Genomic Approaches to Cancer
Our laboratory focuses on the genetic basis of cancer, with particular emphasis on the use of new genomic and computer science approaches to cancer diagnosis and cancer biology. Having pioneered the use of DNA microarrays, or DNA chips, for cancer diagnosis, we are currently extending these techniques to gain insight into the molecular basis of lymphoma, lung cancer, prostate cancer, melanoma, brain tumors, and multiple myeloma. New efforts are using systematic functional genomic methods, including RNA interference (RNAi), to identify tumor suppressor genes and find potential Achilles' heels of cancer that might represent new therapeutic targets. Work is also under way to develop proteomic approaches to cancer cell characterization, including advanced mass specrometry to identify activated kinases as well as proteins in blood samples that are diagnostic of cancer. Another area of research is the development of computational methods capable of extracting biologically or clinically meaningful signatures from complex genomic data. In addition, we are exploring novel approaches to the integration of genomics and chemistry. For example, we have established high-throughput screening methods for screening chemical compounds on the basis of their ability to modulate a gene expression signature of interest - a method particularly useful when the critical protein targets of a biological process are not yet known. Using this approach, called gene expression-based high throughput screening (GE-HTS), we have identified compounds capable of inducing the differentiation of acute myeloid leukemia (AML) cells. One of these compounds has advanced to clinical trial in patients with relapsed AML. Similar GE-HTS screening is in progress in models of androgen-dependent prostate cancer, neuroblastoma, Ewing sarcoma, sickle cell anemia, and embryonic stem cell differentiation.