Shen Laboratory

Currently the two biggest limitations hampering the effective treatment of gastrointestinal tumors are (1) a general lack of effective targeted therapies, and (2) a lack of predictive biomarkers to help oncologists identify which individual patients will benefit from either standard chemotherapy or the targeted therapies currently in development. Employing both experimental and computational scientists, the Shen Lab seeks to directly address both of these issues and in doing so improve the lives of colorectal and appendiceal cancer patients around the world.

The advent of Next-Generation Sequencing (NGS) technology has brought about the genomic era of medicine, and with over 100,000 tumors sequenced worldwide it is now abundantly clear that cancer is a tremendously heterogeneous disease. Like a snowflake, every tumor is unique. By pairing descriptive technologies (DNAseq, RNAseq, ChIPseq, RPPA) with high-throughput functional genomic screens using CRISPR-Cas9, we will now learn which of these differences are important and then use this knowledge to identify the best treatment for each patient.

Research Focus

• Systematic, multi-conditional genetic interaction mapping in cancer cell lines via combinatorial CRISPR-Cas9 screens.
• Identification, network characterization, and mechanistic investigation of conserved synthetic lethal interactions.
• Functional genomic screening in primary patient derived cell lines & PDX models.
• Hierarchical models of the cancer cell and machine-learning to predict drug response.
• Molecular characterization of appendiceal adenocarcinomas (AA) and testing of preclinical models to identify druggable AA specific vulnerabilities.
• Characterization of intratumor heterogeneity with single cell and spatially resolved sequencing techniques