2013-09-09 08:06:58 - Geoffrey Bartholomeusz, Assistant Professor and Director of the siRNA Screening Service at the University of Texas MD Anderson Cancer Center, will speak about “The Third Dimension for High Throughput RNAi-Driven Target Identification” at the 8th Cell Based Assay & Screening Technologies Conference on November 6-8, 2013 in San Francisco, CA.
Although two-dimensional (2D) model systems have contributed to the understanding of tumor biology, these models fall short of reproducing the complex and dynamic environments of the tumor. This has led to the development of three-dimensional (3D) models, with the spheroid model being the most commonly used of these. Spheroid models take advantage of the cells’ natural tendency to aggregate and the cellular organization within the spheroids emulates the heterogeneity of solid tumors with necrosis and radiation-resistant hypoxic regions.
As the Director of the Screening Service at the MD Anderson Cancer Center, Dr. Bartholomeusz leads a team of highly trained individuals performing high throughput siRNA screens that utilize both 2D monolayer cell culture and 3D spheroid cell culture models. The team has
developed a 3D spheroid cell culture model to address their hypothesis that silencing targets that regulate tumor architecture will alter the integrity of the tumor, reduce the hypoxic state and sensitize the tumor to radiation and/or chemotherapy. They used this model to perform a high throughput RNAi screen that used the activation of HIF-1 as the readout for selecting hits from the primary screen, and used alterations of hypoxic status of the inner core of the spheroid in the final validation and selection of the top ranked hits.
Dr. Bartholomeusz will share how he and his team identified and validated 5 unique targets whose silencing alters the integrity of the spheroid architecture. These results signify that the features of the third dimension, hypoxia, morphology and the heterogeneous growth characteristics of spheroids not present in 2D monolayer cell cultures makes their model necessary for studies in tumor biology.
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