About

Immune Activation: Extrachromosomal DNA, when found in normal cells, stimulates a potent anti-tumor immune response. However, CIN-high tumor cells frequently produce extrachromosomal DNA but have evolved mechanisms for evading this immune-mediated destruction. We are integrating computational and experimental methods to identify novel, targetable immune-evasive mechanisms used by CIN-high tumor cells. With this approach we can reinvigorate antitumor immunity against chromosomally unstable cancers, which are generally less responsive to currently available immune-oncology agents.

Synthetic Lethality: Synthetic lethality is a well-established genetic approach of target discovery that involves exploiting vulnerabilities in tumor cells to induce tumor cell death while sparing normal cells. Cells selected for increased rates of mitotic errors, a hallmark of CIN-high cells, have unique dependencies that can be selectively targeted with novel therapies. We are identifying these targets by combining computational analysis with genome-wide experimental screens leveraging our proprietary CIN-high/CIN-low paired cancer cell lines. We have found targets involved in mitotic checkpoints, centrosome regulation and kinetochore-microtubule dynamics, as well as several other pathways. While synthetic lethality has been used for drug discovery in the past none have used a CIN specific approach in looking for vulnerabilities unique to CIN-high cells, until now.