Lauffenburger:Tharathorn Rimchala: Difference between revisions
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'''Cell Decision Model of Signaling in Endothelial Angiogenesis''' | '''Cell Decision Model of Signaling in Endothelial Angiogenesis''' | ||
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Signaling pathways downstream of VEGFA, Ang-1, and Ang-2 have been correlated to multiple angiogenic responses including survival vs. apoptosis, proliferation and migration. Yet, the existing pathway information is insufficient to quantitatively predict response in the presence of spatially and temporally varying levels of these growth factors during angiogenic sprouting. We | Signaling pathways downstream of VEGFA, Ang-1, and Ang-2 have been correlated to multiple angiogenic responses including survival vs. apoptosis, proliferation and migration. Yet, the existing pathway information is insufficient to quantitatively predict response in the presence of spatially and temporally varying levels of these growth factors during angiogenic sprouting. We propose a strategy to acquire a data-driven cue-signal-response model to predict endothelial cell responses. Using human lung microvascular cell line(hMVEC) as a model system, we measure the quantitative signaling data (the activation of signaling protein downstream of VEGFA, Ang-1, Ang-2) are using sensitive, high throughput bioplex assay and in-cell western blotting. At the same time, we measure cell proliferation, migration and survival vs. apoptosis decision using BrdU incorporation assay, single cell tracking, and TUNEL assay in high-throughput 96 and 384 well plate formats. To obtain differential signaling data, we perform the above measurements in the presence of VEGF, Ang-1, Ang-2, and their combinations. Using regularized regression methods such as partial least square regression, we can correlate the measured signaling data to the measured cellular responses to obtain a set of proteins whose changes in phosphorylation are predictive of proliferation, migration, and survival vs. apoptosis decision. | ||
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Revision as of 20:01, 29 May 2008
 Tharathorn (Joy) Rimchala (BE Doctoral) in collaboration with Prof. Roger Kamm, MIT Research Summary: Cell Decision Model of Signaling in Endothelial Angiogenesis Signaling pathways downstream of VEGFA, Ang-1, and Ang-2 have been correlated to multiple angiogenic responses including survival vs. apoptosis, proliferation and migration. Yet, the existing pathway information is insufficient to quantitatively predict response in the presence of spatially and temporally varying levels of these growth factors during angiogenic sprouting. We propose a strategy to acquire a data-driven cue-signal-response model to predict endothelial cell responses. Using human lung microvascular cell line(hMVEC) as a model system, we measure the quantitative signaling data (the activation of signaling protein downstream of VEGFA, Ang-1, Ang-2) are using sensitive, high throughput bioplex assay and in-cell western blotting. At the same time, we measure cell proliferation, migration and survival vs. apoptosis decision using BrdU incorporation assay, single cell tracking, and TUNEL assay in high-throughput 96 and 384 well plate formats. To obtain differential signaling data, we perform the above measurements in the presence of VEGF, Ang-1, Ang-2, and their combinations. Using regularized regression methods such as partial least square regression, we can correlate the measured signaling data to the measured cellular responses to obtain a set of proteins whose changes in phosphorylation are predictive of proliferation, migration, and survival vs. apoptosis decision. |
