Our group studies the genome surveillance and repair systems in vertebrates. We are particularly interested in understanding how cells maintain the integrity and stability of the genome when DNA double-strand breaks, the most dangerous type of DNA damage, occur in chromatin. Genetic mutations that compromise the ability of cells to properly sense and repair DNA double-strand breaks cause many human diseases such as cancer. We employ multiple experimental systems including Xenopus egg extracts and human cells to dissect the DNA damage signaling and repair networks. In addition, we utilize a “laser scissors” technology in couple with advanced imaging tools to visualize the DNA damage response in individual cells. By understanding the basic mechanisms of genome maintenance, we hope to contribute to understanding of the process of tumorigenesis and the development of new cancer therapeutics.

Image at left: A 532-nm short-pulsed laser microbeam was directed to create DNA damage sites in a line pattern in human U2OS cell nuclei. Indirect immunofluorescence staining indicates that NBS1, a nuclear protein involved in DNA double-strand break sensing and repair, was recruited to and accumulated at the laser-induced DNA damage sites.

Image at left: DNA double-strand breaks were generated in a line pattern in a human U2OS cell nucleus by a 532 nm laser microbeam. Subsequent live cell imaging analysis indicates that the NBS1 protein fused to YFP (NBS1-YFP) was readily recruited to the DNA damage sites. (View the movie in QuickTime format here).