The Epigenetics and Regulation Program aims to cultivate research collaboration among its members and with researchers or clinicians in other Programs, resulting in: 1) breakthroughs in understanding the basic mechanisms that regulate the growth and behavior of normal and cancer cells; and 2) translation of these basic findings into new methods for prevention, detection, prognosis, and treatment of cancer. The Program integrates research in epigenetics, gene regulation, signal transduction, and stem cell and developmental biology. With 22 members from 11 departments in three schools, the Program has made many basic and translational contributions: defining how DNA methylation of specific gene targets contributes to various types of cancer; showing a relationship between gene repression by the polycomb complex in stem cells and predisposition to aberrant DNA methylation in cancer cells; identification of a very tight association of the “CpG island methylator phenotype” (CIMP) with BRAF mutation in colorectal cancer; development and testing of more stable DNA methylation inhibitors as potential therapeutic drugs; development of endoplasmic reticulum stress protein Grp78 as a novel potential diagnostic tool and therapeutic target; use of Wnt pathway inhibitors to control stem cell proliferation versus differentiation; development of the first rat embryonic stem cells; discovery of a new potential tumor suppressor gene, Maf1; discovery of a transcriptional coregulator for the estrogen receptor, CCAR1, which controls breast cancer cell proliferation; identification of polymorphisms in enhancer elements which control cancer risk and transcription factor binding. Members of the Program interact via meetings designed to encourage inter- and intra-programmatic collaborations. Of the 392 papers published by members of the Epigenetics and Regulation Program over the last five years, 15% were intra-programmatic and 38% were inter-programmatic. Future directions include establishing an unrivaled international center of excellence in the area of cancer epigenetics through expanded faculty hiring; and expansion of our stem cell research capabilities. The Program is supported by $7.3 million in direct costs of peer-reviewed support of which $3.3 million is from the NCI.