Cellular processes are regulated through post-translational modification of proteins. Proteins can be modified through covalent attachment of ubiquitin, or ubiquitination. Research in our lab is focused on the role of ubiquitin and ubiquitin-like proteins in viral infection and cancer.
Current projects
Viruses hijack the host cell by manipulating the fuction and stability of host and viral proteins with the end goal of survival and transmission of the viral genome. We are currently studying the function of ubiquitin and ubiquitin-like proteins in the transition from latency to lytic replication in Kaposi’s sarcoma herpesvirus (HHV-8). The major lytic inducer, RTA, is reported to have intrinsic ubiquitin ligase activity as well as interact with members of the ubiquitin proteasome system. We have found that RTA promotes the degradation of the latently expressed protein vFLIP (Ehrlich 2014) through the cellular Itch ubiquitin ligase (Chmura 2016). We are interested in further characterizing the mechanism behind this activity, as well as identifying additional targets of RTA.
Cul5 is an E3 ubiquitin ligase that is frequently hijacked by viruses. Cul5 has been co-opted by HIV, Adenovirus, KSHV, and HPV. We have previously reported a cellular function of Cul5 in regulation of Hsp90 client proteins (Ehrlich 2009). Hsp90 clients are frequently dysregulated in cancer; in fact Hsp90 is required to maintain the oncogenic state of multiple types of cancer cells. We are interested in exploring the role of Cul5 expression in cancer diagnosis, prognosis and sensitivity to chemotherapy.