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.
Field(s) of expertise
Past research from the Mastroberardino lab established a connection between age-related defects in DNA repair and Parkinson’s disease (PD); 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.
- Milanese, C., Gabriels, S., Barnhoorn, S., Cerri, S., Ulusoy, A., Gornati, S.V., Wallace, D.F., Blandini, F., Di Monte, D.A., Subramaniam, V.N., Mastroberardino, P.G. Gender biased neuroprotective effect of Transferrin Receptor 2 deletion in multiple models of Parkinson’s disease (2021) Cell Death and Differentiation. DOI: 10.1038/s41418-020-00698-4
- Milanese, C., Bombardieri, C.R., Sepe, S., Barnhoorn, S., Payán-Goméz, C., Caruso, D., Audano, M., Pedretti, S., Vermeij, W.P., Brandt, R.M.C., Gyenis, A., Wamelink, M.M., de Wit, A.S., Janssens, R.C., Leen, R., van Kuilenburg, A.B.P., Mitro, N., Hoeijmakers, J.H.J., Mastroberardino, P.G. DNA damage and transcription stress cause ATP-mediated redesign of metabolism and potentiation of anti-oxidant buffering (2019) Nature Communications, 10 (1), art. no. 4887. DOI: 10.1038/s41467-019-12640-5
- Milanese, C., Mastroberardino, P.G. A perspective on DNA damage-induced potentiation of the pentose phosphate shunt and reductive stress in chemoresistance. (2020) Molecular and Cellular Oncology, 7 (3), art. no. 1733383. DOI: 10.1080/23723556.2020.1733383
- Milanese, C., Payán-Gómez, C., Mastroberardino, P.G. Cysteine oxidation and redox signaling in dopaminergic neurons physiology and in Parkinson's disease. (2019) Current Opinion in Physiology, 9, pp. 73-78. DOI: 10.1016/j.cophys.2019.04.025
- Milanese, C., Payán-Gómez, C., Galvani, M., González, N.M., Tresini, M., Abdellah, S.N., van Roon-Mom, W.M.C., Figini, S., Marinus, J., van Hilten, J.J., Mastroberardino, P.G. Peripheral mitochondrial function correlates with clinical severity in idiopathic Parkinson’s disease. (2019) Movement Disorders, 34 (8), pp. 1192-1202. DOI: 10.1002/mds.27723
- Milanese, C., Cerri, S., Ulusoy, A., Gornati, S.V., Plat, A., Gabriels, S., Blandini, F., Di Monte, D.A., Hoeijmakers, J.H., Mastroberardino, P.G. Activation of the DNA damage response in vivo in synucleinopathy models of Parkinson’s disease. (2018) Cell Death and Disease, 9 (8), art. no. 818. DOI: 10.1038/s41419-018-0848-7
- Milanese, C., Tapias, V., Gabriels, S., Cerri, S., Levandis, G., Blandini, F., Tresini, M., Shiva, S., Greenamyre, J.T., Gladwin, M.T., Mastroberardino, P.G. Mitochondrial Complex i Reversible S-Nitrosation Improves Bioenergetics and Is Protective in Parkinson's Disease. (2018) Antioxidants and Redox Signaling, 28 (1), pp. 44-61. DOI: 10.1089/ars.2017.6992
- Sepe, S., Milanese, C., Gabriels, S., Derks, K.W.J., Payan-Gomez, C., van IJcken, W.F.J., Rijksen, Y.M.A., Nigg, A.L., Moreno, S., Cerri, S., Blandini, F., Hoeijmakers, J.H.J., Mastroberardino, P.G. Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson's Disease. (2016) Cell Reports, 15 (9), pp. 1866-1875. DOI: 10.1016/j.celrep.2016.04.071
- Sepe, S., Payan-Gomez, C., Milanese, C., Hoeijmakers, J.H., Mastroberardino, P.G. Nucleotide excision repair in chronic neurodegenerative diseases. (2013) DNA Repair, 12 (8), pp. 568-577. DOI: 10.1016/j.dnarep.2013.04.009
- Horowitz, M.P., Milanese, C., Di Maio, R., Hu, X., Montero, L.M., Sanders, L.H., Tapias, V., Sepe, S., Van Cappellen, W.A., Burton, E.A., Greenamyre, J.T., Mastroberardino, P.G. Single-cell redox imaging demonstrates a distinctive response of dopaminergic neurons to oxidative insults. (2011) Antioxidants and Redox Signaling, 15 (4), pp. 855-871. DOI: 10.1089/ars.2010.3629