General Research InterestI am interested in lung cancer genetics, the mechanisms by which genetic and epigenetic alterations contribute to chemoresistance of cancer therapeutics, and evaluations of novel chemotherapeutic agents with animal models
Research Description(1) Targeting cancer cells containing mutant p53: p53 mutations are reported in 50-60% of non-small cell lung cancers and in up to 90% of small cell tumors, thus p53 represent a common mutation in this malignancy. Studies have shown that restoring wild type p53 function leads to regression of cancers. An ideal anti-cancer treatment is the anti-cancer agent can induce death of cancer cells, but is less toxic to normal cells. The novel small molecule PRIMA-1 (p53-dependent reactivation and induction of massive apoptosis) has been shown to induce apoptosis in human tumor cells containing mutant p53. We are investigating in the role of PRIMA-1 in apoptosis using human lung cancer cell lines and murine lung cancer models. We are especially interested in the relationship between PRIMA-1 and microRNAs in apoptotic pathway in spontaneous non small cell lung cancers. This project is funded by Joan’s Legacy and LUNGevity Foundation. (2) Analysis of Fanconi Anemia (FA)/BRCA pathway for cancer treatment : The Fanconi Anemia (FA)/BRCA pathway is essential for human cells to maintain integrity following DNA damage. Patients with FA defective tumors have been shown to be more sensitive to treatment with DNA interactive chemotherapeutic agents. Somatic defects in this pathway are likely to be present in sporadic tumors, but the complexity to evaluate each individual gene for genetic or epigenetic changes have prevented to take advantage of the presence of these defects to select the patients most likely to benefit from DNA breaking treatment. FANCD2 foci on chromatin can be appreciated when the function of this pathway is maintained. We are conducting research in solid tumor specimens of patients undergoing surgery to evaluate for an all inclusive method assessing the functionality of the Fanconi Anemia/BRCA pathway. This fluorescence staining based test could potentially lead to the identification of patients most likely to respond to DNA breaking agents or to agents inhibiting compensatory mechanisms of repair. A clinic trial is on going for patients with defective FA pathway.