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

As a Wellcome Trust International Fellow I joined Stephen Goff’s lab at Columbia University in 1998 and in 2000 moved to UCL with Robin Weiss. Iinvestigated 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.

As a Wellcome Trust Career Development Fellow, 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 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.

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) to better understand nuclear import of viruses and nucleic acids.

With funding from the MRC I have recently set up a high-throughput screening facility in the cat3 lab to investigate host-pathogen interactions by chemical genetics and RNAi. 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. We have identified several compounds targeting novel host cell factors important for HIV-1 replication.  Such new "druggable" antiretroviral targets will be further exploited in collaboration with David Selwood (UCL Medicinal Chemistry) and Steve Caddick (UCL Chemistry).

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.