Principal Investigator Tyler Jacks is a Daniel K. Ludwig Scholar
and Founding Director of the Koch Institute.

The Jacks Laboratory, having established a number of genetically-engineered mouse models of human cancer over more than 25 years, has focused increasingly on using these models to understand the molecular and cellular factors that control tumor evolution. Through the use of advanced genomic profiling, a number of important key regulators have been identified in small cell lung cancer, lung adenocarcinoma, and pancreas cancer. Importantly, the group’s research scope has also been extended to include immune cells, including natural killer (NK) cells, and how they are able to affect tumor evolution. The over-arching goal of this research is to translate the findings from mouse cancer models to human cancer, with the hope of developing therapies to inhibit tumor cells from advancing to the metastatic stage.

One area of focus in the Jacks group is small cell lung cancer (SCLC), a highly aggressive neuroendocrine lung tumor characterized by early and widespread metastasis. Decades of research have failed to yield significant improvement in treatment outcomes for SCLC patients, nor targeted therapies to show efficacy. The Jacks Laboratory uses a murine model of SCLC which involves the conditional deletion of tumor suppressor genes Trp53 and Rb1 in the lung epithelium. These animals develop lung tumors that frequently metastasize to distant organs such as the liver, mimicking a key feature of the human disease. The researchers have used this model, as well as derivative cell lines, to investigate various aspects of SCLC tumor progression and metastasis. They performed a CRISPR-based genetic screen to identify novel SCLC-specific vulnerabilities that may be potential therapeutic targets. By analyzing the results of the screen in parallel with other screens conducted by the group in lung adenocarcinoma and pancreatic ductal adenocarcinoma cell lines, they have identified a number of unique metabolic vulnerabilities in SCLC, which they are currently validating both in vitro and in vivo.

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