My research interests focus on gene regulation in both normal differentiation and cancer. Over the past 32 years my laboratory has made seminal contributions to understanding the role of gene regulation in cell differentiation and the role of disruption of these pathways in leukemia, lung cancer, and liver cancer. These efforts have included basic studies understanding gene regulation in normal and leukemic hematopoietic stem cells, leading to development of novel ways of manipulating gene expression and exploiting differences between normal and leukemic stem cells as a basis for targeted therapy, and the role of stem cell oncofetal proteins in leukemia and solid tumors, especially in liver cancer. In addition to my role as PI on many individual NIH R01 grants, I have also served as PI on Program Project grants and as Director of the Blood Program of the Harvard Stem Cell Institute. My recent studies have focused on noncoding RNAs, and include published findings on antisense RNAs, RNA editing, and noncoding RNAs in gene regulation, methylation, and cancer. Our most recent studies demonstrated that RNA can regulate DNA methylation, and that RNA can be utilized to induce demethylation in a gene-specific manner. If successful, potential future clinical applications could include the ability to specifically reverse disease related DNA methylation, such as methylation and/or of tumor suppressor genes. I have been senior investigator on a number of studies investigating the role of tumor suppressor genes, such as CEBPA, in lung cancer, as well as studies of mechanisms of resistance to EGFR tyrosine kinase inhibitors in this disease.