DNA damage, repair, replication, and mutagenesis
Cancer is a genetic disease, which often involves mutations in critical genes such as tumor-suppressor genes and oncogenes. The human genome is persistently attacked by DNA damaging agents, such as reactive oxygen species and alkylating agents, to form various DNA lesions. The vast majority of DNA lesions are removed by DNA repair machinery (e.g., base excision DNA repair, nucleotide excision DNA repair), but a small portion of the lesions evade the repair mechanisms and induce mutations during replication. We are currently evaluate the effects of DNA alkylation, oxidation, halogenation, and platination on DNA replication and mutagenesis.
Developing platinum-based chemotherapeutics: Platinum-based agents are among the most widely prescribed chemotherapeutic drugs. Cisplatin and its analogs are used to treat approximately half of all cancer patients receiving chemotherapy. The antitumor activity of cisplatin mainly stems from its ability to form intrastrand cross-link, which deters DNA replication and transcription and initiates a signaling cascade that leads to cell death. The major limitation of the cisplatin-based chemotherapy is its resistance. Our research goal is to develop platinum-based anticancer agents with a new mode of action and a reduced resistance.
Developing cephalostatin-based chemotherapeutic drugs: Cephalostatin is an extremely potent anti-cancer marine natural product that has been suggested to alkylate DNA. The major hurdle in developing cephalostatin-based chemotherapeutic drugs is its availability. We seek to develop cephalostatin-based chemotherapeutics with a dramatically increased synthetic accessibility. .