Domenico Frezza
Domenico Frezza
affiliation: Università di Roma Tor Vergata
research area(s): Genetics And Genomics
Course: Cell and Molecular Biology
University/Istitution: Università di Roma Tor Vergata
Education and training :

1968 Graduate from high school (liceo scientifico) Florence, Italy.
1969-1974 University of Pisa. Student for the degree in the faculty of Sciences.
1975 Gratuated with full votation Doctor of Sciences in Genetics at the University of Pisa.

Brief chronology of Employment:

1976-1978 Visiting fellow at N.I.H., Microbial genetic section, Laboratory of Enviromental Mutagenesis, U.S.A.
1979-1980 Research fellow, Laboratory of Genetics, Institute of Marine Biology, Venice
1981-1982 Laboratory of molecular biology, Institute of Biochemestry, University of Padova.
1983-2001 Research staff, Laboratory of Genetics, Department of Biology, University of Tor Vergata, Rome.
1991-2002 Incharge of the course of Advanced Genetic of Microorganisms in the specialization school of Biotechnologies of the University of Tor Vergata
1992-2001 Incharge of the course of Genetic Engeniering for the Biology degree of Science of the University of Tor Vergata
2002 Associate professor of Genetic Engineering for the Biology degree of Science of the University of Tor Vergata
2004 and following years incharged of the following teachings: “Applied Biology” for the triennal curriculum of Human Biology; “Genetic Engineering” for the triennal curriculum of Cellular and Molecular Biology; “Human Genome and genetic diseases” for the biennal specialising degree of Cellular and Molecular Biology.
2009 and following years incharged for the course “Genomic“ for the biennal specialising degree of Industrial Biotechnology.

Scientific background:

Genetic of microorganisms, mutagenesis, validation of new tests of Mutagenesis using Bacteria (Salmonella Arabinose resistance, Histidine mutations) and yeast (S. pombe, adenine mutations, S. cerevisiae gene conversion).
Genetic organization of the yeast mitochondrial genome, regulation of the oxi-3 gene splicing. The role of the first intron encoding an mRNA maturase for its correct splicing.
Mammalian cell regulation. The immortalization of human B lymphocytes by the Epstein-Barr virus, virus-host relationship, the mechanisms of integration of the virus in the human genome; regulation, differential expression in human lymphoblastoid cell lines and thymocytes, analysis of different transcripts of human genes in in B and T lymphocytes in relation to different conditions of growth and stimulation. Genetic analysis of the 3' regulatory region (3’RR) of the cluster of the heavy chain genes of the immunoglobulines.

Present interests

Studies on the structure and frequencies of the polymorphisms of the Ig Heavy chain regulatory Region enhancer complex in different human populations. Analysis of the Haplotypes and polymorphic structure and function of the HS1.2 enhancer 3' to IgH C alpha-1 and C alpha-2 genes. Studies about the structure and role the ORFs mapping at the 3' of both the α (1-2) gene of the costant heavy chain of the immunoglobulines. Possible influence on lymphocyte gene expression of this transcripts and enhancer polymorphisms, studies of the transcription levels by quantitative RT-PCR with real time Light Cycler Roche system. Analysis of B lymphocytes with different alleles of the anhancer HS1,2 in relationship to the B cell induction and stimulations. Gel shift analysis (EMSA) with different lymphocytes extracts and different alleles fragment for the specific binding of transcription factors as NF-kB and SP1. Correlation studies of the allelic frequencies with different immune-diseases (Coeliac disease, Crohn disease, Psoriasis, Systemic Sclerosis, Rheumatoid Arthritis). Population genetic analysis in the different continents and in particular in Italy for a genetic-epidemiologic study on the immune-diseases. Studies on epigenetic transformations and association of polymorphisms to structural chromatine and genomic functions.

D. Frezza, V. Giambra, R.Cianci, M. Giufre', C. Cammarota , C. Martínez-Labarga, A. Fruscalzo, O. Rickards, G. Scibilia, C. Sferlazzas, F. Bartolozzi , G. Magazzù, G.Gasbarrini, F.Pandolfi: Increased frequency of the immunoglobulin enhancer hs1,2 allele 2 in coeliac disease.
Scand. J. Gastroenterol. (2004) 39, 1083-1087.

Vincenzo Giambra, Alberto Fruscalzo, Maria Giufre', Cristina Martinez-Labarga, Marco Favaro, Mariano Rocchi, Domenico Frezza. Evolution of human IgH3’EC duplicated structures: both enhancers HS1, 2 are polymorphic with variation of transcription factor’s consensus sites. Gene (2005) 346: 105-114.

Chiappini B, Brambilla G, Agrimi U, Vaccari G, Aarts HJ, Berben G, Frezza D, Giambra V.
Real-time polymerase chain reaction approach for quantitation of ruminant-specific DNA to indicate a correlation between DNA amount and meat and bone meal heat treatments.
J AOAC Int. (2005) 88: 1399-403.

V. Giambra, C. Martínez-Labarga, M. Giufre', D. Modiano, J. Simpore’, B. K. Gisladottir, R. Francavilla, G. Zhelezova, S. S. Kilic, M. Crawford, G. Biondi, O. Rickards, D. Frezza. Immunoglobulin Enhancer HS1,2 polymorphism: a new powerful anthropogenetic marker. Online Early Pub. Ann. Hum. Genet. (2006) 70: 946-950.

Frezza D, Giambra V, Tolusso B, De Santis M, Bosello S, Vettori S, Triolo G, Valentini G, Ferraccioli G. Polymorphism of immunoglobulin (Ig) enhancer element HS1,2A: allele *2 associates with Systemic Sclerosis. Comparison with HLA-DR and DQ alleles frequency. Ann Rheum Dis. (2007) Mar 28; [Epub ahead of print] 66,1210-5.

Martinez-Labarga C, Lelli R, Tarsi T, Babalini C, De Angelis F, Ottoni C, Giambra V, Pepe G, Azebi E, Frezza D, Biondi G, Rickards O. Polymorphisms of the COL1A2, CYP1A1 and HS1,2 Ig enhancer genes in the Tuaregs from Libya. Ann Hum Biol. (2007) 34, 425-36.

Domenico Frezza, Vincenzo Giambra, Fatima Chegdani, Cecilia Fontana, Giampietro Maccabiani, Nadia Losio, Elena Faggionato, Barbara Chiappini, Gabriele Vaccari, Christoph von Holst, Luigi Lanni, Stefano Saccares and Paolo Ajmone-Marsan. Standard and Light-Cycler PCR Methods for Animal DNA Species Detection in Animal Feedstuffs. Innovative Food Sc. Emerg. Technol. (2008), 9, 18–23.

Cianci R, Giambra V, Mattioli C, Esposito M, Cammarota G, Scibilia G, Magazzù G, Orlando A, Sandri G, Bianchi L, Gasbarrini GB, Pandolfi F, Frezza D.
Increased Frequency of Ig Heavy-Chain HS1,2-A Enhancer *2 Allele in Dermatitis Herpetiformis, Plaque Psoriasis, and Psoriatic Arthritis. J Invest Dermatol. 2008, 128: 1920-4. [IF 5.25]

Gargioli C, Giambra V, Santoni S, Bernardini S, Frezza D, Filoni S, Cannata SM. The lens-regenerating competence in the outer cornea and epidermis of larval Xenopus laevis is related to pax6 expression. J Anat. 2008, 212:612-20. [IF 2.063]

Giambra V, Volpi S, Emelyanov AV, Pflugh D, Bothwell AL, Norio P, Fan Y, Ju Z, Skoultchi AI, Hardy RR, Frezza D, Birshtein BK. Pax5 and linker histone H1 coordinate DNA methylation and histone modifications in the 3' regulatory region of the immunoglobulin heavy chain locus. Mol Cell Biol. 2008, 28, 6123-6133. [IF 5.942]

B Tolusso, D Frezza, C Mattioli, AL Fedele, S Bosello, F Faustini, G Peluso, V Giambra, D.Pietrapertosa, A Morelli, E Gremese, M De Santis, GF Ferraccioli. Allele*2 of the HS1,2A enhancer of the Ig regulatory region associates with Rheumatoid Arthritis. Ann Rheum Dis. 2009, 68:416-9. [IF 7.188]

D. Frezza, V. Giambra1, C. Mattioli, K. Piccoli, R. Massoud, A. Siracusano, M. Di giannantonio, B.K. Birshtein and I.A. Rubino. Allelic frequencies of 3’ ig heavy chain locus enhancer hs1,2-a associated with ig levels in patients with schizophrenia. Int J Immunopathol and Pharmacol. Vol. 22, 115-123 (2009). PMID: 18952640 [IF 2.793]

V. Giambra , R.Cianci, S. Lolli, C.Mattioli, G.Tampella, M. Cattalini, Sebnem S. Kilic, F.Pandolfi, A. Plebani, Domenico Frezza. Allele *1 of HS1.2 Enhancer associates with selective IgA deficiency and IgM concentration. J.Immunol. 15 Dec, vol. 183, 8280-8285, (2009). [IF 6.00]

D'Addabbo P, Scascitelli M, Giambra V, Rocchi M, Frezza D. Position and sequence conservation in Amniota of polymorphic enhancer HS1.2 within the palindrome of IgH 3'Regulatory Region.
BMC Evol Biol. 2011 Mar 15;11(1):71. [IF 4.29 ]

Project Title:
3D structures and functions of the Ig heavy chain 3'Regulatory Region
Three-dimensional (3D) conformation and relative arrangement of chromosomes in the nucleus has a major role in controlling gene-expression programs. Regulatory Regions as LCR perform their activity through different mechanisms by means of secondary structures and epigenetic changes. The mechanisms involved for these 3D remodeling are mediated by consensus sequences of DNA and formation of complexes DNA-protein able to localize specific genomic regions inside nuclear factories (Eskiw et al., C S H Symp Quant Biol 2011, volume 75: 501-506). The Immunoglobulin heavy chain (IgH) 3’ Regulatory Region (3’RR), plays a crucial role in immunoglobulin production and B cell maturation. In humans, there are 2 copies of the 3’RR. Rodents have only one copy of 3’RR with an extra enhancer probably acquired by a rodent–lineage specific duplication event (D’Addabbo et al. BMC Evol Biol. 2011 Mar 15;11:71-83).
To determine the evolutionary conservation and transformation of the main structures of IgH 3’RR we compared the genomic organization in vertebrates. We found that in the 8 species in which the whole genomic region was included in a fully assembled contig (mouse, rat, dog, rabbit, panda, orangutan, chimpanzee, and human), the main elements showed synteny and a highly conserved sequence. The wide 3’RR (»30 Kb in human) bears in all species a large palindromic sequence, consisting in two ~3 Kb complementary branches spaced by a ~3 Kb sequence always including the HS1.2 enhancer. The maintenance of the palindrome was despite an inter-specific divergence at sequence level. Another relevant result concerns human polymorphism of the HS1.2 enhancer, associated to immune diseases in our species. We detected a similar polymorphism in all the studied Catarrhini (a primate parvorder). The polymorphism consists of multiple copies of a 40 bp element, separated by stretches of Cytosine. The number of duplicates is up to 12 in chimpanzees, 8 in baboons, 6 in macaque, 5 in gibbons, and 4 in humans and orangutan. We confirmed specific binding of these elements to nuclear factors. The in silico prediction of “tetraplex” structures in 3’RR enhancers suggested to study in vitro these DNA sequences for the formation of 3D "tetraplex". The analysis includes UV spectroscopy, CD and NMR on HS1.2 polymorphic “Tetraplex” predicted region. The palindrome is retained in evolutionary distant species. It suggests pressures for the maintenance of two self-matching regions driving a hairpin structure. The conservation of the palindromic structure and the primates polymorphic feature of HS1.2 show the relevance of these structures in directing and modulating the Ig production through the formation of three-dimensional organization. The hypothetical “tetraplex” formation and its variability for different alleles of the HS1.2 enhancer is another possible feature confirming the regulatory activity mediated by secondary structures of DNA. The program will include the use of the molecule TMPYP4 to see the differences with the stabilizing effect, to detect other possible secondary structures in vitro.