Tcl1 interacts with Atm and enhances NF-κB activation in hematologic malignancies

The T-cell leukemia/lymphoma 1 (TCL1) oncogene is a target of chromosomal translocations and inversions at 14q31.2, and its rearrangements in T cells causes T-cell prolymphocytic leukemias. TCL1 dysregulation in B cells is responsible for the development of an aggressive form of chronic lymphocytic leukemia (CLL), the most common human leukemia. We have investigated the mechanisms underlying the oncogenic functions of Tcl1 protein using  a mass spectrometry approach and have identified Atm (ataxia-telangiectasia mutated) as a candidate Tcl1-interacting protein. The Tcl1-Atm complex formation was validated by coimmunoprecipitation experiments. Importantly, we show that the association of Atm with Tcl1 leads to enhanced lκBα phosphorylation and ubiquitination and subsequent activation of the NF-κB pathway. Our findings reveal functional cross-talk between Atm and Tcl1 and provide evidence for a novel pathway that could be targeted in leukemias and lymphomas. (Blood. 2012; 119(1):180-187)

Dr Gaudio started his career as scientist on September 21st 2001 in the laboratory of Cell Biology, Department of Biological Sciences, at the University of Calabria and He got his Master degree in Biological science from the same university on march 19th 2003. Dr Gaudio defended his thesis entitled: "Role of IGF-1R in the regulation of the intercellular adhesion: modulation of the expression of ZO-1 protein in breast cancer cell lines". After that, he joined the laboratory of Dr Trapasso at the University of Catanzaro (Italy) and successively the group of professor Carlo Croce at The Ohio State University. On December 17th 2009 Dr Gaudio defended his PhD thesis entitled "Fhit interaction with Annexin 4 sensitizes lung cancer cells to paclitaxel" and got his PhD in "Molecular Oncology, Experimental Immunology and Development of Innovative Therapies".

At the Ohio State University, Dr Gaudio spent sever years and he studied site fragile genes such as WWOX and FHIT and published a couple of important papers on these topics. Also, He focused on the role of TCL1 in B-cell lymphomas and his studies were published in the prestigious journal Blood. In collaboration with Dr Trapasso and Dr Paduano at the university of Catanzaro (Italy), he helped to develop the phage display for the identification of PTPRJ agonist peptides. On January 2nd, 2013 Dr Gaudio moved in Switzerland at the Institute of Oncology research, He is responsible for the cell biology and in vivo research activities of the Lymphoma & Genomics Program headed by Dr Bertoni. His works were recently published in important journals, such as Oncotarget, Annals of Oncology and Clinical Cancer Research. Moreover, Dr Gaudio is leading projects of drug discovery based on virtual screening of putative inhibitors of new target of therapy, chemical synthesis of new drugs in collaboration with biotech and pharmacology companies. Dr Gaudio was nominated by the department of the Federal economy (DEFR/SEFRI) of Switzerland on April 4, 2016 as representative of Switzerland and MC member of the COST Action CA15135 "Multitarget paradigm for innovative ligand identification in the drug discovery process" MuTaLig. Moreover, Dr Gaudio was nominated leader of the working group 2 of the same action and so elected member of the committee of management.