Research in the laboratory of Yuichi Machida, Ph.D., focuses on how cells respond to DNA damage. Genomic DNA, which stores all genetic information, is under constant attack by environmental factors such as sunlight, dietary carcinogens and tobacco smoke. Resulting DNA lesions could cause DNA mutations and breaks, which are the hallmarks of cancer.
Fortunately, an array of repair mechanisms exists to eliminate DNA lesions. Termed DNA caretakers, these molecular custodians provide a first-line defense against cancer by maintaining the integrity of the genomic DNA. Dr. Machida is interested in how these DNA caretakers prevent DNA mutations and breaks when DNA is damaged.
- DNA damage and mutations. Dr. Machida's team is one of the groups that discovered a new DNA caretaker protein, Spartan (DVC1), which is important to prevent mutagenesis caused by DNA damage. By studying this newly identified protein, Dr. Machida's research provides new insights into how mutations in the genome are prevented.
- DNA damage and chromosome breaks. Dr. Machida is interested in how cells prevent chromosome breaks. Dr. Machida's research demonstrated that a newly discovered caretaker protein, FAN1, is important to prevent chromosome breaks after DNA damage. In addition, Dr. Machida's team showed that cancer cells could be sensitized to a class of anti-cancer drugs by lowering the levels of FAN1 proteins.
Significance to patient care
Many anti-cancer therapeutics, including radiation and cancer drugs, work by damaging the genomic DNA of cancer cells. A better understanding of DNA damage response in cancer cells will help enhance the toxicity of anti-cancer drugs and improve the clinical outcomes of various chemotherapeutic strategies.