Center Initiatives
DF/HCC Strategic Initiatives
Cancer Drug Discovery (CDD)
Cancer Drug Discovery
The Cancer Drug Discovery (formerly known as Cancer Drug Assays) strategic initiative is designed to assist in development of new cancer therapeutics based upon research conducted by DF/HCC investigators. CDD offers three services:
- Target Identification and Validation. This newly formed service performs shRNA screens to knock down expression of genes of interest. CDD uses the lentiviral shRNA library from The RNAi Consortium at the Broad Institute, which aims to generate 75,000 shRNA constructs specific for 15,000 human genes in an arrayed format, together with high-throughput viral production and robotic screening capabilities. shRNAs targeting up to 10,000 human genes are expected to come online in the near future.
- Protein Expression. This service uses the baculovirus insect cell expression system to produce milligram quantities of native folded recombinant proteins. This Core uses the sequence-verified cDNA collections at the Harvard Institute of Proteomics to allow rapid production of recombinant viruses without needing the investigator to supply cDNAs for expression constructs. This process allows rapid production of epitope-tagged protein for facile purification.
- Assay Development and HTS. This Core assists in developing in vitro or cell-based screening protocols. In addition, the HTS Core uses a small molecule library of over 100,000 compounds and a robotics platform to perform high-throughput screening to identify small molecule inhibitors.
In addition to these services, CDD staff members are available for consultation on drug discovery projects. During the past year, CDD has established the shRNA and baculovirus Cores, assisted in the development of multiple HTS assays, and performed several successful small molecule screens in cell-based assays. A total of over 500,000 data points have been collected in these screens, and several large shRNA screening projects are planned for upcoming months.
CDD was formed after a series of discussions within the DF/HCC community that highlighted the need to assist DF/HCC investigators in capitalizing on their research and allowing them to speed cancer drug development efforts. CDD has oversight from a scientific advisory board chaired by Dr. Ed Harlow, with representatives from all DF/HCC institutions. Members of the CDD Scientific Advisory Board include Dr. Lewis Cantley (BIDMC), Dr. Robert D’Amato (TCH), Dr. Bruce Demple (HSPH), Dr. D. Gary Gilliland (BWH), Dr. Randall King (HMS), Dr. Peter Lansbury (BWH), Dr. Benjamin Neel (BIDMC), Dr. Thomas Roberts (DFCI), Dr. Jeffrey Settleman (MGH), Dr. Sander Van Den Heuvel (MGH), Dr. Junying Yuan (HMS), Dr. Zhi-Min Yuan (HSPH), and Dr. Bruce Zetter (TCH). As a member of the DF/HCC community, CDD is responsive to the community and welcomes inquires from DF/HCC investigators with interest in drug discovery. For more information on CDD, visit http://cda.med.harvard.edu.
