Research in the D’Orso lab focuses on understanding how gene regulatory programs operate in the context of normal and disease states, as well as during host-pathogen interactions. Regulation of transcriptional programs plays major roles in human health and disease. These programs regulate key cellular processes (differentiation, development, responses to environmental cues). Thus, their dysregulation promotes malignancy.
In addition, many pathogens hijack these regulatory networks to generate a permissive environment for replication and spread, thus affecting the host. However, a complete understanding of these processes is lacking. We are interested in discovering novel regulatory mechanisms that contribute to normal cell functioning and elucidating how their activity becomes dysregulated in disease states. Through these studies we hope to elucidate novel targets that can be exploited therapeutically for both viral infections and cancer.
Normal cells utilize transcription-epigenetic programs to control most biological processes. In these programs, recognition of the histone code by epigenetic “readers” allows transduction of complex chromatin modification patterns for specific biological outcomes. Recent findings have strongly implicated dysregulation of epigenetic instructions in viral infections and cancer, where growth-driving genes are robustly expressed and immune defense genes are repressed. While viruses rewire host cell gene regulatory programs to generate a permissive environment for replication and pathogenesis, genetic alterations in cancer cause dysregulation of gene expression programs for cancer cell survival. These abnormal programs create disease dependencies on certain master regulators of gene expression leading to “Transcriptional Addictions” thereby generating genetic vulnerabilities that could be manipulated therapeutically.