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Prof Ariberto Fassati
228-B
Division of Infection & Immunity, UCL
The Rayne Building, 5 University Street, London, UK
London
WC1E 6JF
Tel: 020 31087625
Appointment
  • Professor of Cellular & Molecular Virology
  • Div of Infection & Immunity
  • Faculty of Medical Sciences
Role
UCL Department Graduate Tutor for Research,UCL Principal Supervisor,UCL Subsidiary Supervisor
Biography

I graduated in Medicine (Summa cum Laude) at the University of Milan, Italy, and specialised in Neurology in 1994. I moved to the UK and obtained a PhD from King's College (Guy's Hospital), London, in 1997 on gene therapy for neuromuscular diseases and was awarded a Wellcome Trust Prize International fellowship to work with Steve Goff at Columbia University, New York. I returned to the UK in 1999 to work in Robin Weiss's group at UCL, I was awarded a Wellcome Trust Career Development fellowship in 2000 to set up his own group at UCL and a Wellcome Trust University Award in 2004. I am Professor of Cellular & Molecular Virology.

I am also an Associate Editor of Retrovirology, the chair of the Retrovirology prize and have served for many years as a member of the CSS2 board of the Agence National de Recherche sur le SIDA (ANRS) (France).

Research Groups
Research Themes
Research Summary

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 pioneered the study of retroviral capsid uncoating (J. Virol. 1999, 2001, 2003), which to this day is a major topic of research in the field. We provided the first demonstration that the HIV-1 capsid protein enters the nucleus of infected cells and affects integration; we proposed a new step in the HIV-1 life cycle called “nuclear uncoating” (J. Biol. Cem. 2010; PLoS Pathog 2011; Retrovirology 2016). More recently, we found that the capsid protein promotes HIV-1 integration into clusters of functionally related genes that regulate T-cell activation and metabolism (PLoS Pathog. 2017; Sci Rep. 2017). Currently, we are investigating how the 3D organization of chromatin in which HIV-1 has integrated may regulate latency and its reversal. We are also carrying out research to understand why Th17 cells are preferentially infected by HIV-1 and depleted, a key event leading to AIDS pathogenesis.


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). 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". HIV-1 exploits this pathway to gain access to the nucleus (PLoS Biol;. 2006, PLoS Pathog. 2011). We showed that tRNA retrograde transport is part of the response to oxidative stress (Cell Reports 2019).  We are now seeking to map the components of the tRNA retrograde transport pathway and to understand if this pathway affects codon usage by changing the pool of tRNAs in the cytoplasm in response to oxidative stress. Because several viruses induce oxidative stress, we hypothesize that they may induce tRNA retrograde transport to change codon usage to their advantage.


With Robin Weiss, we demonstrated the clonal origin of the canine transmissible venereal tumour (CTVT), proving that a mammalian cell can evolve into a transmissible cancer cell "parasite" (Cell 2006). CTVT often regresses after treatment with the drug vincristine. We found that CTVT regression depends on acute inflammation of the host cells surrounding the tumour and upregulation of chemokine CCL5, which attracts and retains immune cells into the tumour site (Cancer Cell 2018). We are currently investigating how vincristine activates the innate immune system and how it induces CCL5 expression. We are also working to understand how CTVT can bypass allorecognition. We use CTVT as a model to study cancer regression and immunoevasion.

Teaching Summary

I am the Postgraduate Tutor (Research) for the Division of Infection & Immunity. I am in charge of over 50 students registered in the Division and for the admission of new PhD students. I am the director of the PhD programme.

I organise the module "Fundamentals of Cell Biology from a Virus perspective" and give lectures for the Molecular Virology course (VIRL3001), the Immunology course (IMM2002) and for the MSc in Infection.

Academic Background
1997   Doctor of Philosophy United Medical and Dental Schools of Guy's and St.. Thomas's Hospitals
1994   Specialist Universita degli Studi di Milano
1991   Doctor of Medicine Universita degli Studi di Milano
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