Our research interests include:
- The molecular switch controlling HCMV latency and reactivation. Latency is an important and poorly understood aspect of virus biology. We seek to define the the transcriptional networks and virus-host interactions differentially controlling these patterns. This includes understanding their dependence on cell type (e.g., epithelial, endothelial, hematopoietic) or differentiation state, to regulate the entry into and exit from latency.
- DNA damage repair and replication. Many viruses are subject to DNA repair and/or make use of cellular repair machinery during their life cycles. We seek to define how HCMV hijacks and modulates host DNA repair and replication pathways to maintain viral genome integrity and modulate viral genome conformation for replication and latency. This work also provides novel insights into DNA replication and repair strategies in human cells \t.
- Innate signaling. Innate signaling is the first line of defense in viral infection and a defense that HCMV skillfully navigates and perhaps uses for viral sensing. We seek to define how HCMV subverts and commandeers interferon signaling in navigating decisions to establish latency or reactivate from latency.
- Nuclear receptor signaling. Nuclear receptors integrate a number of signals through the host and have important implications for host biology and virus infection. Sterol signaling and the nuclear receptors responding play important, but poorly defined roles in virus infection. We seek to understand how HCMV regulates and is regulated by cholesterol signaling to make decisions to enter into or exit from latency.
- HCMV modulation of barrier function and intestinal health. HCMV is associated with worse outcomes in intestinal disease. Using human intestinal organoids, we seek to define how HCMV impacts differentiation, proliferation, and function of the colonic epithelial cellular barrier through the modulation of host signaling pathways important to differentiation, proliferation and repair. This work will contribute to poorly understood roles of CMV in inflammatory bowel disease, ulcerative colitis, and Crohn’s disease.
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