University

Elena Santonico is Tenure Track (RTT) Researcher in Molecular Biology at Link Campus University. She graduated with honors in Biological Sciences at the University of Rome Tor Vergata, where she also attained a PhD in Molecular and Cellular Biology. Furthermore, she is qualified as an Associate Professor in the 05/BIOS-08 (Molecular Biology) competition sector. She is also qualified to practise as a biologist.

Her research activity focuses on molecular interactions, with particular attention to the recognition mechanisms between proteins and their role in cell physiology. Cellular functions depend on complex networks of interactions, whose specificity is essential for the correct transmission of signals and for the development of inhibitors in case of alterations. Said research activity begun with a master's degree dissertation at Tor Vergata, studying protein binding domains using phage display, spot synthesis and cell assays; also analysing exposure on lambda phage and variants of the proline-rich region of p53. The specificity of the EH domain of POB1 and other interactions mediated by 14-3-3 proteins, phosphatases and ER-mitochondrial complexes were investigated in depth. The dissertation then focused on membrane receptor trafficking, in particular EGFR endocytosis, regulated by ubiquitination, a key signal that coordinates interaction networks and determines the fate of the receptor. Alterations in these processes can promote tumour progression.

Her main lines of research include:

1) Characterization of protein domain-mediated interactions in the control of EGFR endocytosis. In collaboration with the Weizmann Institute of Science, the mechanisms of internalization mediated by ubiquitination were studied, with particular attention to the VHS and UIM domains, which are responsible for recognizing the ubiquitinated receptor. These studies have helped to clarify the role of ubiquitination signals in the regulation of endocytic traffic. 

2) Analysis of the E3 ligase RNF11 and its role in EGFR regulation. RNF11 is a protein overexpressed in several human tumours, located in early and recycling endosomes. Research has shown that its compartmentalization depends on acylation signals (myristoylation and palmitoylation), which are essential for function and for HECT ligase-mediated ubiquitination (Itch, Nedd4). Alterations in these signals compromise the localization and function of the ligase, affecting intracellular trafficking. Furthermore, RNF11 regulates EGFR downregulation through the inhibition of Itch activity and the recruitment of adaptors such as GGA3. SILAC proteomic analyses have identified new interactors, including the ANKRD13 family, highlighting an EGF-dependent mechanism that influences the lysosomal degradation of the receptor. These studies were conducted in collaboration with international research groups (Germany, Japan, USA). 

3) Study of the specificity of recognition of ubiquitin and NEDD8 binding domains. Ubiquitin binding domains (UBDs) are modular elements that act as effectors downstream of the ubiquitination signal. Among ubiquitin-like proteins, NEDD8 has the highest sequence homology, but with distinct functions. The research led to the identification of new protein domains: • CUBAN, present in the KHNYN protein, with high specificity for NEDD8 and the ability to bind neddylated cullins. Its structure was determined, clarifying the mechanisms of selectivity between ubiquitin and NEDD8. • CoCUN, identified in the N4BP1 protein, specific for ubiquitin and not for NEDD8, with characteristics similar to CUE domains but not evolutionarily related. Both domains are polyubiquitinated in cells, suggesting a role in the regulation of ubiquitination. These studies have contributed to the understanding of the mechanisms regulating receptor trafficking and to the definition of new molecular targets potentially relevant in oncology. The results obtained have led to the filing of patent applications and have opened up new perspectives for the development of targeted therapeutic strategies.

4) Analysis of molecular interaction networks Cellular proteins form interaction networks that are crucial for understanding biological processes under normal and pathological conditions. The construction of these networks requires the extraction and standardization of data from the literature. Curation activities have contributed to the development of important protein interaction databases, including MINT, DOMINO, HuPho and SIGNOR, dedicated respectively to protein-protein interactions, protein-peptide interactions, human phosphatases and biological causal relationships. 

Alongside her research activity, Elena is also heavily involved in teaching activities. Since 2022, she has been teaching the Molecular and Experimental Biology course (9 credits) for the single-cycle Master's Degree in Medicine and Surgery “MedTech” (class LM-41), delivered entirely in English at the Biomedical Campus in Rome. At the same university, she teaches Biology as part of the Foundation Year Programme for international students. From 2016 to 2025, she also taught the supplementary course Mechanisms of Cellular Degradation (2 CFU) for the Master's Degree in Cellular and Molecular Biology and Biomedical Sciences at the University of Rome Tor Vergata.

Curriculum Vitae