A5064924657- Genetic factors in colorectal cancer
- Lung Cancer Treatments and Mutations
- Microtubule and mitosis dynamics
- Cancer Cells and Metastasis
- RNA modifications and cancer
- Lung Cancer Diagnosis and Treatment
- Cancer Treatment and Pharmacology
- Cancer Genomics and Diagnostics
- Cancer, Hypoxia, and Metabolism
- Cancer-related Molecular Pathways
- Cell Image Analysis Techniques
- Ubiquitin and proteasome pathways
- Skin and Cellular Biology Research
- Cell Adhesion Molecules Research
- Cellular Mechanics and Interactions
- HER2/EGFR in Cancer Research
- 14-3-3 protein interactions
- Phytochemicals and Medicinal Plants
- Metabolism, Diabetes, and Cancer
- Advanced Breast Cancer Therapies
- Plant Molecular Biology Research
- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- 3D Printing in Biomedical Research
- Architecture and Computational Design
Emory University
2016-2025
Medscape
2022-2024
Human Rights Watch
2024
Winship Cancer Institute
2007-2024
Piedmont Cancer Institute
2008-2024
Center for Scientific Integrity
2023
California College of the Arts
2018
Cancer Institute (WIA)
2007-2017
Yale University
2013
Palmetto Hematology Oncology
2013
We report the use of Tat peptide-conjugated quantum dots (Tat-QDs) to examine complex behavior nanoparticle probes in live cells, a topic that is considerable current interest developing advanced agents for molecular and cellular imaging. Dynamic confocal imaging studies indicate QDs are internalized by macropinocytosis, fluid-phase endocytosis process triggered Tat-QD binding negatively charged cell membranes. The Tat-QDs tethered inner vesicle surfaces trapped cytoplasmic organelles. QD...
Abstract Withaferin A (WFA) is purified from the plant Withania somnifera and inhibits vimentin cytoskeleton. Vimentin overexpression in cancer correlates with metastatic disease, induction of epithelial to mesenchymal transition reduced patient survival. As functions cell motility, we wanted test hypothesis that WFA metastasis by disrupting function. These data showed had weak cytotoxic apoptotic activity at concentrations less than or equal 500 nM, but retained potent anti‐invasive these...
Abstract Purpose: Vimentin is an epithelial-to-mesenchymal transition (EMT) biomarker and intermediate filament protein that functions during cell migration to maintain structure motility. Despite the abundance of clinical data linking vimentin poor patient outcome, it unclear if required for metastasis or a correlative biomarker. We developed novel genetically engineered mouse model (GEMM) probe in lung adenocarcinoma metastasis. Experimental Design: used LSL-KrasG12D/Lkb1fl/fl/Vim−/−...
Abstract As genomics advances reveal the cancer gene landscape, a daunting task is to understand how these genes contribute dysregulated oncogenic pathways. Integration of into networks offers opportunities protein–protein interactions (PPIs) with functional and therapeutic significance. Here, we report generation cancer-focused PPI network, termed OncoPPi, identification >260 cancer-associated PPIs not in other large-scale interactomes. hubs new regulatory mechanisms for like MYC , STK11...
Quantum dot bioconjugates can be used for multiplexed and quantitative detection of tumor biomarkers in cells tissues. This new technology should have significant impact on molecular pathology if validated with traditional techniques (such as western blotting, FISH, IHC), large-scale clinical studies. In addition, it could also become the first application quantum dots.
Arl2 and Arl3 are closely related members of the Arf family regulatory GTPases that arose from a common ancestor early in eukaryotic evolution yet retain extensive structural, biochemical, functional features. The presence centrosomes, mitotic spindles, midzones, midbodies, cilia all supportive roles microtubule-dependent processes. Knockdown by siRNA resulted changes cell morphology, increased acetylation alpha-tubulin, failure cytokinesis, number binucleated cells. We conclude binds...
Taxanes are powerful chemotherapy agents that target the microtubule cytoskeleton, leading to mitotic arrest and cell death; however, their clinical efficacy has been hampered due development of drug resistance. Therefore, other proteins involved in spindle assembly being examined as potential targets for anticancer therapy. The kinesin, Eg5 is critical proper assembly; such, inhibition leads making it a target. We wanted validate therapeutic determine if inhibitors retain activity...
Head and neck squamous cell carcinoma (HNSCC) is one of the most common types human cancer frequently metastasizes to LNs. Identifying metastasis-promoting factors immense clinical interest, as prognosis for patients with even a single unilateral LN metastasis extremely poor. Here, we report that p90 ribosomal S6 kinase 2 (RSK2) promotes HNSCC invasion metastasis. We determined RSK2 was overexpressed activated in highly invasive lines compared poorly lines. Expression also correlated...
Abstract Phenotypic heterogeneity is widely observed in cancer cell populations. Here, to probe this heterogeneity, we developed an image-guided genomics technique termed spatiotemporal genomic and cellular analysis (SaGA) that allows for precise selection amplification of living rare cells. SaGA was used on collectively invading 3D packs create purified leader follower lines. The cultures are phenotypically stable highly invasive contrast cultures, which show phenotypic plasticity over time...
Withaferin A (WA), a C5,C6-epoxy steroidal lactone derived from medicinal plant (Withania somnifera), inhibits growth of human breast cancer cells in vitro and vivo prevents mammary development transgenic mouse model. However, the mechanisms underlying anticancer effect WA are not fully understood. Herein, we report that tubulin is novel target WA-mediated arrest cells. The G2 mitotic resulting exposure MCF-7, SUM159, SK-BR-3 was associated with marked decrease protein levels β-tubulin....
// LaTonia Taliaferro-Smith 1 , Elaine Oberlick 1, 2 Tongrui Liu Tanisha McGlothen Tiffanie Alcaide Rachel Tobin Siobhan Donnelly 3 Commander Erik Kline Ganji Purnachandra Nagaraju Lauren Havel Adam Marcus Rita Nahta Ruth O’Regan 4 Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School Medicine, Atlanta, GA, 30322 USA Graduate Program in Biological Biomedical Sciences, Harvard School, Boston, MA, 02115 Pharmacology, Georgia Center for...
Phenotypic heterogeneity exists within collectively invading packs of tumor cells, suggesting that cellular subtypes cooperate to drive invasion and metastasis. Here, we take a chemical biology approach probe cell:cell cooperation the collective pack. These data reveal metabolic invasive chains, in which leader cells preferentially utilize mitochondrial respiration trailing follower rely on elevated glucose uptake. We define pyruvate dehydrogenase (PDH) dependency can be therapeutically...
The spindle plays a central role in chromosome segregation during mitosis and meiosis. In particular, various kinesins are thought to play crucial roles structure function both meiosis of fungi animals. A group putative has been previously identified Arabidopsis, called ATK1-ATK4 (previously known as KATA-KATD), but their vivo functions have not tested with genetic studies. We report here the isolation characterization mutant, atk1-1, which defective ATK1 gene. atk1-1 mutant was collection...
Diverse kinesin motor proteins are involved in spindle function; however, the mechanisms by which they targeted to specific sites within spindles not well understood. Here, we show that a fusion between yellow fluorescent protein (YFP) and minus-end-directed Kinesin-14 (C-terminal family) from Arabidopsis, ATK5, localizes mitotic midzones regions rich growing plus-ends phragmoplasts. Notably, Arabidopsis interphase cells, YFP::ATK5 microtubules with preferential enrichment at plus-ends;...
We have shown previously that withaferin A (WA), a bioactive component of the medicinal plant Withania somnifera, inhibits growth cultured and xenografted human breast cancer cells prevents development pulmonary metastasis incidence in transgenic mouse model. The present study was undertaken to determine if anticancer effect WA involved inhibition epithelial–mesenchymal transition (EMT). Experimental EMT induced by exposure MCF-10A tumor necrosis factor-α (TNF-α) transforming factor-β1...
Though clinicians can predict which patients are at risk for developing metastases, traditional therapies often prove ineffective and metastatic disease is the primary cause of cancer patient death; therefore, there a need to develop anti-metastatic that be administered over long durations specifically inhibit motility cells. Withania somnifera root extracts (WRE) have anti-proliferative activity active component, Withaferin A, inhibits pro-metastatic protein, vimentin. Vimentin an...
Complete removal of tumors by surgery is the most important prognostic factor for cancer patients with early stage cancers.The ability to identify invasive tumor edges primary tumor, locally invaded small lesions, and drug resistant residual following neoadjuvant therapy during should significantly reduce incidence local recurrence improve survival patients.In this study, we report that urokinase plasminogen activator (uPA) its receptor (uPAR) are ligand/cell surface target pair development...
Specialized leader cells use stable filopodia to create linear fibronectin tracks promote collective cancer invasion.
Abstract Farnesyl transferase (FT) inhibitors (FTI) are anticancer agents developed to target oncogenic Ras proteins by inhibiting farnesylation. FTIs potently synergize with paclitaxel and other microtubule-stabilizing drugs; however, the mechanistic basis underlying this synergistic interaction remains elusive. Here we show that FTI lonafarnib affects microtubule cytoskeleton resulting in bundle formation, increased stabilization acetylation, suppression of dynamics. Notably, treatment...
Abstract The tumor suppressor LKB1 is mutated in 30% of non–small cell lung cancer (NSCLC) tumors and lines proposed to be a key regulator epithelial polarity; however, how regulates polarity not known. experiments described herein show for the first time that dynamic, actin-associated protein rapidly polarizes leading edge motile cells. proves essential NSCLC polarity, because depletion results classic defects, such as aberrant Golgi positioning, reduced lamellipodia formation, morphology....
Abstract The compound 2-deoxyglucose (2-DG) enhances chemotherapy/radiotherapy in cell lines and animal models, prompting two phase I clinical trials with this cancer therapeutic. Although its mechanism of action has not been fully elucidated, it is hypothesized that the molecular basis 2-DG activity related to glycolysis inhibition. Here, we report induced Akt phosphorylation at Thr308 Ser473 as early 15 min post-treatment. These events required phosphatidylinositol-3-kinase but were...