Patrizia Caposio, Ph.D.

Biography
Dr. Patrizia Caposio received her B.Sc in Biology from University of Turin, Italy in 1999.  She obtained her Master in Microbiology and Virology in 2004 and the doctorate degree in Biochemistry in 2007 at the Department of Public Health and Microbiology, University of Turin. In the period 2005-2009 she became research assistant professor at the University of Turin. She is currently an assistant scientist at the Vaccine and Gene Therapy Institute, OHSU.

Research overview

The focus of my research is to understand the molecular mechanisms of the interaction between Cytomegalovirus (HCMV) and host cells. In particular the topics I'm interested in are:

1) identify the mechanisms of chronic disease due to HCMV persistent infection: the importance and the interest of HCMV as a pathogen has increased over the past two decades, with the escalation in the number of immunosuppressed patients, either undergoing immunosuppressive therapy following solid organ or bone marrow transplantation. Epidemiological and animal studies have been linked HCMV infection to the development of vascular diseases such as atherosclerosis, restenosis and transplant vascular sclerosis, however the mechanisms involved in this process remain unknown. A growing body of evidence supports a role for angiogenesis and wound healing in the development of vascular disease, for this reason the goal of my laboratory is to understand how the virus induces angiogenesis. In particular we are trying to identify the class of viral gene(s) involved in this process as well as the critical cellular factors secreted from infected cells induced by these gene(s) that induce angiogensis. 

2) establish human cytomegalovirus (HCMV) as a new human vaccine vector platform. Unique characteristics of CMV are: a) ability to re-infect and disseminate through the population regardless of prior CMV immunity b) a capacity to induce high levels of humoral and cellular immune responses against the heterologous pathogen target antigen c) a capacity to maintain these responses essentially for the life of the host d) induction of 'effector memory'-based immunity (T cells localized to mucosal effector sites with immediate effector function) and e) the potential to insert large cassettes in which theoretically over 50kb of the viral genome can be replaced with foreign DNA. A vaccine strategy using a CMV-based vector expressing antigens from different pathogens may be ideally suited for several reasons: it can help us to study the role of the T-cell response in the control of the disease and can re-infect and establish a persistent infection regardless the host CMV immunity.

Grants
PNWRCE Carreer Development Award CD004 "Cytomegalovirus (CMV)-based vaccine for epidemic Chikungunya virus".

Publications
1: Klyushnenkova EN, Kouiavskaia DV, Parkins CJ, Caposio P, Botto S, Alexander RB, Jarvis MA. A cytomegalovirus-based vaccine expressing a single tumor-specific CD8+ T-cell epitope delays tumor growth in a murine model of prostate cancer. J Immunother. 2012 Jun; 35(5): 390-9. PMCID: PMC3366429

2: Tierney R, Nakai T, Parkins CJ, Caposio P, Fairweather NF, Sesardic D, Jarvis MA. A single-dose cytomegalovirus-based vaccine encoding tetanus toxin fragment C induces sustained levels of protective tetanus toxin antibodies in mice. Vaccine. 2012 Apr 26; 30(20): 3047-52. Epub 2012 Mar 10. PubMed PMID: 22414558

3: Umashankar M, Petrucelli A, Cicchini L, Caposio P, Kreklywich CN, Rak M, Bughio F, Goldman DC, Hamlin KL, Nelson JA, Fleming WH, Streblow DN, Goodrum F. A novel human cytomegalovirus locus modulates cell type-specific outcomes of infection. PLoS Pathog. 2011 December; 7(12): e1002444. PMCID: PMC3248471

4: Tsuda Y, Caposio P, Parkins CJ, Botto S, Messaoudi I, Cicin-Sain L, Feldmann H, Jarvis during the past year.  A replicating cytomegalovirus-based vaccine encoding a single Ebola virus nucleoprotein CTL epitope confers protection against Ebola virus.  PLoS Negl Trop Dis. 2011 August; 5(8): e1275.  PMCID: PMC3153429

5: Botto S, Streblow DN, DeFilippis V, White L, Kreklywich CN, Smith PP, Caposio P. IL-6 in human cytomegalovirus secretome promotes angiogenesis and survival of endothelial cells through the stimulation of surviving.  Blood. 2011 January 6; 117(1): 352–361. PMCID: PMC3037756

6: Caposio P, Orloff SL, Streblow DN. The role of cytomegalovirus in angiogenesis.  Virus Res. 2011 May; 157(2): 204–211. PMCID: PMC3040784

7: Caposio P, Luganini A, Bronzini M, Landolfo S, Gribaudo G. The Elk-1 and serum response factor binding sites in the major immediate-early promoter of human cytomegalovirus are required for efficient viral replication in quiescent cells and compensate for inactivation of the NF-κB sites in proliferating cells. J Virol. 2010 May; 84(9): 4481–4493. PMCID: PMC2863749

8: Baggetta R, De Andrea M, Gariano GR, Mondini M, Rittà M, Caposio P, Cappello P, Giovarelli M, Gariglio M, Landolfo S. The interferon-inducible gene IFI16 secretome of endothelial cells drives the early steps of the inflammatory response. Eur J Immunol. 2010 Aug; 40(8): 2182-9. PubMed PMID: 20480502

9: Caposio P, Luganini A, Bronzini M, Landolfo S, Gribaudo G. The Elk-1 and serum response factor binding sites in the major immediate-early promoter of human cytomegalovirus are required for efficient viral replication in quiescent cells and compensate for inactivation of the NF-kappaB sites in proliferating cells. J Virol. 2010 May; 84(9): 4481-93. Epub 2010 Feb 10. PMCID: PMC2863749

10: Caglio R, Valetti F, Caposio P, Gribaudo G, Pessione E, Giunta C. Fine-tuning of catalytic properties of catechol 1,2-dioxygenase by active site tailoring. Chembiochem. 2009 Apr 17; 10(6): 1015-24. PMID: 19301316

11: Luganini A, Caposio P, Landolfo S, Gribaudo G. Phosphorothioate-modified oligodeoxynucleotides inhibit human cytomegalovirus replication by blocking virus entry.  Antimicrob Agents Chemother. 2008 March; 52(3): 1111–1120.  PMCID: PMC2258505

12: Luganini A, Caposio P, Mondini M, Landolfo S, Gribaudo G. New cell-based indicator assays for the detection of human cytomegalovirus infection and screening of inhibitors of viral immediate-early 2 protein activity. J Appl Microbiol. 2008 Dec; 105(6): 1791-801. PMID: 19120629

13: Caposio P, Gugliesi F, Zannetti C, Sponza S, Mondini M, Medico E, Hiscott J, Young HA, Gribaudo G, Gariglio M, Landolfo S. A novel role of the interferon-inducible protein IFI16 as inducer of proinflammatory molecules in endothelial cells. J Biol Chem. 2007 Nov 16; 282(46): 33515-29. PMID: 17699163

14: Caposio P, Luganini A, Hahn G, Landolfo S, Gribaudo G. Activation of the virus-induced IKK/NF-kappaB signalling axis is critical for the replication of human cytomegalovirus in quiescent cells. Cell Microbiol. 2007 Aug; 9(8): 2040-54. PMID: 17419715

15: Fumagalli M, Musso T, Vermi W, Scutera S, Daniele R, Alotto D, Cambieri I, Ostorero A, Gentili F, Caposio P, Zucca M, Sozzani S, Stella M, Castagnoli C. Imbalance between activin A and follistatin drives postburn hypertrophic scar formation in human skin. Exp Dermatol. 2007 Jul; 16(7): 600-10. PMID: 17576240

16: Caposio P, Musso T, Luganini A, Inoue H, Gariglio M, Landolfo S, Gribaudo G. Targeting the NF-kappaB pathway through pharmacological inhibition of IKK2 prevents human cytomegalovirus replication and virus-induced inflammatory response in infected endothelial cells. Antiviral Res. 2007 Mar; 73(3): 175-84. PMID: 17070604

17: Zannetti C, Mondini M, De Andrea M, Caposio P, Hara E, Peters G, Gribaudo G, Gariglio M, Landolfo S. The expression of p16INK4a tumor suppressor is upregulated by human cytomegalovirus infection and required for optimal viral replication. Virology. 2006 May 25; 349(1): 79-86. PMID: 16504234

18: Caposio P, Dreano M, Garotta G, Gribaudo G, Landolfo S. Human cytomegalovirus stimulates cellular IKK2 activity and requires the enzyme for productive replication. J Virol. 2004 March; 78(6): 3190–3195.  PMCID: PMC353729

19: Caposio P, Riera L, Hahn G, Landolfo S, Gribaudo G. Evidence that the human cytomegalovirus 46-kDa UL72 protein is not an active dUTPase but a late protein dispensable for replication in fibroblasts. Virology. 2004 Aug 1; 325(2): 264-76. PMID: 15246266

20: Aimetti M, Romano F, Torta I, Cirillo D, Caposio P, Romagnoli R. Debridement and local application of tetracycline-loaded fibres in the management of persistent periodontitis: results after 12 months. J Clin Periodontol. 2004 Mar; 31(3): 166-72. PMID: 15016019

21: Gribaudo G, Riera L, Caposio P, Maley F, Landolfo S. Human cytomegalovirus requires cellular deoxycytidylate deaminase for replication in quiescent cells. J Gen Virol. 2003 Jun; 84(Pt 6): 1437-41. PMID: 12771412

22: Divari S, Valetti F, Caposio P, Pessione E, Cavaletto M, Griva E, Gribaudo G, Gilardi G, Giunta C. The oxygenase component of phenol hydroxylase from Acinetobacter radioresistens S13. Eur J Biochem. 2003 May; 270(10): 2244-53. PMID: 12752444

23: Caposio P, Torta AI, Romano F, Aimetti M, Romagnoli R, Marchiaro G, Cirillo DM. Molecular approaches to the identification and treatment monitoring of periodontal pathogens. New Microbiol. 2003 Jan; 26(1): 121-4. PMID: 12578320

24: Gribaudo G, Riera L, Rudge TL, Caposio P, Johnson LF, Landolfo S. Human cytomegalovirus infection induces cellular thymidylate synthase gene expression in quiescent fibroblasts. J Gen Virol. 2002 Dec; 83(Pt 12): 2983-93. PMID: 12466474

25: Caposio P, Pessione E, Giuffrida G, Conti A, Landolfo S, Giunta C, Gribaudo G. Cloning and characterization of two catechol 1,2-dioxygenase genes from Acinetobacter radioresistens S13. Res Microbiol. 2002 Mar; 153(2): 69-74. PMID: 11900265

26: Pessione E, Giuffrida MG, Mazzoli R, Caposio P, Landolfo S, Conti A, Giunta C, Gribaudo G. The catechol 1,2 dioxygenase system of Acinetobacter radioresistens: isoenzymes, inductors and gene localisation. Biol Chem. 2001 Aug; 382(8): 1253-61. PMID: 11592407

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