Name: Forest Ray
Field of study: Cancer biology
Host institution: Watson School of Biological Sciences, Cold Spring Harbor
Mentor(s): Dr. Shilpi Paul, Dr. Alea Mills
Systematic scans of human tumors have revealed certain commonly deleted regions. One region frequently deleted in neuroblastoma, breast and several other cancers is the 1p36 interval of human chromosome 1, which has a homologous region in mouse chromosome 4. Recently, the Mills group discovered a tumor suppressor in this region called chromodomain helicase DNA-binding protein 51 (CHD5). Due to the high level of conservation between mouse and human Chd5, the use of chromosome engineered mouse models has proved feasible for studying CHD5 dysfunction. Chd5 positively regulates the p16Ink4a/Rb- & p19Arf /p53 pathways. Mice with a single deletion of the Chd5 interval have decreased expression of p16 and p191. However, the mechanism by which Chd5 modulates these genes remains unknown. Additionally, how tumor-derived mutations disrupt Chd5's tumor suppressive function is completely unknown. Recently, certain consistent mutations have been found in human tumors related to CHD53, but it is not known whether these mutations drive tumorigenesis or vice-versa. My goal over the summer has been to re-create these mutations in an inducible model using site-directed mutagenesis, implant them into mouse embryonic fibroblasts (MEFs) and to assess the resulting phenotypes in order to gain more insight into how mutation-derived dysregulation of CHD5 might play a role in cancer.