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CANCER RESEARCH U.K.
VIRAL ONCOLOGY GROUP

Viral Oncology

Dimitrios Lagos PhD
Marie Malcles PhD
Mark Cannon MD
Juan Funes PhD
Richard Vart PhD Student

Kaposi’s sarcoma-associated herpesvirus (KSHV) is causally linked to the development of several malignancies, including Kaposi’s sarcoma (KS), the most common cancer in HIV-1 infected individuals, as well as some lymphoproliferative disorders (Figure 3).

We are investigating mechanisms by which KSHV interferes with its cellular environment to protect cells from host immunity and to induce transformation.

KSHV has pirated from the host genome many genes involved in angiogenesis, apoptosis and cell proliferation and immunity. These included viral encoded cyclin, GPCR, IL-6, bcl2 and chemokine homologues. We are employing both global (gene expression microarray and genetic screens) and reductionist methodologies to elucidate the roles which these viral genes play during tumorigenesis.

vGPCR is a constitutively active homologue of the IL-8 receptor, transforms fibroblasts, prolongs endothelial cell growth and induces KS-like tumours in transgenic mice. Mark Cannon is studying signalling cascades initiated by vGPCR, and how these could affect the viral latent-lytic switch. Juanma Funes and Richard Vart are investigating viral genes involved in transformation, endothelial reprogramming and cytokine induction.

We are also studying the global effect of KSHV on the cellular immunome and on the ubiquitin-proteasome system (UPS). The UPS contributes to the regulation of essential cellular processes, such as cell cycle progression, apoptosis and proliferation. Moreover, in tumour cells, accelerated proteolysis contributes to malignant transformation, through a rapid turn-over of tumour suppressors. We have shown that KSHV deregulates important components of the UPS, both at the mRNA and protein levels. Marie Malcles is identifying which viral genes are involved in these particular deregulations and their relevant mechanisms. Dimitrios Lagos investigates how KSHV effects dendritic cell maturation and global effects on the immunome (collaboration, Frances Gotch, IC).

To facilitate these studies we are generating various unique tools, including a lentiviral library encoding all KSHV genes, and a custom made chip array with Affymetrix encoding all oncogenic viral open reading frames, as well as cellular genes involved in viral induced malignancies).


Selected publications

Academic Career

Funding

 


Wolfson Institute for Biomedical Research - The Cruciform Building - University College London
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