Daniel Rines, Ph.D.
Research Investigator I
Our system for high throughput acquisition and analysis of cellular image data, known as high content screening (HCS), has enabled the analysis of complex phenotypes not readily measurable with standard reporter gene methodologies. It is now possible to examine changes in sub-cellular protein localization, morphological alterations, cellular migration, or cytoskeletal rearrangements in an automated fashion.
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An important focus of our research is the development and implementation of this technology to enhance cell-based screening. We are using these technologies to complete screens of both genomic and small molecule libraries. The application of this technology to functional genomics is enabling the quantitative analysis of discrete molecular phenotypes on a genome-wide scale. In addition to screening chemical libraries for the discovery of potential therapeutics, we are using this approach for the identification of new fluorescent reagents of organelle function and disease biomarkers.
The wealth of information acquired through high content screens requires innovative ways to interpret and mine vast amounts of data. Thus, we have established several collaborations with academic labs to develop intelligent multiplexed analyses. The combined application of these technologies is stretching the boundaries of bioinformatics and creating exciting opportunities in drug discovery.
Basic Research
The mitotic spindle is an attractive target for cancer therapies, especially given that several anti-mitotic agents have been commercial successes. Focusing on identifying novel genes involved in mitotic spindle assembly using phenotypic screens similar to those described above, we have recently discovered a number of novel genes involved in spindle structure and function.
In our studies, we are using these novel components to examine the mechanical properties of the spindle and to elucidate those that could be potential drug targets. The ultimate goal of this research is to identify new therapeutics that offer better specificity over existing agents and, even more excitingly, potentially novel mechanisms of action.
Selected Publications
- Rines DR, Tu B, Miraglia L, Hull MV, Orth AT, Chanda SK. High-content screening of functional genomic libraries. Methods Enzymol. 2006; (In Press).
