Our research

Cells incorporate a large number of internal and external cues as they execute biological programs. The treatment of human disease induces complex molecular changes across these programs. These changes depend on the mechanism of action of the applied therapy as well as due to differences in genetic background across patients. Defining the regulation of these innate and treatment-induced landscapes can identify successful points of therapeutic intervention. The Chemical Genomics Laboratory at Columbia aims to leverage cutting-edge multiplex single-cell genetic and chemical genomics tools to generate these comprehensive maps of cellular response.

Our approach

sci-Plex nuclear hashing enables the coupling of high-throughput chemical screens to single-cell combinatorial indexing RNA-seq. This platform enables the characterization of the effects of perturbation across thousands of unique “cell model x drug” combinations uncovering transcriptional signatures that vary by exposure and cell type/cell state.

Single-cell CRISPR screens allow for the molecular characterization of the effect of many genetic perturbations in parallel. Combined with chemical transcriptomics these screens enable the dissection of the contribution of individual genes to drug-induced transcriptional programs.

We are interested in leveraging our tools for single-cell perturbation screens to determine how genetic and chemical perturbations interact to drive therapeutic response in the context of complex in vivo cell-cell interactions.