Endocytosis, the process by which cells internalize cargo from the outside, is a tightly regulated process: normal regulation ensures cell functioning while disorganization contributes to cancer progression. This process, far from being a simple one-way route, involves multiple means of internalization that coexist and can operate simultaneously. At the 2022 International Symposium on Chemical Biology, Prof. Sarah Sigismund aims to unravel how endocytic pathways are integrated to regulate receptor signaling in cell physiology and cancer.
Pro. Sarah is Sigismund Dedicated his research career to protein trafficking, In particular, her long-term goal is to uncover the mechanisms by which epidermal growth factor receptor (EGFR) is internalized and how this process may be regulated during the course of disease. EGFR is one of several receptors whose internalization is important for the pathways that control cell differentiation, proliferation and migration. Although, The temporal and spatial regulation of EGFR internalization is complex, EGFR can regulate signaling differently depending on whether it is post-translationally modified, can be activated by both ligand-independent or ligand-dependent mechanisms, and it can be activated by clathrin-mediated Endocytosis (CME) or nonclathrin can enter cells through both endocytosis. NCE) (Giangreko, Malabarba and Sigismund, Biol Cell, 2021).
Early in his career, Prof. Sigismund studied post-translational modifications as a sign of protein endocytosis. She helped show that monoubiquitination – the addition of a single ubiquitin to a protein – is a key signal for EGFR internalization., His research efforts were rewarded with several prestigious awards, including the Cecilia Ciofres Prize, which is assigned to promising young researchers for Italian research on cancer and viral disease.
His research work on the internalization of EGFR also led to Discovery of a novel non-clathrin endocytic (NCE) pathway for EGFR internalization. This endocytic pathway is associated with local Ca. resting on2+ On signaling and the formation of contact sites between the plasma membrane (PM) and the endoplasmic reticulum (ER). This work helped to reinforce the notion that the output of EGFR signaling – attenuation of signaling versus prolonged signaling – also depends on the integration of endocytic pathways and communication between different organelles.
In parallel with his work as Associate Professor, Pro. sigismund Actively involved in promoting science in Italy. She organizes programs and courses and is also a council member and treasurer of the Italian Association for Cell Biology and Differentiation (ABCD), which helps establish networks for students and postdocs, and between the various laboratories in Italy.
During the “Contact Sites Between PM, ER and Mitochondria: Linking EGFR Signaling to Cell Metabolism” at the 2022 International Symposium on Chemical Biology, Prof. Sigismund will discuss the work that led to his discovery of non-clathrin endocytic (NCE). The pathway for EGFR internalization, in particular the molecular mechanisms driving this process and the physiology and functional importance of this pathway for cancer.
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About Sarah Sigismund
Pro. Sarah Sigismund completed her PhD at the Open University (Oxford, UK) and IFOM-IEO, FIRC Institute for Molecular Oncology / European Institute of Oncology (Milan, Italy) under the supervision of Dr. Simona Polo. Following his thesis, titled “Role of remyelination in endocytosis”, he presented Prof. He continued to work on endocytosis as a postdoctoral researcher in the laboratory of Pier Paolo di Fiore, specialist in the field of protein trafficking and director of Endocytosis, Signaling and Cancer. the laboratory. Sara became the head of the endocytosis research team in this lab, whose primary focus is to understand the role of endocytosis in cancer. Today, she is an associate professor at the University of Milan and heads the Endocytosis Research Team. Department of Experimental Oncology, IEO, Milan,