Research

microRNAs as biomarkers of cancer development and progression

Numerous studies have demonstrated that aberrant expression of specific microRNAs (miRNAs) are involved in many cancer types including colorectal cancer (CRC) and leukemia. Our laboratory seeks to:

  1. Identify miRNA differentially expressed between normal tissue, primary tumor and liver metastasis in order to identify miRNA that could be useful as biomarkers for CRC monitoring and screening in cancer patients. We are particularly interested in dissecting the functional role of miR-182, which is highly expressed in CRC compared to normal colon mucosa.
  2. The role of miRNAs downstream NOTCH1 signaling have been partially elucidated, however their role is not completely clear. Since aberrant NOTCH1 pathway activation is present in numerous hematological tumors, including chronic lymphocytic leukemia and T-cell acute lymphoblastic leukemia (T-ALL), the understanding of the molecular mechanisms downstream of NOTCH1 signaling is fundamental to design novel therapeutic strategies. Our laboratory is currently studying novel miRNAs downstream of NOTCH1 and their roles in NOTCH1-dependent leukemia.
  3. NOTCH1 signaling has been implicated in regulating metabolism both in normal T-cells and in T-cell leukemia. In fact, NOTCH1 inhibition promotes a significant down-regulation of several genes (and possibly miRNAs) involved in regulation of anabolic pathways, including amino acid and nucleotide metabolism, ribosome biogenesis, and protein biosynthesis. The role of some metabolic pathways in T-ALL remains to be defined or further clarified, such as the NOTCH1-MYC-BCAT1. We are investigating the role of BCAT1 and Branched Chain Amino Acid metabolism in T-ALL in order to established whether BCAT1 metabolism could represent a novel therapeutic target.

5 Publications

Grassi, Angela, Perilli, Lisa, Albertoni, Laura, Tessarollo, Sofia, Mescoli, Claudia, Urso, Emanuele D. L., Fassan, Matteo, Rugge, Massimo, Zanovello, Paola (2018). A coordinate deregulation of microRNAs expressed in mucosa adjacent to tumor predicts relapse after resection in localized colon cancer. MOLECULAR CANCER, vol. 17, ISSN: 1476-4598, doi: 10.1186/s12943-018-0770-8

Piovan, Erich, Tosello, Valeria, Amadori, Alberto, Zanovello, Paola (2018). Chemotactic Cues for NOTCH1-Dependent Leukemia. FRONTIERS IN IMMUNOLOGY, vol. 9, ISSN: 1664-3224, doi: 10.3389/fimmu.2018.00633

Turrini Riccardo, Merlo Anna, Martorelli Debora, Faè Damiana Antonia, Sommaggio Roberta, Montagner Isabella Monia, Barbieri Vito, Marin Oriano, Zanovello Paola, Dolcetti Riccardo, Rosato Antonio (2017). A BARF1-specific mAb as a new immunotherapeutic tool for the management of EBV-related tumors. ONCOIMMUNOLOGY, vol. 6, e1304338, ISSN: 2162-4011, doi: 10.1080/2162402X.2017.1304338

Bordin, Fulvio, Piovan, Erich, Masiero, Elena, Ambesi-Impiombato, Alberto, Minuzzo, Sonia, Bertorelle, Roberta, Sacchetto, Valeria, Pilotto, Giorgia, Basso, Giuseppe, Zanovello, Paola, Amadori, Alberto, Tosello, Valeria (2017). WT1 loss attenuates the TP53-induced DNA damage response in T-cell acute lymphoblastic leukemia. HAEMATOLOGICA, ISSN: 0390-6078, doi: 10.3324/haematol.2017.170431

Marigo Ilaria, Zilio Serena, Desantis Giacomo, Mlecnik Bernhard, Agnellini Andrielly, Ugel Stefano, Sasso Maria Stella, Qualls Joseph E, Kratochvill Franz, Zanovello Paola, Molon Barbara, Ries Carola, Runza Valeria, Hoves Sabine, Bilocq Amélie, Bindea Gabriela, Mazza Emilia M. C, Bicciato Silvio, Galon Jérôme, Murray Peter J, Bronte Vincenzo (2016). T Cell Cancer Therapy Requires CD40-CD40L Activation of Tumor Necrosis Factor and Inducible Nitric-Oxide-Synthase-Producing Dendritic Cells. CANCER CELL, vol. 30, p. 377-390-377, ISSN: 1535-6108, doi: 10.1016/j.ccell.2016.08.004

Funding  

Progetto di Ateneo

People involved:

Paola Zanovello
Erich Piovan RC
Alberto Amadori PO

Group members

Valeria Tosello (IOV), Angela Grassi (IOV), Lisa PerilliPost Doc.