PHD PROGRAMME
 

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.

  

Bibliography 

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