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The University of Insubria CV
The University of Insubria CV
The University of Insubria CV The University of Insubria CV Roberto S. Accolla
The University of Insubria CV
 

Contact data

Full Professor
Department of Clinical and Biological Sciences
Via Ottorino Rossi, n.9 – 21100 Varese
Tel: +39-0332-217213 / +39-348-3034698
Fax: +39-0332-217219
E-mail: roberto.accolla@uninsubria.it
 

Biography

 Prof. Accolla was born in Augusta (SR) on September 26, 1949. He obtained his MD degree (summa cum laude) from the University of Rome “La Sapienza” in 1974, where he also obtained the post-graduate title of Specialist in Pathology (summa cum laude) in 1977.

From 1975 to the end of 1976 he was post-doctoral fellow in the Department of Pathology, School of Medicine, University of Pennsylvania, directed by Prof. Norman R. Klinman, working on the regulation of immune response by the idiotype-anti-idiotype network. After a year as research fellow at the University of Genova, Italy, in January 1978 he moved to Lausanne, Switzerland, at the Ludwig Institute for Cancer Research where he first became Assistant Member in 1980 and, in 1983, Associate Member. In 1988 he returned to Italy as Associate Professor of Immunology at the University of Verona Medical School. In 1994 he was appointed Full Professor of General Pathology. Since 1995 he is Professor of General Pathology and Immunology at the University of Insubria School of Medicine.
 

Qualifications and awards

 1. Member of the Board of ISTITUTO SUPERIORE DI ONCOLOGIA (I.S.O.), a University consortium (15 Italian Universities) for the basic and clinical advance in cancer research and treatment, under the control of Italian Ministry of Education, University and Research.

2. Advisor and Collaborator of the World Health Organization (WHO) for the Continuous Education Programme in Immunology and Vaccines.

3. Member of the Scientific Board of “Research and Progress Foundation” chaired by Prof. Robert C. Gallo, with the purpose of supporting the development of “Human Resources involved in the Biomedical Research with particular attention to the fields of Infectious Diseases and Oncology.

4. Member of the American Association of Immunologists (AII)

5. Member of OECI (Organization of European Cancer Institutes)

6. Member of GEIE-LINK (European Economic Interest Grouping, named Liaison Network for Cancer)

7. Member of UICC (International Union against Cancer)

8. Member of European Cancer Forum

9. Member of the European Network of Immunological Societies

10. Member of the Società Italiana di Immunologia e Immunologia
Clinica (SIICA)

11. Past Member of the Suisse Society of Biochemistry
 

Research interests

His research interests focus on Immunogenetics and Immunopathology, with special emphasis on the genetic basis of autoimmunity and immunodeficiency and to cancer immunology. He was the first to isolate and describe monoclonal antibodies against the carcinoembryonic antigen (1) which then served for trials of tumor immunolocalization in vivo both in experimental animals and human, and for setting up new ELISA and RIA sandwich assays for CEA detection in patient’s serum samples . He was also deeply involved in the immunological characterization of melanoma antigens (2). In the field of Immunogenetics his major focus was on the structure and regulation of MHC gene expression. He was among the first to biochemically characterize and assess the molecular heterogeneity and polymorphism of the human MHC (HLA) class II molecular pool (3,4). One of his most important achievement was the discovery of the locus AIR-1 encoding the major regulator of MHC class II gene transcription (designated also CIITA, class II transcriptional activator) and the characterization of its function (5-7). This discovery made it possible to genetically and molecularly assess the importance of MHC class II expression in the regulation of the immune response. The possibility to genetically manipulate the AIR-1 gene product was instrumental in showing Professor Accolla’s laboratory that human tumor cells lacking expression of MHC class II genes carry either a developmentally suppressed AIR-1 locus (8), or post-transcriptional modifications of CIITA which make the transactivator inactive for triggering the transcription of MHC-II genes (9,10). Transfection of CIITA into tumor cells restored MHC class II expression and conferred to cells antigen processing and presentation ability in vitro (10). All these findings were the basis for developing the idea that genetically engeneered CIITA-expressing tumor cells, because of newly acquired MHC-II expression, might serve as surrogate APCs for enhanced TAA presentation to CD4+ T cells, the key cells that initiate the anti-tumor response. The basic principles of this approach have received confirmation by his very recent studies (11). At present, his major goal is to characterize the immune response against the CIITA-modified tumor and to demonstrate that the induction of CIITA, at least in certain tumor types, may represent a new tool to increase tumor immunogenicity thus favoring tumor rejection. Importantly, CIITA-modified tumor cells may also be envisaged as a new vaccine strategy to prevent tumor growth in susceptible hosts.

Another important line of investigation has recently focused on the interaction between human retroviruses (HIV-1 and HTLV-2) and infected cells and on the possibility to block viral replication by manipulating host gene expression. Because CIITA and Tat (the HIV-1 viral transactivator) share peculiar similarities in the way they control transcription of their target genes (12), Prof. Accolla and collaborators hypothesized that HIV-1 may be counteracted in cells that upregulate their HLA-II expression. In fact, it was possible to demonstrate that the functional activity of Tat on the viral LTR is greatly inhibited by CIITA (13). More importantly, sustained expression of CIITA in T cell lines resulted in the block of HIV replication after infection (13). A similar role of CIITA has been discovered in the HTLV-2 retroviral infection in which the human transactivator blocks specifically the Tax-2 transactivator (14). This novel CIITA role may represent a new tool for therapeutic strategies aimed at counteracting HIV-1 and HTLV-2 replication and spreading.
Cumulative impact factor (I.F.) up to November 2005: 712,22
 

Teaching experience and appointments

 1984-Present: Teacher at Advanced WHO courses on Immunology, Vaccinology and Biotechnology applied to Infectious Diseases (French and English courses).

1987-1994: Associate Professor of Immunology, Responsible of the Immunology course at the School of Medicine, University of Verona, Italy.

1992-1994: Lecturer in Basic Immunology, Immunochemistry and Immonogenetics, School of Medicine, University of Brescia, Brescia, Italy.

1994-1995: Full Professor of Pathology and Immunology, Responsible of the courses of Cellular and Molecular Pathology and Immunology, Faculty of Sciences, University of L’Aquila, Italy.

1995-present: Full Professor of General Pathology and Immunology,
Responsible for the courses of General Pathology and
Immunology, School of Medicine, University of Insubria, Varese, Italy.

2003-present: Coordinator of the PhD Program in Experimental
Medicine and Oncology

2005: Member of the Evaluation Committee of the University of Insubria
 

Representative  publications

Cited references

1. Accolla, R.S., S.Carrel, and J-P Mach. 1980. Monoclonal 
antibodies specific for carcinoembryonic antigen and produced  by two hybrid cell lines. Proc. Natl. Acad. Sci. USA. 77:563-566. (I.F.:10,789)

2. Carrel, S., R. S. Accolla, A.L.Carmagnola, and J-P Mach. 1980. Common human melanoma associated antigen(s) detected by monoclonal antibodies. Cancer Res. 40:2523-2528. (I.F.: 8,460)

3. Accolla, R.S., N. Gross, S. Carrel, and G.Corte. 1981.  Distinct forms of both a and b subunits are present in the human Ia molecular pool. Proc. Natl.  Acad. Sci. USA, 78:4549-4551. (I.F.: 10,789)

4.  Accolla, R.S. 1984. Analysis of the  structural heterogeneity and polymorphism of  human Ia antigens. Four distinct subsets of molecules are coexpressed in the Ia  pool of both DR 1,1  homozygous and DR  3,W6 heterozygous B cell lines. J. Exp.  Med. 159:378-393. (I.F.: 15,882 )

5.  Accolla, R.S., M. Jotterand-Bellomo, L.Scarpellino, A.Maffei, G.Carra, and J.Guardiola. 1986. aIr-1, a newly found locus on mouse chromosome 16  encoding  a  trans-acting  activator  factor for MHC class II gene expression. J. Exp. Med. 164:369-374. (I.F.: 15,882 )

6. Latron, F.,M.Jotterand-Bellomo, A.Maffei,L. Scarpellino, M. Bernard, J.L. Strominger, and  R.S. Accolla. 1988.  Active suppression of MHC class II  gene  expression  during  differentiation  from  B  cells to plasma cells. Proc. Natl. Acad. Sci. USA, 85:2229-2233 (I.F.: 10,789 )

7. Sartoris, S., M.T. Scupoli, L. Scarpellino, F. Paiola, M. Jotterand- Bellomo, G. Tridente, and R.S. Accolla. 1990. Inducible and constitutive MHC class II gene expression: distinct tissue specific genetic controls. J. Immunol., 145:1960-1967. (I.F.: 7,166)

8. Sartoris, S., G. Tosi, A. De Lerma Barbaro, T. Cestari, and R.S. Accolla. 1996. Active suppression of the class II transactivator-encoding AIR-1 locus is responsible for the lack of major histocompatibility complex class II gene expression observed during differentiation from B cells to plasma cells.  Eur. J. Immunol., 26:2456-2460. (I.F.: 5,438)

9. Sartoris, S., M.T. Valle, A. De Lerma Barbaro, G. Tosi, T. Cestari, A. D’Agostino, A.M. Megiovanni, F. Manca, and R.S. Accolla. 1998.  HLA class II expression in uninducible hepatocarcinoma cells after transfection of AIR-1 gene product CIITA. Acquisition of antigen processing and presentation capacity.  J. Immunol., 161:814-820. (I.F.: 7,014)

10. Croce, M., De Ambrosis, A., Corrias, M.V., Pistoia, V., Occhino, M., Meazza, R., Giron-Michel, J., Azzarone, B., Accolla, R.S., Ferrini, S. 2003. Different levels of control prevent interferon-g-inducible HLA class II expression in human neuroblastoma cells. Oncogene, 22:7848-7857 (I.F.: 6,49)

11. Meazza, R., Comes, A., Orengo, A.M., Ferrini, S., and Accolla, R.S. 2003. Tumor rejection by gene transfer of the MHC class II transactivator in murine mammary adenocarcinoma cells.  Eur. J. Immunol. 33:1183-1192 (I.F.: 5,240)

12.  Accolla, R.S, De Lerma Barbaro A., Mazza S., Casoli C., De Maria A., and Tosi G., 2001. The MHC class II transactivator: prey and hunter in infectious diseases. Trends Immunol.  22:560-563. [I.F.: 15,507)

13.  Accolla, R.S., Mazza, S., De Lerma Barbaro, A., De Maria , A., and Tosi G. 2002. The HLA class II transcriptional activator blocks the function of HIV-1 Tat and inhibits viral replication.  Eur. J. Immunol. 32:2783-2791 (I.F.: 5,240)

14. Casoli, C., De Lerma Barbaro, A., Pilotti, E., Bertazzoni, U., Tosi, G., Accolla, R.S. 2004. The MHC class II transcriptional activator (CIITA) inhibits HTLV-2 viral replication by blocking the function of the viral transactivator Tax-2. Blood, 2004, 103: 995-1001 (I.F.:9,631)

Additional relevant references

15. Scarpa, A., G. Zamboni, A. Achille, P. Capelli, G. Bogina, C. Iacono, G.Serio, and R.S. Accolla. 1994. ras-Family gene mutations in neoplasia of the ampulla of Vater. Int. J. Cancer, 59: 1-4. (I.F.: 3,918)

16. Rigaud, G., F. Paiola, and R.S. Accolla. 1994. In vivo DRA promoter occupancy in MHC class II-negative cells. Eur. J. Immunol.  24: 2415 2420. (I.F.: 5,438)

17. De Lerma Barbaro, A., S. Sartoris, G. Tosi, M. Nicolis and R.S. Accolla. 1994. Evidence for a specific post-transcriptional mechanism controlling expression of HLA-DQ, but not DR and DP, molecules.  J. Immunol. 153:4530-4538. (I.F.: 7,166)

18. Accolla, R.S., L. Adorini, S. Sartoris, F. Sinigaglia, and J. Guardiola. 1995. MHC: orchestrating the immune response.  Immunol. Today  16:8-11. [I.F.: 14,954)

19. Rigaud, G., A. De Lerma Barbaro, M. Nicolis, T. Cestari, D. Ramarli, A-P. Riviera, and R.S. Accolla. 1996. Induction of CIITA and modification of in vivo HLA-DR promoter occupancy in normal thymic epithelial cells treated with IFN-g.  J. Immunol. 156: 4254-4258  (I.F.:7,166)

20. Casoli, C., M.C. Re, P. Monari, G. Furlini, G. Tosi, C. Gradozzi, P.P. Dall’Aglio, U. Bertazzoni, and R.S. Accolla. 1998.  Human HTLV-II virus directly acts on CD34+ hematopoietic precursors by increasing their survival potential. Envelope associated HLA class II molecules reverse this effect. Blood, 91: 2296-2304. (I.F.: 9,631)

21. De Lerma Barbaro, A., G. Tosi, M-T. Valle, A.M. Megiovanni, S. Sartoris, A. D’Agostino, O. Soro, M.C. Mingari, G.W. Canonica, F. Manca, and R.S. Accolla. 1999. Distinct Regulation of HLA class II and class I cell surface expression in THP-1 macrophage cell line after bacterial phagocytosis. Eur. J. Immunol.  29: 499-511. (I.F.: 5,240)

22. Tosi, G., A. De Lerma Barbaro, A. D’Agostino, M.T. Valle, A.M. Megiovanni, F. Manca, A. Caputo, G. Barbanti Brodano, and R.S. Accolla. 2000. HIV-Tat mutants in the cysteine-rich region  down-regulate HLA class II expression in T lymphocytic and macrophage cell lines.  Eur. J. Immunol. 30:19-28. (I.F.: 5,240)

23. Tosi, G., Meazza, R., De Lerma Barbaro, A., D’Agostino, A., Mazza, S., Corradin, G., Albini, A., Noonan, D. M., Ferrini, S., and Accolla R.S., 2000. Highly stable oligomerization forms of HIV-1 tat detected by monoclonal antibodies and requirement of monomeric forms for the transactivating function on the HIV-1 LTR.  Eur. J. Immunol.  30:1120-1126. (I.F.: 5,240)24. De Paulis, A., De Palma R., Di Gioia L., Carfora M., Prevete N., Tosi G., Accolla RS, and Marone G., 2000. Tat protein is an HIV-1 encoded SS-chemochine homolog that promotes migration and upregulates CCR3 on human FceRI+ cells  J. Immunol. 165:7171-7179.  (I.F.: 7,014)

25. De Lerma Barbaro, A., Tosi, G., Frumento, G., Bruschi, E., D’Agostino, A., Valle, M-T., Manca , F., and Accolla R.S.,  2002. Block of Stat-1 activation in macrophages phagocytosing bacteria causes reduced transcription of CIITA and consequent impaired antigen presentation. Eur. J. Immunol. 32:1309-1318 (I.F.: 5,240)

26. Barbanti-Brodano, G., A. Corallini, R.S. Accolla, F. Martini, and M. Tognon. 2004. Re: Lack of serologic evidence for prevalent simian virus 40 infection in humans. J. Natl. Cancer Inst. 96:803-804. (I.F.: 14,5)#

27. De Lerma Barbaro, A., F.A. Procopio,  L. Mortara, G. Tosi, and R.S. Accolla. 2005.  The MHC class II transactivator (CIITA) mRNA stability is critical for the HLA class II gene expression in differentiating myelomonocytic cells. Eur.J.Immunol., 35: 603-611 #(I.F.:5,240).

28. Croce M, Meazza R, Orengo AM, Radic L, De Giovanni B, Gambini C, Carlini B, Pistoia V, Mortara L, Accolla RS, Corrias MV, Ferrini S. 2005. Sequential immunogene therapy with interleukin-12- and interleukin-15-engineered neuroblastoma cells cures metastatic disease in syngeneic mice.  Clin Cancer Res., 15:735-742. (I.F.: 5,991)

29. De Lerma Barbaro, A., G. Frumento, F.A. Procopio, and R.S. Accolla. 2005. MHC immunoevasins: protecting the pathogen reservoir in infection. Tissue Antigens, 66:2-8 (I.F.:2,158)

30. Bettaccini, A, A. Baj, R.S. Accolla, F. Basolo, A. Toniolo. 2005. Proliferative activity of extracellular  HIV-1 Tat protein in human epithelial cells: expression profile of pathogenetically relevant genes. BMC Microbiology  5: 20-33

                                  

 

 
 
   
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