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Italo Tempera, PhD

 

Italo Tempera, PhD

 

Assistant Professor, Fels Institute for Cancer Research and Molecular Biology

Assistant Professor, Microbiology and Immunology

Telephone:  215-707-1941

Email: tempera@temple.edu

 

Department of Microbiology and Immunology

Fels Institute for Cancer Research and Molecular Biology

 

Educational Background:

 

BS, Molecular Biology, University of Rome "La Sapienza", Rome, Italy, 2003

 

PhD, Biochemistry, University of Rome "La Sapienza", Rome, Italy, 2007

 

Visiting Scientist, The Wistar Institute, Philadelphia, PA, 2007-2010

 

Postdoctoral Fellowship, The Wistar Institute, Philadelphia, PA, 2010-2012

 

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Research Interests:

 

  • Chromatin architecture and its implication in gene expression
  • Alteration of the three-dimensional structure of chromatin in cancer
  • Relationship between EBV chromosome structure and the carcinogenic risk of EBV infection
  • Identification of cellular and viral proteins involved in chromatin organization
  • Effect of post-translational modifications of CTCF and the Cohesin complex on chromatin architecture
  • Correlation between metabolism and chromosome conformation

Dr. Tempera’s research focuses on understanding the functional links between epigenetic domains, chromosome conformation and gene expression in the contest of cancer. Chromatin composition and organization represent an important element in regulating genome function. The analysis of chromosome conformation in yeast and Drosophila promoted the view of the genome as a set of physical domains that correlate with the epigenetic domains, suggesting a strong link between genome structure and genome function.

Our goal is to understand how the chromatin three-dimensional structure affects gene expression and how cancer can alter this process.

 

In particular we study the role of epigenetic modifications into the mechanism regulating Epstein-Barr virus (EBV) latency since EBV latent infection has been causally linked to a variety of B-cell and epithelial malignancies. EBV is able to establish a life-long latent infection persisting in memory B-lymphocytes as a chromatin-associated multicopy mini-chromosome adopting different gene expression programs that are referred to as latency types. These different latency types are epigenetically stable and correspond to different promoter utilization and depend on the host cell type and the nature of the tumor from which EBV is isolated. Hence, EBV represents a useful system for gaining a new insight into the basic understanding of the role of chromatin architecture in gene expression regulation in mammals. EBV studies are also instrumental in clarifying how cancer manipulates the epigenome for continued neoplastic growth and adaptability.

 

Figure 9_IT.tif

 

Chromatin architecture and its implication in gene expression. Recent studies have implicated CTCF in the regulation of high-order chromatin structure. In particular CTCF has been shown to promote and maintain the formation of intra- and inter-chromosomal interactions between different regions of DNA. Furthermore, genome-wide studies mapping CTCF binding profiles on human genome revealed that CTCF colocalized with Cohesin complex. We aim to clarify the importance of CTCF/Cohesin interaction for the chromatin architecture organization and gene expression by analyzing this association on EBV chromosome as well as on the human genome.

 

Alteration of the three-dimensional structure of chromatin in cancer. An interesting and novel direction that we want to further investigate is the possibility that viruses have evolved to interfere with the mechanisms that regulate chromatin architecture and exploit them to promote and support viral infection. Our research aims to address the question if EBV can manipulate the host chromatin structure to hijack host gene expression and its consequence on carcinogenic risk associated with EBV infection.

 

Correlation between metabolism and chromosome conformation. Another question that interests our lab is how gene expression responds to changes in the cellular environment. We speculate that, as post-translation modifications of histones are critical for chromatin functions, post-translation modifications of proteins involved in chromatin structure are important for remodeling the three-dimensional organization of the genome. CTCF is a critical factor for the chromatin architecture and it is also subject to different post-translation modifications that are very sensible to changes in the metabolic state of the cell. We intend to use EBV as model to reveal the function of post-translation modifications on CTCF. Our project aims to discover the molecular mechanism that translates fluctuations on metabolites into stable change in chromatin structure. This information will offer a new paradigm for understanding how the epigenome responds to environmental stimuli. By clarifying the effect of post-translation modifications on EBV viral expression we can also provide a new potential therapeutic approach for treating EBV infection and EBV-related malignancies.


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PUBMED PUBLICATIONS :


Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

24918163. Plasschaert RN, Vigneau S, Tempera I, Gupta R, Maksimoska J, Everett L, Davuluri R, Marmorstein R, Lieberman PM, Schultz D, Hannenhalli S, Bartolomei MS, CTCF binding site sequence differences are associated with unique regulatory and functional trends during embryonic stem cell differentiation. Nucleic Acids Res 42:11(7487)2014

24468737. Tempera I, Lieberman PM, Epigenetic regulation of EBV persistence and oncogenesis. Semin Cancer Biol 26:(22-9)2014 Jun

24460791. Lu F, Tempera I, Lee HT, Dewispelaere K, Lieberman PM, EBNA1 binding and epigenetic regulation of gastrokine tumor suppressor genes in gastric carcinoma cells. Virol J 11:(12)2014 Jan 24

24257606. Chen HS, Martin KA, Lu F, Lupey LN, Mueller JM, Lieberman PM, Tempera I, Epigenetic deregulation of the LMP1/LMP2 locus of Epstein-Barr virus by mutation of a single CTCF-cohesin binding site. J Virol 88:3(1703-13)2014 Feb

24121688. Plasschaert RN, Vigneau S, Tempera I, Gupta R, Maksimoska J, Everett L, Davuluri R, Mamorstein R, Lieberman PM, Schultz D, Hannenhalli S, Bartolomei MS, CTCF binding site sequence differences are associated with unique regulatory and functional trends during embryonic stem cell differentiation. Nucleic Acids Res 42:2(774-89)2014 Jan

24086258. Martire S, Fuso A, Rotili D, Tempera I, Giordano C, De Zottis I, Muzi A, Vernole P, Graziani G, Lococo E, Faraldi M, Maras B, Scarpa S, Mosca L, d'Erme M, PARP-1 modulates amyloid beta peptide-induced neuronal damage. PLoS One 8:9(e72169)2013

23549386. Arvey A, Tempera I, Lieberman PM, Interpreting the Epstein-Barr Virus (EBV) epigenome using high-throughput data. Viruses 5:4(1042-54)2013 Apr 2

22901543. Arvey A, Tempera I, Tsai K, Chen HS, Tikhmyanova N, Klichinsky M, Leslie C, Lieberman PM, An atlas of the Epstein-Barr virus transcriptome and epigenome reveals host-virus regulatory interactions. Cell Host Microbe 12:2(233-45)2012 Aug 16

21829357. Tempera I, Klichinsky M, Lieberman PM, EBV latency types adopt alternative chromatin conformations. PLoS Pathog 7:7(e1002180)2011 Jul

21365766. Mosca L, Rotili D, Tempera I, Masci A, Fontana M, Chiaraluce R, Mastromarino P, d'Erme M, Mai A, Biological effects of MC2050, a quinazoline-based PARP-1 inhibitor, in human neuroblastoma and EBV-positive Burkitt's lymphoma cells. ChemMedChem 6:4(606-11)2011 Apr 4

20730088. Tempera I, Wiedmer A, Dheekollu J, Lieberman PM, CTCF prevents the epigenetic drift of EBV latency promoter Qp. PLoS Pathog 6:8(e1001048)2010 Aug 12

20219917. Tempera I, Deng Z, Atanasiu C, Chen CJ, D'Erme M, Lieberman PM, Regulation of Epstein-Barr virus OriP replication by poly(ADP-ribose) polymerase 1. J Virol 84:10(4988-97)2010 May

19853673. Tempera I, Lieberman PM, Chromatin organization of gammaherpesvirus latent genomes. Biochim Biophys Acta 1799:3-4(236-45)2010 Mar-Apr

18261989. Tempera I, Buchetti B, Lococo E, Gradini R, Mastronardi A, Mascellino MT, Sale P, Mosca L, d'Erme M, Lenti L, GD3 nuclear localization after apoptosis induction in HUT-78 cells. Biochem Biophys Res Commun 368:3(495-500)2008 Apr 11

17931416. Mattiussi S, Tempera I, Matusali G, Mearini G, Lenti L, Fratarcangeli S, Mosca L, D'Erme M, Mattia E, Inhibition of Poly(ADP-ribose)polymerase impairs Epstein Barr Virus lytic cycle progression. Infect Agent Cancer 2:(18)2007 Oct 11

17929313. Mosca L, Tempera I, Lendaro E, Di Francesco L, d'Erme M, Characterization of catechol-thioether-induced apoptosis in human SH-SY5Y neuroblastoma cells. J Neurosci Res 86:4(954-60)2008 Mar

15895395. Tempera I, Cipriani R, Campagna G, Mancini P, Gatti A, Guidobaldi L, Pantellini F, Mandosi E, Sensi M, Quesada P, Mario UD, D'Erme M, Morano S, Poly(ADP-ribose)polymerase activity is reduced in circulating mononuclear cells from type 2 diabetic patients. J Cell Physiol 205:3(387-92)2005 Dec

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FUNDING:

 

NIH Pathway to Independence (PI) Award K99/R00, NIAID 2012-2015
Role: Principal Investigator.
Project title: Regulation of EBV Latency by Chromosome Conformation

 

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