Università degli Studi di Udine

Gianluca TELL

Gianluca TELL

DAME Dipartimento di area medica
Professori Ordinari
BIO/11 Biologia molecolare

Incarichi istituzionali

  • Delegato permanente DAME - Commissione Ricerca Universita' degli Studi di Udine

Attività di ricerca

  • The main focus of my research in the Laboratory of Molecular Biology and DNA repair is focused on understanding the role of Ape1 functions on DNA-repair, Gene expression regulation and on RNA metabolism in cancer cells. Apurinic/apyrimidinic endonuclease 1 (Ape1), an essential protein in mammals, is known to be involved in base excision DNA repair (BER), acting as the major abasic endonuclease; the protein also functions as a redox co-activator of several transcription factors that regulate gene expression. I contributed with seminal papers on the elucidation of the role of Ape1 as a transcriptional coactivator of different transcription factors: Egr-1, p53, NF-B, AP-1, Myb and HIF-1in cancer cells. I made large use of advanced Proteomics and Genomics techniques in my research for the study of different tumor models such as hepatocellular carcinoma. Recent findings obtained by my Lab, highlighted a novel role for Ape1 in RNA metabolism through interaction with NPM1 protein, which is involved in ribosomal processing. Such findings on the role of Ape1 in the post-transcriptional control of gene expression could explain its ability to influence diverse biological processes and its re-localization to cytoplasmic compartments in some tissues and tumors. I recently demonstrated that an altered Ape1/NPM1 interaction is associated with the genomic instability of Acute Myeloid Leukemia cells providing the first basis for a role of a BER impairment in tumor transformation. Recently inhibitors of this interaction have been developed in my Lab, which display antitumor properties. In addition, I proposed that Ape1 may serve as a “cleansing” factor for oxidatively damaged abasic RNA, establishing a novel connection between DNA and RNA surveillance mechanisms. These recent discoveries of the novel functions of Ape1 in controlling RNA metabolism opened up new paradigms that perhaps explain its cytoplasmic distribution, new areas of investigation to define the biological contributions of its multiple functions, and future avenues for translational research. Now, a possible involvement of Ape1 in miRNA metabolism has emerged and is currently under investigation as well as the high-throughput screening for the identification of small molecules able to interfere with this new function of the protein that may have great relevance for tumor biology and novel anticancer therapies.

Gruppi/Unità di ricerca