Director: Anna Mandinova, MD, PhD
Co-Director: Sam Lee, Ph.D.
Chemical genetics involves the systematic use of small molecules as probes in complex biological systems. Numerous examples have demonstrated that chemical genetics can uncover previously hidden protein regulators while simultaneouly providing novel biological probe and lead candidates for therapeutic uses. The CBRC proposes to develop a “Chemical Genetics Core Facility” at the CBRC of Massachusetts General Hospital to help Harvard-affiliated skin researchers expand their ongoing and future projects employing systematic small molecule technologies. To maximize the effectiveness of this Core we will interact closely with unique Boston-based resources in the field of chemical genetics including the Chemical Biology Platform at the Broad Institute. Significant interest in this approach is demonstrated by several pilot studies involving chemical genetics already underway at CBRC. These projects have yielded significant preliminary results demonstrating the value of applying chemical genetic approaches to skin biology.
The objective of the Chemical Biology Core is to provide investigators with the following services:
1. Assay Development: Design an innovative, unbiased “chemical” approach for Investigators, whereby the specific goals of each scientific project will be adapted to meet the criteria for a successful screening approach. The Core will take advantage of its considerable experience with transcriptional assays in multiple cell lines and their adaptation for high-throughput screens.
2. Validation of positive hits: After establishing conditions for sensitivity, specificity, and reproducibility of individual assays, the Core will offer an algorithm for the validation of positive hits including “hit” evaluation and selection based on bioinformatic analysis, using direct access to the Computerized Compound Database (ChemBank).
3. Product optimization: The Core will assist with target identification, additional “hit-like” small molecule selection, and their appropriate modification for translational research.
