I work on three areas: 1) molecular interactions between viruses and the host cells; 2) transport between the cell cytoplasm and the nucleus and 3) transmissible cancers. I have made seminal contributions in each of these fields.

I studied poorly understood events occurring after a retrovirus enters a target cell such as viral capsid uncoating and nuclear transport of the viral complex (J. Virol. 1999, 2001, 2003; EMBO J. 2003). We discovered critical differences between oncoretroviruses and HIV-1, which illuminated their different biology and tropism. We provided the first demonstration that the HIV-1 capsid protein enters into the nucleus and affects integration of the viral genome (PLoS Pathog. 2011). We showed that HIV-1 preferentially integrates within, or near, genes for T cell activation and metabolism to link viral gene expression to the activated or resting state of target CD4+ T cells (PLoS Pathog. 2017). Using chemical genetic approaches, we discovered that host cell factor Hsp90 is critical for HIV-1 gene expression and reactivation from latency (JBC 2010, PLoS Pathog. 2012, PNAS 2014).

By studying tRNAs that are selectively incorporated into HIV-1 particles, we found that, contrary to dogma, tRNAs are re-imported into the nucleus in human cells by an active pathway (PLoS Biol. 2006). This pathway, conserved from yeast to human, is now called "tRNA retrograde transport". It may control cell metabolism by sequestering tRNAs into the nucleus. HIV-1 exploits this pathway to gain access to the nucleus (PLoS Biol;. 2006, PLoS Pathog. 2011).
In collaboration with Bart Hoogenboom (UCL Centre for Nanotechnology), we described the biophysical properties of the native nuclear pore complex using atomic force microscopy thus addressing one of the fundamental problems in cell biology with key implications to understand how viruses travel across the nuclear envelope (Nature Nanotech 2015).

We demonstrated the clonal origin of the canine transmissible venereal tumour, proving that a mammalian cell can evolve into a transmissible cancer cell "parasite" (Cell 2006, Science 2014). CTVT often regresses after treatment with the drug vincristine. We found that CTVT regression depends on an acute inflammation of the host cells surrounding the tumour and upregulation of chemokine CCL5, which attracts and retains immune cells into the tumour site. Thus CTVT has provided fundamental insights into the pivotal role of innate immunity in breaking tolerance to this cancer, which might be applicable to cancer regression in general (Cancer Cell 2018).