Epigenetics is the study of phenotypic changes that are not mediated through mutations in the DNA sequence. The Cancer Epigenetics (CE) Program is focused on studying epigenetic changes, including modifications in DNA and RNA methylation/hydroxymethylation, histone modifications, and the function of a wide range of non-coding RNAs. Each of these components of epigenetic information has been found to play a critical role in cancer. Genetic mutations in genes involved in epigenetic-mediated mechanisms of gene regulation have been found in a broad array of solid tumors and hematologic malignancies. These genetic mutations occur in a great variety of epigenetic enzymes, such DNA methyltransferases (DNMT3A/B) and hydroxymethyltransferases (TET1/2), but also to epigenetic readers and writers (Polycomb-group proteins), and erasers of histone modifications (histone demethylases).
Another important area of investigation within the CE Program is elucidating the mechanisms by which epigenetic regulators orchestrate transcriptional programs in response to growth factor signaling and hormones and how such functional crosstalk is altered in cancer. Several laboratories also investigate how the chromatin architecture is altered in cancer, and how the interaction of oncogenes and enhancers is deregulated in solid and liquid tumors. Moreover, mutations in enhancer sequences themselves have also been shown to act as a contributing factor in cancer initiation and progression. These considerations form the basis of studies by a number of the Program members on the diverse mechanisms by which enhancer function is regulated through intrinsic and extrinsic signals and how such regulation is disrupted in cancer.
The Cancer Epigenetics members’ expertise is underscored within the three program aims, whose objectives are to explore multiple facets of epigenetic regulation in normal and cancer cells.
- Epigenetic Regulators: Elucidate the molecular mechanisms associated with epigenetic regulators mutated in cancer: Define the function of epigenetic regulators in cancer initiation and progression
- Signaling to Chromatin: Define the enhancer and transcriptional programming imposed through aberrant signal transduction cascades in cancer: Identify and elucidate the function of key epigenetic targets of aberrant growth signaling in cancer
- Translational Epigenetics: Validate epigenetic targets for therapeutic intervention and biomarker development in pre-clinical and clinical studies: Launch personalized epigenetic biomarkers and therapies to ameliorate cancer phenotypes
Cancer Epigenetics Training Program
- Ayad, Nagi G., Ph.D.
- de la Fuente, Macarena, M.D.
- Figueroa, Maria E., M.D.
- Harbour, J. William, M.D.
- Morey, Lluis, Ph.D.
- Nimer, Stephen D., M.D.
- Ramos, Juan C., M.D.
- Schürer, Stephan C., Ph.D.
- Shiekhattar, Ramin, Ph.D.
- Slingerland, Joyce M., M.D., Ph.D.
- Verdun, Ramiro E., Ph.D.
- Wahlestedt, Claes, M.D., Ph.D.
- Wang, Gaofeng, Ph.D.
- Watts, Justin M., M.D.
- Williams, Sion L., Ph.D.
- Xu, Mingjiang, M.D., Ph.D.
- Yang, Feng-Chun, M.D., Ph.D.
- Zhang, Yanbin, Ph.D.