Epigenetic Regulation of Normal and Malignant Hematopoiesis

The Figueroa lab studies the role of epigenetic modifications in transcriptional regulation during normal and malignant hemopoiesis. Our focus is mainly on how changes in normal DNA methylation and hydroxymethylation patterns occur during malignant transformation and how these changes may contribute to the leukemogenic process. Using genome-wide approaches we have demonstrated that epigenetic changes in leukemic cells occur in an organized fashion and that they are dependent on the genetic context of the disease, so that different leukemia subtypes present with a unique epigenetic signature that defines them. However, despite these subtype-specific differences, we have also identified the existence of a common core of epigenetic abnormalities that occur in a recurrent manner in all leukemia subtypes, irrespective of genetic context. In the lab we are interested in understanding how these two distinct types of epigenetic lesions (i.e. subtype-specific and universal) occur and how they contribute to the process of malignant transformation. We use a combination of computational approaches based on genome-wide next generation sequencing data as well as in vitro and in vivo modeling to determine the consequences of the epigenetic lesions that we have identified.