UCL Cancer Institute

Cancer Research UK Viral Oncology Group


Group Leader: Professor Chris Boshoff







Our laboratory studies how viruses cause cancer. In particular, we study Kaposi sarcoma herpesvirus (KSHV) and its role in the development of Kaposi sarcoma and lymphoma.


Research

KSHV is linked to the development of Kaposi sarcoma and certain lymphoproliferations, including primary effusion lymphoma and multicentric Castleman’s disease. Kaposi sarcoma is an excellent model to study endothelial cell biology, differentiation and transformation. We also use KSHV to study mechanisms which oncogenic viruses employ to evade host immunity, and to induce cell proliferation and differentiation. In addition, we exploit viral oncogenes like SV40T and HPV E6/E7, to study aspects of tumour metabolism and transformation.

Kaposi Sarcoma Herpesvirus: New Perspectives

Fig 1   Putative pathways of endothelial-cell and Kaposi's sarcoma spindle-cell differentiation (from Nature Reviews Cancer, 2002)



We use molecular and cellular biology techniques to study KSHV and cellular transformation. Our laboratory has significant expertise in lentiviral systems, bioinformatics, miRNA and shRNA technologies, expression arrays and primary human endothelial and tumour cell culture.

Proposed model

Fig 2   Proposed mechanism of KSHV-induced sarcoma (from Nature Reviews Cancer, 2010)



 

Group Members


  • Gemma Bridge, PhD student
  • Laila Cancian, PhD
  • Emanuela Cuomo PhD
  • Rachel Kaufman, PhD student
  • Tim Fenton, PhD
  • Juan Manuel Funes, PhD
  • Ohad Yogev PhD
  • Hiroko Yaguchi, PhD
  • Fiona Gratrix, BSc
  • Stephen Henderson, PhD
  • Leonid Nikitenko, PhD
  • Nirali Patel, BSC

 



 

Selected Publications


KSHV-encoded miRNAs Target MAF to Induce Endothelial Cell Reprogramming. Hansen A, Henderson S, Lagos D, Nikitenko N, Coulter E, Roberts S, Gratrix F, Plaisance K, Renne R, Bower M, Kellam P, Boshoff C. Genes Dev. 2010 Jan 15;24(2):195-205. Pubmed

miR-132 regulates antiviral innate immunity through suppression of the p300 transcriptional co-activator. Lagos D, Pollara G, Henderson S, Gratrix F, Fabani M, Milne RS, Gotch F, Boshoff C. Nature Cell Biol. 2010 May;12(5):513-9. Epub 2010 Apr 25. Pubmed

KSHV manipulates Notch signaling by DLL4 and JAG1 to alter cell cycle genes in lymphatic endothelia.
Emuss V, Lagos D, Pizzey A, Gratrix F, Henderson SR, Boshoff C.
PLoS Pathog. 2009 Oct;5(10):e1000616. Epub 2009 Oct 9. Pubmed

Genomics screen in transformed stem cells reveals RNASEH2A, PPAP2C, and ADARB1 as putative anticancer drug targets. Flanagan JM, Funes JM, Henderson S, Wild L, Carey N, Boshoff C. Mol Cancer Ther. 2009 Jan;8(1):249-60. Pubmed

Toll-like receptor 4 mediates innate immunity to Kaposi sarcoma herpesvirus. Lagos D, Vart RJ, Gratrix F, Westrop SJ, Emuss V, Wong PP, Robey R, Imami N, Bower M, Gotch F, Boshoff C. Cell Host Microbe. 2008 Nov 13;4(5):470-83. Pubmed

Crystal structure of a vFlip-IKKgamma complex: insights into viral activation of the IKK signalosome. Bagnéris C, Ageichik AV, Cronin N, Wallace B, Collins M, Boshoff C, Waksman G, Barrett T. Molecular Cell. 2008 Jun 6;30(5):620-31. Pubmed

Kaposi's sarcoma-associated herpesvirus-encoded interleukin-6 and G-protein-coupled receptor regulate angiopoietin-2 expression in lymphatic endothelial cells. Vart RJ, Nikitenko LL, Lagos D, Trotter MW, Cannon M, Bourboulia D, Gratrix F, Takeuchi Y, Boshoff C. Cancer Res. 2007 May 1;67(9):4042-51. Pubmed