Biographical Sketch
Dr. Di Maio is deeply committed to unraveling the intricate mechanisms underlying the pathogenesis of Parkinson’s disease (PD). His research focuses on investigating oxidative stress-related events that contribute to the onset and progression of the disease. By employing innovative techniques and experimental strategies, he aims to generate critical knowledge and tools essential for developing new diagnostic and therapeutic approaches, with the ultimate goal of preventing or treating neurological disorders for the benefit of the broader community.
Recent studies led by Dr. Di Maio have revealed aberrant NADPH Oxidase 2 (NOX2) activation in the post-mortem substantia nigra of PD patients and animal models. This key event is intricately linked to other major PD-related factors, including abnormal LRRK2 kinase activity, α-synuclein modifications, mitochondrial dysfunction, and impaired autophagy. Together, these findings highlight a feedforward cycle that underscores the amplification of NOX2 signaling in PD pathogenesis. Notably, this study provides the first evidence of the significance of neuronal NOX2 activity in idiopathic PD.
Building on these discoveries, ongoing investigations aim to gain a comprehensive understanding of the mechanistic pathways downstream of NOX2 activation. In addition, Dr. Di Maio’s research is exploring innovative therapeutic strategies that involve the downregulation of NOX2 in the nigrostriatal pathway. The research also seeks to evaluate the potential therapeutic benefits of novel multitarget molecules.
Education & Training
- BS, Biomedical Sciences, University of Palermo
- MS, Pharmacology, Consorzio Mario Negri Sud
- PhD, Neuroscience, University Palermo
- Postdoctoral Scholar, University of Pittsburgh
- Research Associate, Neuroscience, University of Pittsburgh
Positions Held
- Assistant Professor, University of Pittsburgh, 7/2023 – Present
- Research Assistant Professor, University of Pittsburgh, 2017 – 2023
Specialized Areas of Clinical, Research and/or Education Interests
A deeper understanding of Parkinson’s disease (PD) pathogenesis is needed for effective treatments. PD is a complex age-related movement disorder, which includes many non-motor symptoms and affects seven to ten million people worldwide. In the United States, the number of PD cases per year is rapidly increasing and it is estimated that by the year 2040 this number will double. Thus, there is an urgent need for novel therapeutic approaches.
PD is a multifactorial disease caused by complex gene/environment interactions. The exact mechanism(s) of the selective nigrostriatal cell loss in PD are still poorly understood. However, there is strong evidence that indicates oxidative stress, aberrant LRRK2 kinase activity, a-synuclein misfolding/aggregation, mitochondrial dysfunction and sustained neuroinflammation are key pathogenic features of PD.
There is a growing consensus that NOX2, a multi-subunit enzymatic complexes that generate reactive oxygen species may play a crucial role in PD-associated nigrostriatal degeneration. Several evidence of altered expression of NOX2 have been reported in the brain of PD patients, indicating that NOX2 may be an important pathogenic event and a potential target in PD therapy.
Professional Organization Membership
- Italian Professional Association of Biologists
- Society for Neuroscience
- American Society for Pharmacology and Experimental Therapeutics (ASPET)
- Mediterranean Society for Neuroscience
Honors & Awards
- Laurea Degree “magna cum laude”, University of Palermo, 10/1991
- Master Scholarship, Consorzio Mario Negri Sud Institute, 1995-1997
Ph.D. Scholarship, European Community & Italian Ministry of University & Research 2001-2005 - Fellowship and Research Grant: Ri.MED Foundation - Italy 2008-2013
- Research Award: “Cannabinoid 1 receptor as therapeutic target in prevention
of chronic epilepsy”; ASPET Conference, Boston – MA 04/2013 - Research Award: “A central role for LRRK2 in idiopathic Parkinson disease”;
PSG Meeting, Portland - OR 10/2016
Selected Recent Publications
1. Horowitz M.P., Milanese C., Di Maio* R., Hu X., Montero L. M., Sanders L.H., Tapias, V., Burton E. A., Greenamyre J. T., and Mastroberardino P.G. (2011) Single- cell redox imaging demonstrates a distinctive response of dopaminergic neurons to oxidative insults. Antioxid. Redox Signal. Aug 15;15 (4):855-71. Jun 6. PMID: 21395478
2. Mullett S.J., Di Maio R, Greenamyre J.T. and Hinkle D.A. (2012) DJ-1 expression modulates astrocyte- mediated protection against neuronal oxidative stress. J. Mol. Neurosci. PMID: 23065353
3. Lee J.W., Tapias V, Di Maio R., Greenamyre J.T., Cannon J.R. (2014) Behavioral, neurochemical and pathologic alterations in bacterial artificial chromosome transgenic G2019S leucine-rich repeated kinase 2 rats. Neurobiol Aging. 2014 Jul 15. PMID: 25174649
4. Di Maio R., Barrett P.J., Hoffman E.K., Barrett C., Zharikov A., Borah A., H u X., McCoy J., C hu C.T., Burton E.A., Hastings .TG. and Greenamyre J.T., (2016) α-Synuclein bnds TOM20 and inhibits mitochondrial protein import in Parkinson’s disease. Sci Transl Med. 2016 Jun 8;8(342):342ra78. doi: 10.1126/scitranslmed. aaf3634. PMID: 27280685
5. Di Maio R., Hoffman EK, Rocha EM, Keeney MT, Sanders LH, De Miranda BR, Zharikov A, Van Laar A, Stepan AF, Lanz TA, Kofler JK, Burton EA, Alessi DR, Hastings TG, Greenamyre JT. (2018) LRRK2 activation in idiopathic Parkinson's disease. Sci Transl Med. 2018 Jul 25;10(451). pii: eaar5429. doi: 10.1126/scitranslmed. aar 5429. PMID: 30045977
6. Rocha EM, De Miranda BR, Castro S, Drolet R, Hatcher NG, Yao L, Smith SM, Keeney MT, Di Maio R, Kofler J, Hastings TG, Greenamyre JT. (2020). LRRK2 inhibition prevents endolysosomal deficits seen in human Parkinson's disease. Neurobiol Dis. 2020 Feb; 134: 104626. doi: 10.1016/j.nbd.2019.104626. Epub 2019 Oct 13. PMID: 31618685
7. Van Laar VS, Chen J, Zharikov AD, Bai Q, Di Maio R, Dukes AA, Hastings TG, Watkins SC, Greenamyre JT, St Croix CM, Burton EA (2020). α-Synuclein amplifies cytoplasmic peroxide flux and oxidative stress provoked by mitochondrial inhibitors in CNS dopaminergic neurons in vivo. Redox Biol. Oct;37: 101695. doi: 10.1016/j. redox. 2020.101695. Epub 2020 Aug 22. PMID: 32905883
8. Keeney MT, Hoffman EK, Greenamyre TJ, Di Maio R (2021). Measurement of LRRK2 Kinase Activity by Proximity Ligation Assay. Bio Protoc. Sep 5;11(17): e4140. doi: 10.21769/ BioProtoc. 4140. eCollection 2021 Sep 5. PMID: 34604446 28.
9. Keeney M.T., Hoffman E.K., Farmer K., Bodle C.R., Fazzari M., Zharikov A., Castro S.L., Hu X., Mortimer A., Kofler J.K., Cifuentes-Pagano E., Pagano P.J., Burton E.A., Hastings T.G., Greenamyre J.T., Di Maio R. (2022). NADPH oxidase 2 activity in Parkinson's disease. S0969-9961(22)00146-2 DOI:
10. Hallacli E, Kayatekin C, Nazeen S, Wang XH, Sheinkopf Z, Sathyakumar S, Sarkar S, Jiang X, Dong X, Di Maio R, Wang W, Keeney MT, Felsky D, Sandoe J, Vahdatshoar A, Udeshi ND, Mani DR, Carr SA, Lindquist S, De Jager PL, Bartel DP, Myers CL, Greenamyre JT, Feany MB, Sunyaev SR, Chung CY, Khurana V. (2022). The Parkinson's disease protein alpha-synuclein is a modulator of processing bodies and mRNA stability. Cell. 2022 Jun 9;185(12):2035-2056.e33. doi: 10.1016/j. cell.2022. 05.008. PMID: 35688132
11. Di Maio R, Keeney MT, Cechova V, Mortimer A, Sekandari A, Rowart P, Greenamyre JT, Freeman BA, Fazzari M. (2023). Neuroprotective actions of a fatty acid nitroalkene in Parkinson's disease. NPJ Parkinson’s Dis. 2023 Apr 7;9(1):55. doi: 10.1038/s41531- 23-00502-3. PMID: 37029127
