Receptor Mechanisms and Signaling
- Cancer Cells and Metastasis
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Protein Kinase Regulation and GTPase Signaling
- Neuropeptides and Animal Physiology
- Immune cells in cancer
- 3D Printing in Biomedical Research
- PI3K/AKT/mTOR signaling in cancer
- Immunotherapy and Immune Responses
- Peptidase Inhibition and Analysis
- Biochemical and Molecular Research
- Computational Drug Discovery Methods
- Monoclonal and Polyclonal Antibodies Research
- Hippo pathway signaling and YAP/TAZ
- Cancer Research and Treatments
- Ubiquitin and proteasome pathways
- Nanoplatforms for cancer theranostics
- PARP inhibition in cancer therapy
- Synthesis of Tetrazole Derivatives
- Mass Spectrometry Techniques and Applications
- Cardiac electrophysiology and arrhythmias
- Neuroblastoma Research and Treatments
- Carcinogens and Genotoxicity Assessment
Kiyatec (United States)
2018-2024
Michigan State University
2016-2021
Medical University of South Carolina
2009-2019
The renin-angiotensin and kallikrein-kinin systems are key regulators of vascular tone inflammation. Angiotensin II, the principal effector system, promotes vasoconstriction by activating angiotensin AT1 receptors. opposing effects system mediated bradykinin acting on B1 B2 engage in cross-talk at multiple levels, including formation AT1-B2 receptor heterodimers. In primary smooth muscle cells, we find that arrestin pathway-selective agonist, [Sar(1),Ile(4),Ile(8)]-AngII, but not neutral...
Melanoma is the most dangerous form of skin cancer with majority deaths arising from metastatic disease. Evidence implicates Rho-activated gene transcription in melanoma metastasis mediated by nuclear localization transcriptional coactivator, myocardin-related factor (MRTF). Here, we highlight a role for Rho and MRTF signaling its reversal pharmacologic inhibition using vitro vivo models human growth metastasis. Using two cellular melanoma, clearly show that one cell type, SK-Mel-147, highly...
HDL normally transports about 50–70% of plasma sphingosine 1-phosphate (S1P), and the S1P in reportedly mediates several HDL-associated biological effects signaling pathways. The receptor, SR-BI, as well cell surface receptors for (S1PRs) may be involved partially and/or completely these HDL-induced processes. Here we investigate nature HDL-stimulated interaction between S1PR1 using a protein-fragment complementation assay confocal microscopy. In both primary rat aortic vascular smooth...
Abstract We report the development of a method to analyze receptor and β-arrestin2 mobilization between Class A B GPCRs via time-resolved fluorescent microscopy coupled with semiautomated high-content multiparametric analysis. Using transiently expressed, tagged β2-adrenergic (β 2 -AR) or parathyroid hormone type 1 (PTH R), we quantified trafficking receptors along colocalization coexpressed β-arrestin2. This classification system allows for exclusion cells nonoptimal characteristics...
The Ras/MEK/ERK pathway has been the primary focus of targeted therapies in melanoma; it is aberrantly activated almost 80% human cutaneous melanomas (≈50% BRAFV600 mutations and ≈30% NRAS mutations). While drugs targeting MAPK have yielded success mutant melanoma patients, such ineffective patients with part due to their cytostatic effects resistance. Here, we demonstrate that increased Rho/MRTF-pathway activation correlates high intrinsic resistance MEK inhibitor, trametinib, a panel cell...
Our growing appreciation of the pluridimensionality G protein-coupled receptor (GPCR) signaling, combined with phenomenon orthosteric ligand "bias", has created possibility drugs that selectively modulate different aspects GPCR function for therapeutic benefit. When viewed from short-term perspective, e.g. changes in conformation, effector coupling or second messenger generation, biased ligands appear to activate a subset response profile produced by conventional agonist. Yet when examined...
Abstract Gliomas, a type of brain tumor originating from glial cells, comprise heterogenous group neoplasms. High-grade gliomas, in particular, present significant therapeutic challenges the clinic. Unlike other solid tumors, glioma microenvironment is heavily enriched with associated suppressor cells including myeloid-derived (MDSCs) and tumor-associated macrophages (TAMs), which can account for 30-40% cellular composition1. These pro-tumorigenic myeloid are thought to contribute resistance...
Abstract Biological therapies for the treatment of cancer are utilized same ultimate purpose as chemically derived drugs, to induce tumor cell death. However, differing mechanisms action often make evaluation biologic drug efficacy more complex, requiring support and/or recapitulation functional immune components. Biologics also have different limitations that can govern their such large size potentially impeding sufficient penetration target sites and in case live biotherapeutic products,...
While structurally distinct ligands can “bias” the efficiency with which G protein-coupled receptors (GPCRs) activate different downstream effectors, it is thought that events of a single effector are inseparable. We tested panel type 1 parathyroid hormone receptor (PTH1R) for their effects on two β-arrestin-mediated processes, desensitization and β-arrestin-dependent signaling. Unlike conventional agonists, caused while activating signaling, we found β-arrestin biased agonists did not...
Background Cancerous cells can utilize immune checkpoints to escape T-cell-mediated cytotoxicity. Agents that target PD-1, PD-L1 and CTLA4 are collectively deemed checkpoint inhibitors (ICIs), many have been approved for treatment of non-small cell lung cancer (NSCLC) melanoma. Unfortunately, patients do not respond these therapies often experience disease progression. Immunohistochemistry assays predict response ICIs inconsistent in their readouts with low expression levels ICIs....
<div>Abstract<p>Melanoma is the most dangerous form of skin cancer with majority deaths arising from metastatic disease. Evidence implicates Rho-activated gene transcription in melanoma metastasis mediated by nuclear localization transcriptional coactivator, myocardin-related factor (MRTF). Here, we highlight a role for Rho and MRTF signaling its reversal pharmacologic inhibition using <i>in vitro</i> vivo</i> models human growth metastasis. Using two cellular...
<div>Abstract<p>Melanoma is the most dangerous form of skin cancer with majority deaths arising from metastatic disease. Evidence implicates Rho-activated gene transcription in melanoma metastasis mediated by nuclear localization transcriptional coactivator, myocardin-related factor (MRTF). Here, we highlight a role for Rho and MRTF signaling its reversal pharmacologic inhibition using <i>in vitro</i> vivo</i> models human growth metastasis. Using two cellular...
<p>The Cancer Genome Atlas (TCGA) cutaneous melanoma dataset was stratified into quartiles based upon expression of indicated genes. Kaplan-Meier plots were generated from the highest (grey) and lowest (black) expressing quartiles. Survival curves analyzed with log-rank test a cutoff P < 0.05 as statistically significant.</p>
<p>To show that MRTF-A localization was dependent on F-actin dynamics, we stimulated SK-Mel-19 cells with 20% FBS to induce stress fiber formation which induced nuclear localization. We also treated SK-Mel-147 latrunculin B inhibits and relocated the cytosol.</p>
<p>The Cancer Genome Atlas (TCGA) cutaneous melanoma dataset was stratified into quartiles based upon expression of indicated genes. Kaplan-Meier plots were generated from the highest (grey) and lowest (black) expressing quartiles. Survival curves analyzed with log-rank test a cutoff P < 0.05 as statistically significant.</p>
<p>To show that MRTF-A localization was dependent on F-actin dynamics, we stimulated SK-Mel-19 cells with 20% FBS to induce stress fiber formation which induced nuclear localization. We also treated SK-Mel-147 latrunculin B inhibits and relocated the cytosol.</p>
<h3>Background</h3> Improved efficiency of pre-clinical drug development translation to clinical use ensures that new therapeutics are available patients faster. Co-development and biomarker tests, such as PD-1/PD-L1 targeting agents with PD-L1 expression, have been advantageous for patient stratification. Unfortunately, they poor proxies response.<sup>1</sup> Animal models genomics traditionally used aide in predicting success. However, the Modernization Act 2.0, vitro model has received...