CHEM495 - High Throughput Discovery: A Multidisciplinary Approach To Cancer.

The newly developed massively parallel technologies have enabled the simultaneous analysis of many pathways. There are several large scale international efforts to probe the genetics and drug sensitivity of cancer cell lines. However, there are some rare cancers that have not been analyzed in depth. One of these rare cancers is malignant peripheral nerve sheet tumors (MPNST). MPNST, although a rare cancer, are common in patients with neurofibromatosis type. In the course, students will take part in a high throughput discovery effort in two phases. Phase 1 is a training phase, which will consist of quantitative profiling the sensitivity of MPNST cell lines to a library of >120 common and experimental cancer drugs. These will be conducted in the UPenn High Throughput Screening Core. (http://www.med.upenn.edu/cores/High-ThroughputScreeningCore.shtml). While we call this a training phase, the data from this will be subject to rigorous quality control for eventual publication and development of a public database for rare tumors. Phase 2 is an independent research project. Examples of projects include, but are not limited to: Combinatorial screens (synthetic lethal); siRNA screens; novel compound screens; determining mechanisms of cell death; developing tools for data analysis and database development. During phase 2, students will also modify compounds of interest using the Penn Chemistry: Upenn/Merck High Throughput Experimentation Laboratory (https://www.chem.upenn.edu/content/penn-chemistry-upennmerck-high-throughput-e xperimentation-laboratory), and then retest them for activity to determine structure activity relationships. We will sponsor phase 2 projects relevant to neurofibromatosis. However, in phase two students can also research other areas if they develop sponsorships from professors. We expect the course to be a hypothesis engine that generates ideas for further research. Prerequisites include a strong foundation in biology and chemistry. Students will prepare an abstract proposal by week three on their phase 2 project, and a report, in scientific paper style, due on the last day of the semester.