Dr Ariberto Fassati

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Personal Profile

Name: Ariberto Fassati Email: a.fassati@ucl.ac.uk
Title: Dr Tel: 020 31082138
Department: Div of Infection & Immunity Fax:
Position: Reader in Cellular & Molecular Virology Address: Wohl Virion Centre, UCL, The Cruciform Building, Gower Street, London, WC1E 6BT
Research Domain: Cancer, Infection, Immunology & Inflammation, Personalised Medicine Web Page:  

Profile

Research Description

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. 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 Transportin 3 is involved in this step.

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, 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) to better understand nuclear import of large cargoes such as viruses.

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. 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.


Research Activities

Humoral immunity to HIV, emerging infections

cellular factors in virus infection

Education Description

I am the Postgraduate Tutor (Research) for the Division of Infection & Immunity. I am in charge of over 90 students registered in the Division and for the admission of new PhD students. I am the director of the PhD programme.

I lecture for the Molecular Virology course (VIRL3001), the Immunology course (IMM2002) and for the MSc in Infection.

UCL Collaborators

Prof Robin Weiss; Prof Stephen Caddick; Dr Yasu Takeuchi; Prof Chris Boshoff

External Collaborators

Publications

    2014

    • Low JS, Fassati A (2014). Hsp90: a chaperone for HIV-1.. Parasitology, 141(9), 1192 - 1202. doi:10.1017/S0031182014000298
    • Anderson I, Low JS, Weston S, Weinberger M, Zhyvoloup A, Labokha AA, Corazza G, Kitson RA, Moody CJ, Marcello A, Fassati A (2014). Heat shock protein 90 controls HIV-1 reactivation from latency.. Proc Natl Acad Sci U S A, , - . doi:10.1073/pnas.1320178111
    • Murchison EP, Wedge DC, Alexandrov LB, Fu B, Martincorena I, Ning Z, Tubio JM, Werner EI, Allen J, De Nardi AB, Donelan EM, Marino G, Fassati A, Campbell PJ, Yang F, Burt A, Weiss RA, Stratton MR (2014). Transmissable dog cancer genome reveals the origin and history of an ancient cell lineage.. Science, 343(6169), 437 - 440. doi:10.1126/science.1247167
    • Maertens GN, Cook NJ, Wang W, Hare S, Gupta SS, Oztop I, Lee K, Pye VE, Cosnefroy O, Snijders AP, Kewalramani VN, Fassati A, Engelman A, Cherepanov P (2014). Structural basis for nuclear import of splicing factors by human Transportin 3.. Proc Natl Acad Sci U S A, , - . doi:10.1073/pnas.1320755111

    2013

    • Labokha AA, Fassati A (2013). Viruses Challenge Selectivity Barrier of Nuclear Pores.. Viruses, 5(10), 2410 - 2423. doi:10.3390/v5102410
    • Berkhout B, Benkirane M, Lever A, Wainberg M, Fassati A, Borrow P, Fujii M, Sriskantharajah S, Cockerill M (2013). Obituary: Kuan-Teh Jeang.. Retrovirology, 10, 28 - . doi:10.1186/1742-4690-10-28
    • Berkhout B, Lever A, Wainberg M, Fassati A, Borrow P, Fujii M (2013). Monsef Benkirane awarded 2013 Ming K. Jeang Foundation Retrovirology Prize: landmark HIV-1 research honoured.. Retrovirology, 10, 38 - . doi:10.1186/1742-4690-10-38
    • Osmanović D, Ford IJ, Hoogenboom BW, Fassati A (2013). Physical modelling of the nuclear pore complex. Soft Matter, 9(44), 10442 - 10451. doi:10.1039/c3sm50722j
    • Dhanoya A, Wang T, Keshavarz-Moore E, Fassati A, Chain BM (2013). Importin-7 mediates nuclear trafficking of DNA in mammalian cells.. Traffic, 14(2), 165 - 175. doi:10.1111/tra.12021

    2012

    • Roesch F, Meziane O, Kula A, Nisole S, Porrot F, Anderson I, Mammano F, Fassati A, Marcello A, Benkirane M, Schwartz O (2012). Hyperthermia Stimulates HIV-1 Replication. PLOS PATHOGENS, 8(7), - . doi:10.1371/journal.ppat
    • Fassati A (2012). Multiple roles of the capsid protein in the early steps of HIV-1 infection.. Virus Res, 170(1-2), 15 - 24. doi:10.1016/j.virusres.2012.09.012

    2011

    • Zhou L, Sokolskaja E, Jolly C, James W, Cowley SA, Fassati A (2011). Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration.. PLoS Pathog, 7(8), e1002194 - . doi:10.1371/journal.ppat.1002194
    • Osmanovic D, Bailey J, Harker AH, Fassati A, Hoogenboom BW, Ford IJ (2011). Bistable collective behavior of polymers tethered in a nanopore. Physical Review E. 85(2012) 061917, , - .

    2010

    • Fassati A (2010). From Duke to King's: Michael Malim wins the 2010 Retrovirology Prize.. Retrovirology, 7, 103 - . doi:10.1186/1742-4690-7-103
    • Vozzolo L, Loh B, Gane PJ, Tribak M, Zhou L, Anderson I, Nyakatura E, Jenner RG, Selwood D, Fassati A (2010). Gyrase B inhibitor impairs HIV-1 replication by targeting Hsp90 and the capsid protein.. J Biol Chem, 285(50), 39314 - 39328. doi:10.1074/jbc.M110.155275
    • Fassati A, Mitchison NA (2010). Testing the theory of immune selection in cancers that break the rules of transplantation.. Cancer Immunol Immunother, 59(5), 643 - 651. doi:10.1007/s00262-009-0809-1
    • Loh B, Vozzolo L, Mok BJ, Lee CC, Fitzmaurice RJ, Caddick S, Fassati A (2010). Inhibition of HIV-1 Replication by Isoxazolidine and Isoxazole Sulfonamides. CHEM BIOL DRUG DES, 75(5), 461 - 474. doi:10.1111/j.1747-0285.2010.00956.x

    2009

    • Zaitseva L, Cherepanov P, Leyens L, Wilson SJ, Rasaiyaah J, Fassati A (2009). HIV-1 exploits importin 7 to maximize nuclear import of its DNA genome.. Retrovirology, 6, 11 - . doi:10.1186/1742-4690-6-11
    • Fassati A (2009). Methods of preparation and analysis of intracellular reverse transcription complexes.. Methods Mol Biol, 485, 107 - 119. doi:10.1007/978-1-59745-170-3_8

    2007

    • Fassati A (2007). Open journals' records to give reviewers their due. Nature, 447(7144), 528 - .

    2006

    • Murgia C, Pritchard JK, Kim SY, Fassati A, Weiss RA (2006). Clonal origin and evolution of a transmissible cancer.. Cell, 126(3), 477 - 487. doi:10.1016/j.cell.2006.05.051
    • Fassati A (2006). HIV infection of non-dividing cells: a divisive problem.. Retrovirology, 3, 74 - . doi:10.1186/1742-4690-3-74
    • Cutiño-Moguel T, Fassati A (2006). A phenotypic recessive, post-entry block in rabbit cells that results in aberrant trafficking of HIV-1.. Traffic, 7(8), 978 - 992. doi:10.1111/j.1600-0854.2006.00449.x
    • Zaitseva L, Myers R, Fassati A (2006). tRNAs promote nuclear import of HIV-1 intracellular reverse transcription complexes. PLoS Biology, 4(10), e332 - . doi:10.1371/journal.pbio.0040332

    2004

    • Bhattacharya B, Weiss RA, Davis C, Holmes H, Hockley D, Fassati A (2004). Detection and quantitation of human immunodeficiency virus type-1 particles by confocal microscopy. J VIROL METHODS, 120(1), 13 - 21. doi:10.1016/j.viromet.2004.03.019

    2003

    • Greber UF, Fassati A (2003). Nuclear import of viral DNA genomes. Traffic, 4(3), 136 - 143.
    • Fassati A, Gorlich D, Harrison I, Zaytseva L, Mingot JM (2003). Nuclear import of HIV-1 intracellular reverse transcription complexes is mediated by importin 7. The EMBO Journal, 22(14), 3675 - 3685. doi:10.1093/emboj/cdg357
    • Nermut NV, Fassati A (2003). Structural analyses of purified human immunodeficiency virus type 1 intracellular reverse transcription complexes. Journal of Virology, 77(15), 8196 - 8206.

    2002

    • Morgan JE, Gross JG, Pagel CN, Beauchamp JR, Fassati A, Thrasher AJ, Di Santo JP, Fisher IB, Shiwen X, Abraham DJ, Partridge TA (2002). Myogenic cell proliferation and generation of a reversible tumorigenic phenotype are triggered by preirradiation of the recipient site. The Journal of Cell Biology, 157(4), 693 - 702. doi:10.1083/jcb.200108047
    • Yuan B, Fassati A, Yueh A, Goff SP (2002). Characterization of Moloney murine leukemia virus p12 mutants blocked during early events of infection. Journal of Virology, 76(21), 10801 - 10810.

    2001

    • Fassati A, Goff SP (2001). Characterization of intracellular reverse transcription complexes of human immunodeficiency virus type 1. Journal of Virology, (8), 3626 - 3635. doi:10.1128/JVI.75.8.3626-3635.2001

    2000

    • Torrente Y, D'Angelo MG, Li Z, Del Bo R, Corti S, Mericskay M, DeLiso A, Fassati A, Paulin D, Comi GP, Scarlato G, Bresolin N (2000). Transplacental injection of somite-derived cells in mdx mouse embryos for the correction of dystrophin deficiency. HUM MOL GENET, 9(12), 1843 - 1852.
    • Usmani B, Fassati A, Dickson G (2000). Development of RNA virus vectors for gene delivery. In Cann A (Ed.), RNA viruses (pp. - ). : Oxford University Press.

    1999

    • Fassati A, Goff SP (1999). Characterization of intracellular reverse transcription complexes of Moloney murine leukemia virus.. J Virol, 73(11), 8919 - 8925.
    • Brown SC, Fassati A, Popplewell L, Page AM, Henry MD, Campbell KP, Dickson G (1999). Dystrophic phenotype induced in vitro by antibody blockade of muscle alpha-dystroglycan-laminin interaction.. J Cell Sci, 112 ( Pt 2), 209 - 216.

    1998

    • Fassati A, Bardoni A, Sironi M, Wells DJ, Bresolin N, Scarlato G, Hatanaka M, Yamaoka S, Dickson G (1998). Insertion of two independent enhancers in the long terminal repeat of a self-inactivating vector results in high-titer retroviral vectors with tissue-specific expression.. Hum Gene Ther, 9(17), 2459 - 2468. doi:10.1089/hum.1998.9.17-2459

    1997

    • Fassati A, Wells DJ, Sgro Serpente PA, Walsh FS, Brown SC, Strong PN, Dickson G (1997). Genetic correction of dystrophin deficiency and skeletal muscle remodeling in adult MDX mouse via transplantation of retroviral producer cells.. J Clin Invest, 100(3), 620 - 628. doi:10.1172/JCI119573
    • Fassati A, Murphy S, Dickson G (1997). Gene therapy of Duchenne muscular dystrophy.. Adv Genet, 35, 117 - 153.

    1996

    • Fassati A, Wells DJ, Walsh FS, Dickson G (1996). Transplantation of retroviral producer cells for in vivo gene transfer into mouse skeletal muscle.. Hum Gene Ther, 7(5), 595 - 602. doi:10.1089/hum.1996.7.5-595

    1995

    • Fassati A, Wells DJ, Walsh FS, Dickson G (1995). Efficiency of in vivo gene transfer using murine retroviral vectors is strain-dependent in mice.. Hum Gene Ther, 6(9), 1177 - 1183. doi:10.1089/hum.1995.6.9-1177
    • Fassati A, Dunckley MG, Dickson G (1995). Retroviral vectors.. Mol Cell Biol Hum Dis Ser, 5, 1 - 19.

    1994

    • Fassati A, Tedeschi S, Bordoni A, Amboni P, Curcio C, Bresolin N, Scarlato G (1994). Rapid direct diagnosis of deletions carriers of Duchenne and Becker muscular dystrophies.. Lancet, 344(8918), 302 - 303.
    • Fassati A, Bordoni A, Amboni P, Fortunato F, Fagiolari G, Bresolin N, Prelle A, Comi G, Scarlato G (1994). Chronic progressive external ophthalmoplegia: a correlative study of quantitative molecular data and histochemical and biochemical profile.. J Neurol Sci, 123(1-2), 140 - 146.
    • Fassati A, Takahara Y, Walsh FS, Dickson G (1994). Production of high titre helper-free recombinant retroviral vectors by lipofection.. Nucleic Acids Res, 22(6), 1117 - 1118.