MOLECULAR GENETICS AND EPIGENETICS (GEN) – PROJECT SUMMARY/ABSTRACT The accumulation of heritable genetic and epigenetic changes that result in the loss of tumor suppressors and/or inappropriate activation of proto-oncogenes is a hallmark of cancer. The goals of the Molecular Genetics and Epigenetics Program (GEN) are to understand the molecular mechanisms that underlie these defects and to unleash the potential of precision medicine. The Program capitalizes on the large number of outstanding investigators at UVA with research expertise in chromatin architecture, transcription, replication, DNA repair, genomics, epigenomics and cellular checkpoints in cancer. The Members are organized around three main themes: (1) chromosome function, malfunction, and cellular checkpoints; (2) changes to gene expression and epigenetics that drive cancer; and (3) cancer bioinformatics. H. Li and Stukenberg bring complementary clinical/translational and fundamental biological expertise to lead GEN. The Program has 24 current members from one school and seven departments. Eight of these individuals are new to the Program or to UVA since the last renewal. They bring considerable expertise in the bioinformatics of microarray and deep-sequencing data, large-scale genomic rearrangements, the molecular effects of and cellular responses to radiation, computational biology, and epigenetics, maintaining our strength in that area. Program Members are principal investigators of grants totaling $5.04M of direct cost peer-reviewed funding, of which $1.55M is from NCI and $3.49M from other peer-reviewed sources. GEN Members rely on infrastructure provided by the UVACC, particularly the Advance Microscopy Facility, Flow Cytometry Core, and the Molecular and Immunological Translational Science Core. GEN is composed of highly productive and collaborative members with 169 selected publications since the last grant period. Of these, 40% have an impact factor of 10 or greater, 27% are intra-programmatic, 22% are inter-programmatic with other UVACC Programs, and 20% are collaborative with other NCI Cancer Centers.