Research activities of the BMGB Unit within the PhD Programme in Biology, Human Genetics, Bioinformatics: Cellular and Molecular Bases of Phenotype
The characterization of the cellular and molecular bases of Cancer and Degenerative Diseases is a key objective of the Research Unit of Molecular BioMedicine, Genetics, Computational Biology (BMGB). In particular, the models most recently used for the analysis of neoplastic processes have been: (1) Neuroblastoma (NB); (2) Acute Myeloid Leukemia (AML); (3) ColoRectal Carcinoma (CRC); (4) Glioblastoma Multiforme (GBM). As model for studying degenerative disease, we analyzed (5) Diabetes Mellitus (DM). In the near future, we plan to extend our studies to (6) Alzheimer's disease (AD).
(1A) The characterization of the genomics and transcriptomics of the Transcription Apparatus in Homo sapiens (Genomics: 1994a, 1994b; Cytogenetics and Cell Genetics: 1995, 1996, 2000; Oncogene: 1998, 2001; Somatic Cell and Molecular Genetics: 1999; DNA and Cell Biology: 2007) allowed us to use the candidate gene approach to test the involvement of GTFs (General Transcription Factors) in NB pathogenesis and to demonstrate the specific involvement of GTF genes NC2b, TAF12, TAF13. The statistical evidence on the involvement of NC2b is strong: this is particularly interesting considering the role of NC2b in the repression of transcription of eukaryotic genes of all classes and in the negative modulation of cell proliferation (Molecular Cancer: 2008 ).
(1B) Other research, performed as part of our PhD program, demonstrated the important role of three microRNAs (MIR152, MIR200B, MIR338) in the pathogenesis of NB (Journal of Molecular Medicine: 2010).
(2). The Omic characterization of the apoptotic machinery (AM) (BMC Medical Genomics: 2009) has made it possible to verify and confirm the hypothesis that AM genes might be involved in the resistance of some AML patients to chemotherapeutic treatment (BMC Cancer: 2010) .
(3) The study of the alterations of the microRNA expression profile after in vitro cetuximab treatment has allowed the identification of specific molecular profiles, related to the positive or negative response of CRC patients to treatment (Molecular Cancer Therapeutics: 2010). It seems logical to suggest that the continuation of this research should allow the identification of the underlying genotypes and the activation of effective clinical strategies.
(4) We recently identified a microRNA gene, whose coding sequence precisely overlaps to a coding exon of a class II gene encoding a protein. The characterization of the structure of this microRNA gene and its expression dysregulation in GBM are almost completed.
(5) In another research project, we have verified the involvement of both AM and microRNA genes in the pathogenesis of DM by analyzing the alterations of AM and miRNA transcriptome in murine pancreas a and b cells, treated with cytokines. These experiments have allowed to characterize the molecular bases of the higher resistance to cytokines of a cells respect to b cells. Moreover, new candidate genes for involvement in DM etiopathogenesis were identified; we also confirmed DM candidates already known in the literature.
(6) Our studies on the molecular bases of female infertility allowed the identification and characterization of the causal involvement of both GTF and AM genes.
- M Purrello, C Di Pietro, E Mirabile, A Rapisarda, R Rimini, A Tinè, L Pavone, S Motta, K H Grzeschik, G Sichel. Physical mapping at 6q27 of the locus for the TATA-box binding protein, the DNA-binding subunit of TFIID and a component of SL1 and TFIIIB, strongly suggests that it is single copy in the human genome. Genomics 22: 94-100 (1994). IF: 5.136 – Cit (up to 2010): 12.
- M Purrello, C Di Pietro, A Rapisarda, S Motta, K H Grzeschik, G Sichel. Localization of the human genes encoding the two subunits of general transcription factor TFIIE. Genomics 23: 253-255 (1994). IF: 5.136 – Cit (up to 2010): 4.
- M Purrello, C Di Pietro, A Rapisarda, E Mirabile, S Motta, G Sichel, K H Grzeschik. Genetic characterization of general transcription factors TFIIF and TFIIB of Homo sapiens sapiens. Cytogenetics and Cell Genetics 69: 75- 80 (1995). IF: 3.502 – Cit (up to 2010): 4.
- M Purrello, C Di Pietro, A Rapisarda, A Viola, C Corsaro, S Motta, K H Grzeschik, G Sichel. Genomic localization of the human gene encoding Dr1, a negative modulator of transcription of class II and class III genes. Cytogenetics and Cell Genetics 75: 186-189 (1996). IF: 3.636 – Cit (up to 2010): 4.
- M Purrello, C Di Pietro, A Viola, A Rapisarda, S Stevens, M Guermah, Y Tao, C Bonaiuto, A Arcidiacono, A Messina, G Sichel, KH Grzeschik, R Roeder. Genomics and transcription analysis of human TFIID. Oncogene 16: 1633-1638 (1998). IF: 6.192 – Cit (up to 2010): 17.
- C Di Pietro, A Rapisarda, C Bonaiuto, MN Lizzio, H Engel, V Amico, M Scalia, A Amato, KH Grzeschik, G Sichel, M Purrello. Genomics of the human genes encoding four TAFII subunits of TFIID, the three subunits of TFIIA, as well as CDK8 and SURB7. Somatic Cellular and Molecular Genetics 25: 185-189 (1999). IF: 0.944. Cit (up to 2010): 2.
- C Di Pietro, A Rapisarda, V Amico, C Bonaiuto, A Viola, M Scalia, S Motta, A Amato, H Engel, A Messina, G Sichel, KH Grzeschik, M Purrello. Genomic localization of the human genes TAFIA, TAFIB and TAFIC, encoding TAFI48, TAFI63 and TAFI110, subunits of class I general transcription initiation factor SL1. Cytogenetics and Cell Genetics 89: 133-136 (2000). IF: 1.878 – Cit (up to 2010): 1.
- M Purrello, C Di Pietro, A Rapisarda, V Amico, V Giunta, H Engel, S Stevens, Y Hsieh, M Teichman, Z Wang, G Sichel, R Roeder, KH Grzeschik. Genes for human general transcription initiation factors TFIIIB, TFIIIB-Associated Proteins, TFIIIC2, and PTF / SNAPC: functional and positional candidates for tumour predisposition or inherited genetic diseases? Oncogene20: 4877- 4883 (2001). IF: 6.737 – Cit (up to 2010): 6.
- S Piro, G Patanè, C Di Pietro, MN Lizzio, AM Rabuazzo, M Anello, R Vigneri, M Purrello, F Purrello. Exposure to FFA or to high levels of glucose increases apoptosis in rat pancreatic islets cells. Metabolism 51: 1340-1347 (2002). IF: 2.009 – Cit (up to 2010): 67.
- C Di Pietro, V Di Pietro, G Emmanuele, A Ferro, T Maugeri, E Modica, G Pigola, A Pulvirenti, M Purrello, M Ragusa, M Scalia, D Shasha, S Travali, V Zimmitti.ANTICLUSTAL: multiple sequence alignment by antipole clustering and linear approximate 1-median computation. In: Proceedings of the IEEE Bioinformatics Conference, CSB 2003, pp 326-336, August 11-14, Standford, California, USA (2003).
- C Di Pietro, A Ferro, G Pigola, A Pulvirenti, M Purrello, M Ragusa, D Shasha. ANTICLUSTAL: multiple sequence alignment by Antipole clustering. In: Data Mining in Bioinformatics, pp 43-57. Ed Wang, Zaki, Toivonen, Shasha. Sprinter Verlag, London, England (2004).
- C Di Pietro, S Piro, G Tabbì, M Ragusa, V Di Pietro, V Zimmitti, F Cuda, M Anello, U Consoli, E Trovato Salinaro, M Caruso, C Vancheri, N Crimi, MG Sabini, GAP Cirrone, L Raffaele, G Privitera, A Pulvirenti, R Giugno, A Ferro, G Cuttone, S Lo Nigro, R Purrello, F Purrello, M Purrello. Cellular and molecular effects of protons: apoptosis induction and potential implications for cancer therapy. Apoptosis 11: 57- 66 (2006). Published online December 2005. Doi: 10.1007/s10495-005-3346-1. IF: 4.497 – Cit (up to 2010): 12.
- A Ferro, R Giugno, G Pigola, A Pulvirenti, C Di Pietro, M Purrello, M Ragusa. Sequence similarity is more relevant than species specificity in probabilistic backtranslation. BMC Bioinformatics 8: 58 (2007). Doi: 10.1186/1471-2105-8-58. IF: 3.780 – Cit (up to 2010): 2. Accesses (up to august 12th 2010): 1812.
- C Di Pietro, M Ragusa, L Duro, MR Guglielmino, D Barbagallo, A Carnemolla, A Laganà, P Buffa, R Angelica, A Rinaldi, MS Calafato, I Milicia, C Caserta, R Giugno, A Pulvirenti, V Giunta, A Rapisarda, V Di Pietro, A Grillo, A Messina, A Ferro, KH Grzeschik, M Purrello. Genomics, evolution and expression of TBPL2, a member of the TBP family. DNA and Cell Biology 26: 369-385 (2007). Doi: 10.1089/dna.2006.0527. IF: 1.861 – Cit (up to 2010): 2.
- C Di Pietro, M Vento, M Ragusa, D Barbagallo, MR Guglielmino, T Maniscalchi, LR Duro, L Tomasello, P Borzì, P Scollo, M Purrello. TAF4B Is a molecular marker of oocyte quality. In: International Proceedings of 14th World Congress on IVF & 3rd World Congress on IVM, Montreal, September 15-19, 2007. Editors: S Lin Tan, V Gomel, R Gosden, T Tulandi.
- M Purrello. La BioInformatica, uno strumento analitico essenziale nella BioMedicina contemporanea. In: Biologia e Genetica. Coordinatori: G De Leo, E Ginelli, S Fasano, Edises, Napoli (2008).
- C Di Pietro, M Ragusa, D Barbagallo, LR Duro, MR Guglielmino, A Majorana, V Giunta, A Rapisarda, E Tricarichi, M Miceli, R Angelica, A Grillo, B Banelli, I Defferari, S Forte, A Laganà, C Bosco, R Giugno, A Pulvirenti, A Ferro, KH Grzeschik, A Di Cataldo, G Tonini, M Romani, M Purrello.Involvement of GTA protein NC2b in neuroblastoma pathogenesis suggests that it physiologically participates in the regulation of cell proliferation. Molecular Cancer 7: 52 (6 June 2008). Doi: 10.1186/1476-4598-7-52. IF: 5.360 - Cit (up to 2010): 1 - Accesses (up to august 12th , 2010): 1975.
- C Di Pietro, M Vento, M Ragusa, D Barbagallo, MR Guglielmino, T Maniscalchi, L Duro, L Tomasello, P Borzì, P Scollo, M Purrello. Analysis of gene expression in single human oocytes: search for molecular markers related to oocytes quality. Reproductive BioMedicine Online 17: 338-349 (http://www.rbmonline.com/Article/3322, e-pub ahead of print on July 21, 2008). Doi: 10.1016/S1472-6483(10)60217-9. IF: 3.206 – Cit (up to 2010) : 1.
- C Di Pietro*, M Ragusa*, D Barbagallo, LR Duro, MR Guglielmino, A Majorana, R Angelica, S Pernagallo, S Valenti, V D’Agostino, P Triberio, I Tandurella, L Statello, L Tomasello, G Palumbo, P La Cava, G Li Destri, S Lanzafame, V Cafiso, T Bertuccio, M Santagati, F Di Raimondo, S Stefani, B Mishra, M Purrello.The Apoptotic Machinery as a biological Complex System: analysis of its Omics, identification of candidate genes for fourteen major types of cancer, experimental validation in CML and Neuroblastoma. BMC Medical Genomics 2:20 (2009). * = equal contribution. Highly Accessed. Doi: 10.1186/1755-8794-2-20. IF: 2.660 – Cit (up to 2010): 2 - Accesses (up to august 12th 2010): 3113.
- C Di Pietro, M Vento, MR Guglielmino, P Borzì, M Santonocito, M Ragusa, D Barbagallo, LR Duro, A Majorana, A De Palma, MR Garofalo, M Minutolo, P Scollo, M Purrello. Molecular profiling of human oocytes after vitrification strongly suggests that they are biologically comparable to freshly isolated gametes. Fertility and Sterility 94: 2804-2807; e-pub ahead of print on June 8, 2010 (2010). Doi: 10.1016/j.fertnstert.2010.04.060. IF: 4.167.
- M Ragusa, A Majorana, B Banelli, D Barbagallo, MR Guglielmino, LR Duro, R Angelica, L Statello, I Casciano, L Salito, M Scalia, G Magro, C Di Pietro, M Romani, M Purrello. MIR 152, MIR 200B, MIR 338, positional and functional Neuroblastoma candidates, are involved in neuroblast differentiation and apoptosis. Journal of Molecular Medicine 88: 1041-1053 (2010). Highlighted in Cover. Doi: 10.1007/s00109-010-0643-0. IF : 5.004.
- M Ragusa, G Avola, R Angelica, D Barbagallo, MR Guglielmino, LR Duro, A Majorana, L Statello, L Salito, C Consoli, MG Camuglia, C Di Pietro, G Milone, M Purrello. Expression profile and specific network features of the Apoptotic Machinery explain relapse of Acute Myeloid Leukemia after chemotherapy. BMC Cancer 10: 377 (2010). Doi: 10.1186/1471-2407-10-377. IF: 2.740 -Accesses (up to august 12th , 2010): 552.
- M Ragusa, A Majorana, L Statello, M Maugeri, L Salito, D Barbagallo, MR Guglielmino, LR Duro, R Angelica, R Caltabiano, A Biondi, M De Vita, G Privitera, M Scalia, A Cappellani, E Vasquez, S Lanzafame, F Basile, C Di Pietro, M Purrello. Specific alterations of microRNA transcriptome and global network structure in colorectal carcinoma after cetuximab treatment.Molecular Cancer Therapeutics: 9:3396-3409. Doi: 10.1158/1535-7163. MCT-10-0137 (2010). IF: 4.953. Cit (up to 2010) : 1.