Research

Research Scientist, Center for Dementia Research
Pasquale.DAcunzo@nki.rfmh.org
Research Assistant Professor, Department of Psychiatry, NYU Grossman School of Medicine
D’Acunzo NYU Page
Pasquale.D’acunzo@nyulangone.org
D’Acunzo Lab
Extracellular Vesicles (EVs) are replication-deficient, membrane-bound cellular material constitutively released into the extracellular space by all cell types. Our laboratory recently identified and characterized a novel subpopulation of small brain EVs originating from mitochondria; we named these EVs mitovesicles. Given the novelty of our discovery, the roles of mitovesicles in the regulation of brain mitochondria homeostasis are both unknown and unstudied. In addition, several Alzheimer’s disease (AD)-risk factors (aging, apolipoprotein E genotype, high levels of the amyloid β precursor protein) alter brain mitovesicle biogenesis, content, and secretion, however the functional downstream effects of these changes remain to be determined.
Understanding the physiological and pathological roles of mitovesicles is the current main focus of D’Acunzo’s laboratory. For example, we recently found that mitovesicles isolated from the brain of a mouse model of Down syndrome (DS) contain high levels of a protein (monoaminoxidase B) that regulates the extracellular content of monoaminergic neurotransmitters. Because of this imbalance, DS (but not disomic control) mitovesicles impair long-term potentiation, a molecular mechanism important for memory formation. The study of mitovesicles has particular relevance to neurodegenerative diseases, including AD, because mitochondrial (and, possibly, mitovesicle) dysfunctions are among the earliest pathological alterations in the brain, decades before the onset of clinical symptoms. Given that chronic damage to brain mitochondria induces metabolic alterations, spread of reactive oxygen species, synaptic deficits, and neuronal cell loss, mitochondria and mitochondria-derived EVs arise as attractive targets for therapeutic intervention.
Research Interests
Dr. D’Acunzo is studying the interrelationship between mitochondrial homeostasis and mitovesicles biogenesis, content, and function in the brain, both under physiological and pathological conditions. The ultimate goal of his research is to determine whether and how mitovesicle contribute to pathology spreading in neurodegenerative disorders, in order to develop innovative, mitovesicle-centered targets for therapeutic intervention.
Education
B.Sc. (Medical Biotechnology), University of Milan, Milan, Italy
M.Sc. (Medical Biotechnology), Vita-Salute San Raffaele University, Milan, Italy
Ph.D. (Cell and Molecular Biology), Tor Vergata University, Rome, Italy
Postdoctoral Training
Department of Biology, Cecconi’s laboratory, Bambino Gesù Pediatric Hospital, Rome, Italy
Center for Dementia Research, Levy Lab, Nathan S. Kline Institute and New York University, New York, NY
Awards and Honors
2025 Fowler, et al., 2024, selected for the cover page of Nature Neuroscience (January 2025 Vol. 28 No. 1).
2024 “Lucani Insigni Award” issued by the Regional Council of Basilicata (Italy)
2022 D’Acunzo, et al., 2022 selected as “Featured Paper of the Week” by Nature Protocols
2021 Featured Abstract at the ISEV2021 Annual Meeting, International Society for Extracellular Vesicles
2021 Young Investigator Award, International Society for Extracellular Vesicles
Selected Publications
D’Acunzo P, Pérez-González R, Kim Y, Hargash T, Miller C, Alldred MJ, Erdjument-Bromage H, Penikalapati SC, Pawlik M, Saito M, Saito M, Ginsberg SD, Neubert TA, Goulbourne CN, Levy E. Mitovesicles are a novel population of extracellular vesicles of mitochondrial origin altered in Down syndrome. Sci Adv. 2021 Feb 12;7(7):eabe5085. doi: 10.1126/sciadv.abe5085. PMID: 33579698; PMCID: PMC7880603.
D’Acunzo P, Kim Y, Ungania JM, Pérez-González R, Goulbourne CN, Levy E. Isolation of mitochondria-derived mitovesicles and subpopulations of microvesicles and exosomes from brain tissues. Nat Protoc. 2022 Nov;17(11):2517-2549. doi: 10.1038/s41596-022-00719-1. Epub 2022 Aug 12. PMID: 35962195; PMCID: PMC9633367.
D’Acunzo P, Ungania JM, Kim Y, Barreto BR, DeRosa S, Pawlik M, Canals-Baker S, Erdjument-Bromage H, Hashim A, Goulbourne CN, Neubert TA, Saito M, Sershen H, Levy E. Cocaine perturbs mitovesicle biology in the brain. J Extracell Vesicles. 2023 Jan;12(1):e12301. doi: 10.1002/jev2.12301. PMID: 36691887; PMCID: PMC9871795.
D’Acunzo P, Argyrousi EK, Ungania JM, Kim Y, DeRosa S, Pawlik M, Goulbourne CN, Arancio O, Levy E. Mitovesicles secreted into the extracellular space of brains with mitochondrial dysfunction impair synaptic plasticity. Mol Neurodegener. 2024 Apr 14;19(1):34. doi: 10.1186/s13024-024-00721-z. PMID: 38616258; PMCID: PMC11017499.