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20 results on '"Ward, Toby M."'

1. Hydrogel Pore‐Size Modulation for Enhanced Single‐Cell Western Blotting

Author

Duncombe, Todd A, Kang, Chi-Chih, Maity, Santanu, Ward, Toby M, Pegram, Mark D, Murthy, Niren, and Herr, Amy E

Subjects
Engineering, Biomedical Engineering, Cancer, Bioengineering, Blotting, Western, Breast Neoplasms, Cell Line, Tumor, Electrophoresis, Polyacrylamide Gel, Extracellular Signal-Regulated MAP Kinases, Green Fluorescent Proteins, Humans, Hydrogels, Light, Nucleocytoplasmic Transport Proteins, Porosity, Receptor, ErbB-2, Single-Cell Analysis, TOR Serine-Threonine Kinases, Receptor, erbB-2, cancer therapies, gradient gels, grayscale masks, hydrogel pore expansion, western blots, Physical Sciences, Chemical Sciences, Nanoscience & Nanotechnology, Chemical sciences, Physical sciences
Abstract

Pore-gradient microgel arrays enable thousands of parallel high-resolution single-cell protein electrophoresis separations for targets accross a wide molecular mass (25-289 kDa), yet within 1 mm separation distances. Dual crosslinked hydrogels facilitate gel-pore expansion after electrophoresis for efficient and uniform immunoprobing. The photopatterned, light-activated, and acid-expandable hydrogel underpins single-cell protein analysis, here for oncoprotein-related signaling in human breast biopsy.

Published
2016

11. Rescue of tropomyosin deficiency in Drosophila and human cancer cells by synaptopodin reveals a role of tropomyosin α in RhoA stabilization

Author

Wong, Jenny S, Iorns, Elizabeth, Rheault, Michelle N, Ward, Toby M, Rashmi, Priyanka, Weber, Ursula, Lippman, Marc E, Faul, Christian, Mlodzik, Marek, and Mundel, Peter

Subjects
Animals, Genetically Modified, Mice, Cell Line, Tumor, Neoplasms, education, Microfilament Proteins, NIH 3T3 Cells, Animals, Humans, macromolecular substances, Tropomyosin, rhoA GTP-Binding Protein, Article
Abstract

Tropomyosins are widespread actin-binding proteins that influence numerous cellular functions including actin dynamics, cell migration, tumour suppression, and Drosophila oocyte development. Synaptopodin is another actin-binding protein with a more restricted expression pattern in highly dynamic cell compartments such as kidney podocyte foot processes, where it promotes RhoA signalling by blocking the Smurf1-mediated ubiquitination of RhoA. Here, we show that synaptopodin has a shorter half-life but shares functional properties with the highly stable tropomyosin. Transgenic expression of synaptopodin restores oskar mRNA localization in Drosophila oocytes mutant for TmII, thereby rescuing germline differentiation and fertility. Synaptopodin restores stress fibres in tropomyosin-deficient human MDA-MB 231 breast cancer cells and TPMα-depleted fibroblasts. Gene silencing of TPMα but not TPMβ causes loss of stress fibres by promoting Smurf1-mediated ubiquitination and proteasomal degradation of RhoA. Functionally, overexpression of synaptopodin or RhoA(K6,7R) significantly reduces MDA-MB 231 cell migration. Our findings elucidate RhoA stabilization by structurally unrelated actin-binding proteins as a conserved mechanism for regulation of stress fibre dynamics and cell motility in a cell type-specific fashion.

Published
2011

16. Abstract 1211: Novel detection and characterization of truncated ERBB2 demonstrates potent oncogenicity of the p110 isoform in human mammary epithelial cells

Author

Ward, Toby M., primary, Iorns, Elizabeth, additional, Liu, Xinjun, additional, Singh, Sharat, additional, Kim, Phillip, additional, Jegg, Anna, additional, Dean, Sonja, additional, Gallas, Michelle, additional, Villasboas-Bisneto, Jose, additional, Lippman, Marc, additional, Landgraf, Ralf, additional, and Pegram, Mark, additional

Published
2011
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17. Abstract 4979: Whole genome in vivo RNA interference screening identifies the leukemia inhibitory factor receptor as a novel breast tumor suppressor

Author

Iorns, Elizabeth J., primary, Ward, Toby M., additional, Dean, Sonja, additional, Jegg, Anna, additional, Murugaesu, Nirupa, additional, Sims, David, additional, Lord, Christopher, additional, Ashworth, Alan, additional, Hnatyszyn, James, additional, Pegram, Mark, additional, and Lippman, Marc, additional

Published
2011
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20. Rescue of tropomyosin deficiency in Drosophila and human cancer cells by synaptopodin reveals a role of tropomyosin ? in RhoA stabilization.

Author

Wong, Jenny S, Iorns, Elizabeth, Rheault, Michelle N, Ward, Toby M, Rashmi, Priyanka, Weber, Ursula, Lippman, Marc E, Faul, Christian, Mlodzik, Marek, and Mundel, Peter

Subjects
TROPOMYOSINS, DROSOPHILA, CANCER cells, GENE expression, CELL compartmentation, CELL migration, CELL differentiation
Abstract

Tropomyosins are widespread actin-binding proteins that influence numerous cellular functions including actin dynamics, cell migration, tumour suppression, and Drosophila oocyte development. Synaptopodin is another actin-binding protein with a more restricted expression pattern in highly dynamic cell compartments such as kidney podocyte foot processes, where it promotes RhoA signalling by blocking the Smurf1-mediated ubiquitination of RhoA. Here, we show that synaptopodin has a shorter half-life but shares functional properties with the highly stable tropomyosin. Transgenic expression of synaptopodin restores oskar mRNA localization in Drosophila oocytes mutant for TmII, thereby rescuing germline differentiation and fertility. Synaptopodin restores stress fibres in tropomyosin-deficient human MDA-MB 231 breast cancer cells and TPM?-depleted fibroblasts. Gene silencing of TPM? but not TPM? causes loss of stress fibres by promoting Smurf1-mediated ubiquitination and proteasomal degradation of RhoA. Functionally, overexpression of synaptopodin or RhoA(K6,7R) significantly reduces MDA-MB 231 cell migration. Our findings elucidate RhoA stabilization by structurally unrelated actin-binding proteins as a conserved mechanism for regulation of stress fibre dynamics and cell motility in a cell type-specific fashion. [ABSTRACT FROM AUTHOR]

Published
2012
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