Dr. Greenberg’s laboratory investigates molecular mechanisms that control genome integrity and their impact on carcinogenesis and responses to anticancer therapies. The central importance of this topic to cancer etiology and treatment is prominently illustrated by hereditary breast and ovarian cancer syndrome, which is caused by germline mutations to the breast cancer early-onset genes, BRCA1 and BRCA2. The lab’s studies have contributed to the concept of a BRCA1-centered DNA repair and tumor suppressor network, having led to the discovery of three new breast cancer susceptibility genes. A second area of interest is the complex relationship between chromatin structure and DNA repair. They have developed novel systems to investigate interrelationships between chromatin structure and DNA damage signaling. Using these approaches, Dr. Greenberg’s lab has demonstrated that nondegradative forms of ubiquitin are required for BRCA1 localization to genomic sites of DNA damage and that combinatorial acetylation and methylation on histone H4 profoundly influences DNA repair mechanism and response to therapy. Additionally, they have shown that persistent double-strand breaks silence transcription along large stretches of chromatin in cis to the site of DNA damage. The Greenberg lab intends to utilize these systems to reveal new insights into the interplay between chromatin structure and DNA repair and how DNA damage responses influence diverse biological phenomena including cellular senescence and viral latency. Their overarching goals are to utilize information gained from these basic studies to identify candidate cancer susceptibility genes and to devise mechanisms to exploit DNA repair deficiencies for targeted therapy of cancer.