Signal Transduction Lab | Fondazione Santa Lucia

Signal Transduction Lab

Areas of Investigation 

The Laboratory studies, at the molecular level, the signal transduction mediated by the activity of protein kinases. The deregulation of the expression and activity of these enzymes is associated with the onset of diseases such as cancer and neurodegenerative disorders. We mainly focus our attention on Ataxia Telangiectasia Mutated kinase (ATM), SRC and ABL non-receptor tyrosine kinase, and Receptor Tyrosine Kinases (RTKs).

The Laboratory in particular attempts to identify the molecular mechanisms by which ATM kinase carries out its normal and pathological functions. Loss of ATM expression is linked to the development of Ataxia-Telangiectasia (AT), a rare autosomal recessive genetic disorder characterized by a complex clinical history, including cerebellar neurodegeneration, genomic instability, defects in the immune response and high risk of developing lymphomas and leukemias. ATM is a kinase that plays an essential role in coordinating the response to DNA damage and prevents genomic instability, which causes the onset of tumors. Recent studies identified additional functions that are independent of the response to DNA damage; ATM plays a role in the signal transduction mediated by growth factors and stress, including hypoxia, autophagy and oxidative stress.

 

Role of ATM in Cancer and Neurodegeneration

The Laboratory has identified ATM as a new modulator of apoptosis (programmed cell death), mediated by the stimulation of FAS and TRAIL death receptors. In this regard our studies focus on: 1) the identification of ATM as a new modulator of the E3-ubiquitin ligase ITCH and the analysis of its role in the control of the stability of several ITCH substrates involved in cancer and in cerebellar development and homeostasis; 2) the proteomic analysis of ATM-dependent modulation of protein expression and ubiquitination in lymphoblastoid cell lines derived from AT patients; 3) the identification of ATM as a novel modulator of the response to hypoxia in cancer cells; 4) the characterization of ATM as a novel modulator of the tumorigenicity dependent on HER2 RTK expression in breast cancer and as a possible new prognostic and therapeutic marker of HER2 positive tumors; 5) the characterization of ATM as a modulator of cancer initiating cells and as a novel pharmacological target for the implementation of cancer therapy.

Collaborations 
  • Department of Biology, Tor Vergata University of Rome (Italy)
Ongoing Research Projects 
  • Role of ATM kinase in the signaling cascade modulated by ITCH E3-Ubiquitin Ligase
  • Role of ATM kinase in the modulation of HER2-dependent tumorigenicity
  • Role of ATM kinase as a modulator of cancer initiating cells: a novel for the implementation of cancer therapy.

Laboratory of Signal Transduction

Fondazione Santa Lucia Irccs

Via del Fosso di Fiorano, 64 00143 Rome

European Centre for Brain Research (CERC) – Floor 2 – Rooms 210, 223, 225