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Felicia Goodrum, PhD

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Professional Interests

Our laboratory is broadly interested in complex interactions between DNA viruses and their host cells that allow viruses to subvert or co-opt cellular processes for viral objectives. Viruses are at once phenomenal molecular machines capable of overtaking complex organisms and powerful tools for understanding cell biology. Through co-evolution, herpesviruses have mastered our biology, skillfully manipulating the host to achieve an extraordinary coexistent latent state that enables the virus to persist indefinitely in the immunocompetent host. Human cytomegalovirus (HCMV) is the largest, most complex virus known to infect humans and asymptomatically infects most of the population worldwide. Like all herpesviruses, HCMV establishes a lifelong latent infection, sporadically and subclinically reactivating in the healthy host with life-threatening disease risk in the immunocompromised or immune naive host. HCMV infection or reactivation carries life-threatening human health risks in the context of a congenital infection or inadequate adaptive immune responses, particularly in the context of transplantation. CMV is also emerging as an important co-factor in aging, cancer, and gastrointestinal disease (e.g., ulcerative colitis). In addition to the risks to human health, HCMV is a powerful tool for understanding biological host process as it has evolved to target or manipulate the most pivotal points in almost any host process. Our laboratory seeks to define the virus-host interactions important for the virus to “sense” and “respond” to host cues and filter noise in the system to switch between latent and replicative states. This foundational knowledge is key to controlling HCMV pathology and will broadly define strategies by which viruses integrate into host cell biology. Our research interests include:
1. The molecular switch controlling HCMV latency and reactivation. Latency is an important and poorly understood aspect of virus biology. We seek to define the complex transcriptional patterns and the virus-host interactions differentially controlling these patterns, as well as their dependence on cell type (e.g., epithelial, endothelial, hematopoietic) or differentiation state, to regulate the entry into and exit from latency.
2. 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 that have been primarily understood in yeast.
3. 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.
4. Liver X receptor (sterol) signaling. 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.
5. 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.

Grant Information

R37 AI079059 MERIT Mechanisms of Human Cytomegalovirus Latency in Primary Human Hematopoietic Cells
R01 AI169728 Virus-host interactions regulating innate signaling for human cytomegalovirus latency
R01 AI177392 Host DNA Repair Pathways in Human Cytomegalovirus Replication
P01 AI127335 Dysregulation of host hematopoietic progenitor cell signaling pathways to modulate latency and reactivation
R01 DK137411 Modulation of colonocyte barrier function and signaling by cytomegalovirus

Biography

Felicia Goodrum is a Professor in the Department of Microbiology and Immunoology in the Geisel School of Medicine at Dartmouth. Dr. Goodrum’s scholarship is focused on virus-host interactions important for viruses to establish life-long latent infections and to make the decision to reactivate a program of replication. Her laboratory has identified viral genes and the host pathways they target to define the biology important to latency and reactivation. Dr. Goodrum’s work has been recognized through Leukemia and Lymphoma Society fellowships, the Howard Temin Award from the National Cancer Institute, the Pew Scholar in Biomedical Sciences Award, Kavli Young Investigators Award, the Presidential Award for Early Career Scientists and Engineers, and a National Institutes of Health MERIT award. She is past-President of the American Society for Virology and co-Editor-in-chief for the premier virology journal, Journal of Virology. Dr. Goodrum is an active advocate for science in society.