Chemical Biology: Shamji Group

Our group studies the relationship between disease genetics, pathophysiology, and the response to small molecules, with the goal of defining and testing strategies for therapeutic intervention in physiologically relevant models.

Our main projects include:

(1) Targeting cancer genetic dependencies. We use genomic cancer cell-line profiling to identify relationships between genetic features of human cancers and small-molecule sensitivity systematically. The goal is to guide discovery of drug-targetable dependencies associated with specific patient populations. This effort involves the study of existing drugs as well as the discovery of novel small-molecule probes against novel candidate oncogenes, such as metabolic enzymes and chromatin-modifying enzymes. This project is a collaboration with Stuart Schreiber and Paul Clemons's groups.

(2) Probing disease pathways in Crohn’s Disease (CD) and Type 1 Diabetes (T1D). We discover small-molecule probes for pathways implicated in CD/T1D by human genetics. The goal is to enable exploration of whether these pathways constitute useful targets for intervention in preclinical disease models. This project is a collaboration with Stuart Schreiber, David Altshuler, and Ramnik Xavier's groups.

(3) Use of profiling methodologies to study small molecules. We use profiling methods (imaging and gene expression) to annotate large collections of small molecules, especially those derived from diversity-oriented synthesis. The goal is to explore how profiling data can enable discovery of compounds with biological activities of interest, as well as reveal relationships between chemical structure and biological performance. This project is a collaboration with Paul Clemons, Stuart Schreiber, Anne Carpenter, and Todd Golub's groups.

Our group is largely supported by the National Cancer Institute and the Helmsley Charitable Trust.

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