Maintenance of genome stability is extremely important in the cell cycle because instable genome is the primary contribution to cancer formation. Cells have evolved multiple mechanisms to prevent genomic instability during genome duplication, including DNA damage checkpoint, DNA damage repair, regulation of DNA replication, etc. The objective of our research is to investigate the mechanisms of how our cells maintain the stability of their genome and to utilize this information to identify new drugs for cancer treatment. To accomplish this goal, we are conducting following research work. (1) Investigate the mechanisms of how cells response to DNA damage and repair damaged DNA. (2) Identify new compounds targeting DNA replication apparatus through high throughput screening (HTS) assays, and investigate the mechanisms of anti-cancer drug resistance to improve cancer treatment. (3) Investigate how cells prevent DNA re-replication (one type of genomic stability) in both normal and cancer cells. (4) Identify small molecules that selectively kill cancer cells by inducing DNA re-replication via HTS.