Shiaw-Yih (Phoebus) Lin Laboratory

Our Research Focus

Our research starts with understanding DNA damage signaling, including genetic and chromatin remodeling mechanisms. We discovered BRIT1's essential function in DNA damage response and established it as a bona fide tumor suppressor gene. Building on this foundation, we have developed predictive signatures for three DNA replication issues:

• Homologous recombination deficiency (HRD)
• Mismatch repair defect (MMRD)
• Replication stress response defect (RSRD)

These predictive signatures have proven highly effective in identifying patients across multiple cancer types who are most likely to respond to specific treatments, such as PARP inhibitors and immunotherapy.

Currently, our research focuses on enhancing cancer immunotherapy treatments by converting immunologically "cold" tumors to "hot" tumors. We do this by targeting replication stress and DNA repair pathways, particularly RNase H2 inhibition and TREX1 targeting, which generate signals that stimulate the immune system in the tumor microenvironment. Our research has demonstrated that these approaches can effectively sensitize resistant tumors to immune checkpoint blockade.

Our multidisciplinary approach to research combines systems biology and genomics with mechanism-based biomarker development and targeted therapeutic strategies. We aim to revolutionize cancer treatment by exploiting specific DNA repair deficiencies to enhance both targeted therapy and immunotherapy responses.

Learn more about our research