Genome instability and metabolism reprogramming in aging

Pier Giorgio Mastroberardino scientific interests revolve around the biology of the nervous system and its alterations in aging and related diseases, for instances neurodegenerative disorders and cancer. He originally investigated the role of cross-linking enzymes in the formation of pathological aggregates in Huntington's disease. Subsequently, his research focus extended to the interplay between two very fundamental aspects of cell biology - metabolism and preservation of the genetic information - in health and disease.

Past research from the Mastroberardino lab established a connection between age-related defects in DNA repair and Parkinson's disease; the team in fact demonstrated that mild impairment of the nucleotide excision repair pathway impacts the dopamine system. This defect induces alterations in mitochondrial physiology and redox homeostasis that parallel those observed in PD, and sensitizes to PD-causing neurotoxins. His team has also unraveled a new mechanism based on allosteric regulation that drives metabolic reprograming following accumulation of transcription-stalling DNA damage – as for instance seen in certain rare genetic diseases or after chemotherapy – by potentiating the pentose phosphate shunt following glycolysis inhibition. The Mastroberardino lab has strong interest in translational research and, for instance, it recently applied artificial intelligence, machine learning algorithms to stratify Parkinson's disease patients on the basis of combined clinical and metabolic variables.

At present, his laboratory continues investigating how crucial factor responsible for neurodegenerative diseases - for instance the aggregating protein alpha-synuclein – contribute to genome instability and metabolic alteration. Additionally, his team keeps exploring the diagnostic potential of machine learning algorithms applied to clinical and molecular/biochemical variables.

Through his joint position between the IFOM and the Erasmus MC in Rotterdam, Pier Giorgio Mastroberardino offers his expertise in metabolism and biology of the nervous system to the larger scientific community in these top institutes and their International partners. The ultimate goal of this combined effort is to catalyze synergies that will open new technological and conceptual avenues in biomedical research.

PhD project title

Alteration in iron metabolism and chelation therapy in Parkinson's disease

14.12.2020 rev. 02