Supervisor:
Program of Study:
MSc, Microbiology and Immunology
Project Title:
The PERKs of UPR subversion: Exploring KSHV host-shutoff during lytic replication
Research Summary:
Kaposi’s sarcoma-associated herpesvirus (KSHV) causes two kinds of cancer. We still
have a lot to learn about how this virus changes human cells to cause cancer. As KSHV creates
new viral particles, the virus forces host cells to make lots of viral proteins. Some of these viral
proteins control cell growth and metabolism, whereas others help the virus hide from host cell
immune defences. We discovered that KSHV also turns off cell stress responses that normally
sense and respond to damaged proteins. We have shown that these stress responses are anti-viral
and that shutting them off helps this virus replicate. We recently learned that the virus suppresses
the production of mRNAs that encode stress response proteins. We also identified a viral protein
called ‘K3’ that is at least partly responsible for blocking these stress responses. We are currently
investigating how K3 works, and we are making mutant viruses that lack K3 so we can
determine how this viral protein works in the context of a real infection. Viruses are excellent
teachers and learning how KSHV changes stress responses will bring us closer to understanding
how the virus causes cancer.
Scholarships and/or Awards:
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- BHCRI Cancer Research Training Program (CRTP) Traineeship Award 2022
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- BHCRI Cancer Research Training Program (CRTP) Traineeship Award 2020
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- Dalhousie Medical Research Foundation (DMRF) Genomics in Medicine Graduate Studentship 2020
Career Aspirations:
I am interested in revealing the pro-viral mechanisms elicited by early Kaposi’s sarcoma associated herpesvirus (KSHV) gene products that subvert the hosts unfolded protein response (UPR). KSHV is a well-known oncogenic virus that causes tumorous lesions in an infected, compromised host. For a long time, the KSHV latent lifecycle was the focus of studies regarding how this virus establishes life-long infection in its host, which may give rise to cancer. We now know that the lytic lifecycle is just as important in KSHV tumorigenesis, and I want to address this large research gap, starting with how the virus interacts with our UPR.
Upon graduation from my MSc, I desire to continue to conduct cancer research and make a meaningful contribution to my field. In the McCormick lab I find myself in an immersive and productive research environment and I aim to seek out like places where I can learn and develop my passion for science. Perhaps this journey will lead me to pursue a PhD in Microbiology or working in a research lab.
Location:
Dalhousie University
Publications:
Capo, F., Wilson, A., Di Cara, F. 2019. The intestine of Drosophila melanogaster: a versatile model system to study intestinal epithelial homeostasis and host-microbial interactions in human. Microorganisms. 7, 336; doi:10.3390/microorganisms7090336