Like a diamond, herpesviruses are forever! The lab focuses on human cytomegalovirus (HCMV), a beta-herpesvirus that infects most of the human population. HCMV generally remains asymptomatic in immunocompetent individuals, but may lead to significant morbidity and mortality in immunocompromised individuals and during congenital infections. HCMV establishes lifelong infection in its host and undergoes repeated cycles of latency and reactivation. The host immune system must constantly monitor the status of this virus and memory inflation occurs as a result. Memory inflation is being associated with an age-related impaired immune system. HCMV is also slowly being associated with other age-related diseases such as cardiovascular disease and cancer.
The major focus of the lab is to provide a molecular understanding of how HCMV manipulates host cell metabolic and differentiation pathways. To replicate, HCMV must modulate host cell metabolic pathways to provide the biosynthetic materials necessary for lytic replication. HCMV infection increases glycolysis and oxidative phosphorylation (OXPHOS) in infected cells. Surprisingly, this virus modulates host cell metabolic pathways in ways strikingly similar to those described in cancer. The long-term goal is to identify key metabolic pathways or metabolites that are required for HCMV replication that may be exploited for clinical applications. Our previous work has shown that HCMV manipulates the differentiation potential of adult stem cells. We showed that adipose-derived stromal/stem cells undergo abortive adipogenic differentiation after infection with HCMV. Adipogenic-like differentiation has been reported in infected fibroblast cells. We have also shown that HCMV manipulates the Wnt/β-catenin pathway. We have several projects and underway including:
- Alterations to mitochondrial function after HCMV infection
- Can HCMV induce a reverse Warburg phenotype?
- HCMV infection of adipose tissue
- Can HCMV alter global metabolic homeostasis?
- Manipulation of metabolic signaling pathways during HCMV infection
- Can we identify key metabolic pathways or metabolites that are required for HCMV infection that may be exploited for clinical applications?
- Establishing relevant murine CMV models
- Can a murine model of persistent CMV infection, be used to explore the relationship between CMV and age-related diseases?