Chioma Okeoma, PhD (Associate Professor)
Mechanisms of virus-host and tumor-host interactions
The interactions between the host and the viruses that infect the host or with diseases such as cancer extend well beyond the point of entry (for viruses) or local tissue microenvironment (for tumors). Yet we have only incomplete understanding of these interaction networks, which ultimately impedes our ability to prevent or mitigate diseases. My Lab focuses on understanding the role of host factors in protecting the host against pathogenic onslaughts or their involvement in the evolution of disease.
The long-term goal of my Lab is to elucidate the mechanism(s) by which host factors expressed in host cells or packaged into extracellular vesicles, such as exosomes regulate viral infections or facilitate disease manifestation, as in HIV and cancer. We utilize multifaceted approaches in our enquiries.
Ongoing research projects:
a. Exosomes in virus-host interactions: We discovered that exosomes in human semen contain factors that inhibit HIV. Consequently, identifying factors that confer this inhibitory effect, evaluating the effect of these exosomes on immune response against HIV, and understanding the factors that regulate exosome evolution have become important goals. We have conducted proteomic analyses of exosomal and non-exosomal soluble factors from seminal plasma and have identified proteins specific or common to both fractions. Projects in the lab aim to:
i. Validate multiple candidate proteins and to characterize their functions. Our goal is to identify exosome-based HIV inhibitors and/or biomarkers.
ii. Investigate the effect of exosomes on host immune response against HIV using both ectocervical explants and humanized mouse models.
iii. Investigate the influence of illicit drugs and other infective agents on the physiochemical properties and functions of biofluid exosomes and evaluate how illicit substances and infective agents affect exosome speciation.
b. Delineating the role of innate immunity in breast cancer development and progression:
BST-2 is an innate immunity protein with paradoxical roles. We have extensively shown that expression of BST-2 prevents the release of viral particles from host cells, resulting in inhibition of viral infection. Given the antiviral functions of BST-2, it was not to be expected that BST-2 has protumor functions. However, recent studies from our Lab show that elevated levels of BST-2 positively correlates with breast cancer aggressiveness. We have identified the domains of BST-2 that control different cancer cell behavior and are using RNA-Seq to identify genes differentially expressed in BST-2-expressing and BST-2-suppressed cancer cells. Current projects in the Lab focus on:
i. The mechanisms by which BST-2 promotes cancer cell motility and survival.
ii. Characterizing differentially expressed genes identified by RNA-seq analysis and probing their role in BST-2 mediated cancer development and progression.