I have three main areas of interest: 1) molecular host-virus interactions; 2) nucleocytoplasmic trafficking of viruses and tRNAs; 3) Transmissible cancers.

I investigated poorly understood steps of retrovirus infection such as uncoating and intracellular reverse transcription. I discovered that HIV-1 must shed the capsid core early to progress to productive infection, in contrast to oncoretroviruses. Recently I proposed that, although HIV-1 uncoating starts early, it is completed inside the nucleus and that HIV-1 capsid in the nucleus is important for integration.

I worked on nuclear transport of HIV-1, a step essential for infection of relevant target cells. I devised an in vitro system to study host cell components important for viral nuclear transport and, in collaboration with Dirk Gorlich, discovered that the nuclear import receptor importin 7 promotes HIV-1 nuclear import. My lab discovered that importin 7 also promotes nuclear import of DNA in general, including mitochondrial DNA.

By studying HIV-1 nuclear import my lab discovered that cellular tRNAs are transported back into the nucleus of human cells in an energy dependent way. This new cellular pathway (now called “retrograde tRNA transport”) is conserved from yeast to humans and it is thought to control cell metabolism by modulating tRNA availability in the cytoplasm. We found that HIV-1 evolved to exploit this pathway to enter the nuclei of infected cells.

With Bart Hoogenboom at the UCL Centre for Nanotechnology we are investigating the biophysical properties of the nuclear pore complex (NPC) using polymer physics to better understand the fundamental mechanisms for nuclear import of viruses.

I have set up a high-throughput screening facility in the cat3 lab to investigate host-pathogen interactions by chemical genetics. Chemical genetics is an approach whereby small molecules are first screened to find “hits” with the desired phenotype and then the hit molecule is used as a tool to identify the target. Using this platform, we have found that Hsp90 is required for HIV-1 gene expression and reactivation from latency. We have also identified a molecule that inhibits HIV-1 integration by targeting the capsid protein. We collaborate with the pharmaceutical industry to identify new targets and small molecules capable of blocking HIV-1 infection or delaying AIDS.

I have contributed to the demonstration that the canine transmissible venereal tumour (CTVT) has a clonal origin and is a cancer transmitted as a cellular parasite. I am collaborating with Michael Stratton and Liz Murchison at the Sanger Institute and Stephan Beck at UCL to understand the genetic and epigenetic mechanisms leading to CTVT regression as a general model for cancer regression.