Tel. +358 9 191 59445
Fax. +358 9 191 59366
e-mail: paivi dot ojala-at-helsinki dot fi
Institute of Biotechnology
P.O.Box. 56, 00014 University of Helsinki
Street address: Viikinkaari 9, Biocenter 1
Viral tumorigenesis group
About the research
KSHV infection is the causative agent in three different tumor types; Kaposi's sarcoma (KS), a plasmablastic variant of multicentric Castelman's disease and an AIDS-related form of B cell lymphoproliferative disorder called primary effusion lymphoma (PEL). While the mechanisms involved in the pathogenesis are not fully understood, it is intriguing that the KSHV genome contains several potential oncogenes pirated from the human genome. All tumor cells are latently infected by KSHV and express latent genes such as viral cyclin (v-cyclin), vFLIP, the latent nuclear antigen (LANA-1), and the viral interferon regulatory factor 3 (vIRF3). Interestingly, KSHV was recently identified to also encode for 12 viral micro-RNAs (miRNAs), most of them during the latency. The association of KSHV with a human neoplasm and the large number of cellular counterparts in the KSHV genome make it of tremendous interest to determine which of its genes are contributing to its pathogenicity, and which pathways are activated in the host cell upon KSHV tumorigenesis.
Our research group recently discovered a novel viral oncogenesis mechanism by showing that Kaposi sarcoma herpesvirus (KSHV) induces transcriptional reprogramming of primary lymphatic endothelial cells (LECs) to invasive, mesenchymal cells via endothelial-to-mesenchymal transition (EndMT; Cheng et al., Cell Host & Microbe, 2011). EndMT is a process resembling epithelial to mesenchymal transition (EMT) with a proposed role in tumor progression and metastasis. Our recent finding on KSHV-EndMT demonstrates surprising LEC plasticity beyond the endothelial fate. It also underscores the power of human tumor virus research in revealing novel pathways of cancer development. Our current research aims at dissecting the novel cellular circuits involved in reprogramming of LECs and addressing the role of reprogramming in Kaposi sarcomagenesis. We are also interested in continuing our previous work to deepen the understanding of the regulation of the two KSHV replication programs, the latent and lytic replication phases. Moreover, the discovery of virus-induced EndMT has motivated us to hypothesize that LEC reprogramming could be involved also in other human cancers.
The interdisciplinary research program of my group has the potential to make fundamental contributions to the fields of cancer biology and virus-host cell interactions. Our work can open exciting new avenues for efficient therapeutic targeting of the lymphatic system in human pathologies. Our experience in the viral oncogenesis field and in translational, preclinical studies on restoration of p53 function as a novel therapeutic modality for KSHV-lymphomas (Sarek et al., J Clin Invest 2007 & Sarek et al., Oncogene 2012) together with the state-of-the-art research tools and 3D cell models provide an excellent platform and high potential to successfully complete our ambitious research objectives.
Page updated January 25, 2013