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Isakoff, Steven

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Isakoff

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Steven

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Isakoff, Steven

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2008 - 20102

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Author's Publications: search.filters.isAuthorOfPublication.4830d33e-cb92-4866-8473-25ca7f3fb895

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    Rapid targeted mutational analysis of human tumours: a clinical platform to guide personalized cancer medicine
    (WILEY-VCH Verlag, 2010) Dias-Santagata, Dora; Akhavanfard, Sara; David, Serena S; Vernovsky, Kathy; Kuhlmann, Georgiana; Boisvert, Susan L; Stubbs, Hannah; McDermott, Ultan; Settleman, Jeffrey; Kwak, Eunice Lee; Clark, Jeffrey; Isakoff, Steven; Sequist, Lecia; Engelman, Jeffrey A; Lynch, Thomas J; Haber, Daniel; Louis, David; Ellisen, Leif; Borger, Darrell; Iafrate, Anthony
    Targeted cancer therapy requires the rapid and accurate identification of genetic abnormalities predictive of therapeutic response. We sought to develop a high-throughput genotyping platform that would allow prospective patient selection to the best available therapies, and that could readily and inexpensively be adopted by most clinical laboratories. We developed a highly sensitive multiplexed clinical assay that performs very well with nucleic acid derived from formalin fixation and paraffin embedding (FFPE) tissue, and tests for 120 previously described mutations in 13 cancer genes. Genetic profiling of 250 primary tumours was consistent with the documented oncogene mutational spectrum and identified rare events in some cancer types. The assay is currently being used for clinical testing of tumour samples and contributing to cancer patient management. This work therefore establishes a platform for real-time targeted genotyping that can be widely adopted. We expect that efforts like this one will play an increasingly important role in cancer management.
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    Identification of Novel Pro-Migratory, Cancer-Associated Genes Using Quantitative, Microscopy-Based Screening
    (Public Library of Science, 2008) Naffar-Abu-Amara, Suha; Shay, Tal; Galun, Meirav; Cohen, Naomi; Isakoff, Steven; Kam, Zvi; Geiger, Benjamin
    Background: Cell migration is a highly complex process, regulated by multiple genes, signaling pathways and external stimuli. To discover genes or pharmacological agents that can modulate the migratory activity of cells, screening strategies that enable the monitoring of diverse migratory parameters in a large number of samples are necessary. Methodology: In the present study, we describe the development of a quantitative, high-throughput cell migration assay, based on a modified phagokinetic tracks (PKT) procedure, and apply it for identifying novel pro-migratory genes in a cancer-related gene library. In brief, cells are seeded on fibronectin-coated 96-well plates, covered with a monolayer of carboxylated latex beads. Motile cells clear the beads, located along their migratory paths, forming tracks that are visualized using an automated, transmitted-light screening microscope. The tracks are then segmented and characterized by multi-parametric, morphometric analysis, resolving a variety of morphological and kinetic features. Conclusions: In this screen we identified 4 novel genes derived from breast carcinoma related cDNA library, whose over-expression induces major alteration in the migration of the stationary MCF7 cells. This approach can serve for high throughput screening for novel ways to modulate cellular migration in pathological states such as tumor metastasis and invasion.