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• Daniel V. Schidlow, MD, Transformational Leadership Award, 91制片厂 (2023)
• Elected to the National Academy of Inventors (2020)
• Elias Abrutyn Mentoring Award, 91制片厂 (2020)
• NIH-NIDA MERIT Award (Method for Extension of Research in Time) R37-DA15014 (2018-2028)
• Outstanding Service and Support Award, Society on Neuroimmune Pharmacology (2017)
• Basic Research Scientist Award, 91制片厂 (2011)
• Excellence in Research Award, 91制片厂 (2002/03, 2003/04)

Visit the Meucci Lab

Dr. Meucci's laboratory aims to identify therapeutic targets for neurodegenerative and neuroinflammatory disorders and contribute to the development of neuroprotective drugs. Her research efforts over the last two decades have primarily focused on HIV-associated neurocognitive disorders (HAND), with a main interest in the interplay of host, viral and environmental factors in neuropathology. Due to the close link between HIV infection and substance use, the laboratory also investigates how opioids interact with the endogenous chemokine system 鈥� a crucial regulator of both immune and nervous system function.

The Meucci lab has published extensively on chemokine physiopathology in the central nervous system (CNS) and cellular/molecular mechanisms of HIV neuropathogenesis, which has revealed promising therapeutic targets against HAND and other cognitive disorders. These efforts have focused on the chemokine-receptor pairs CXCL12/CXCR4 and CX3CL1/CX3CR1, which are constitutively expressed in the CNS and regulate essential neuronal and glia functions. The lab uses in vitro, ex vivo, and in vivo model systems (i.e., primary neuronal and glial cultures, brain slice cultures, animal models, and human brain specimens) to investigate mechanisms of disease and test potential therapeutic interventions. Additional collaborative projects study chemokines roles in cancer.

Dr. Meucci鈥檚 research has been continuously funded by the NIH and other organizations since 2001, and she recently received the prestigious MERIT award from NIH-NIDA. Her most significant accomplishments have been in the following main areas (see publications tab for more details).

HIV-induced neuronal damage and potential pharmacologic targets for HAND

HIV neuropathology is a complex disorder driven by multiple effects of HIV neurotoxins on different brain cells. HIV fails to infect neurons directly, but Dr. Meucci鈥檚 early work found that neurons can express chemokine receptors like CXCR4, a co-receptor that HIV uses to infect immune cells. HIV proteins can disrupt these neuronal chemokine receptors, which normally promote brain homeostasis. These studies formed a foundation to uncover how CNS chemokine receptors contribute to HAND, and potential therapeutic approaches that target chemokine receptors and related pathways. Our recent work has examined how HIV damages neurons in a new human brain slice culture model of HIV infection.

The lab has also developed new tools and approaches to study how HIV interacts with the aging brain, as people using antiretroviral therapies often live full lifespans. As clinical studies suggest people with HAND can accumulate amyloid-尾 in neurons, we developed unique fusion proteins to precisely control amyloidogenic pathways in a longstanding collaboration with Dr. Renato Brandimarti (University of Bologna). These proteins take advantage of the herpes simplex virus protein US9 to deliver cargo that binds the amyloid precursor protein (APP) in subcellular organelles and diverts APP from amyloidogenic secretases. These molecular tools are helping us uncover how HIV regulates amyloidogenic pathways, and how amyloid processing contributes to HAND during aging.

Chemokine receptors in the CNS

The lab discovered that chemokines regulate a variety of critical functions in differentiated neurons, such as neuronal-glial communication, neurotransmission, and excitotoxicity. These discoveries have helped predict how chemokines contribute to normal and pathological conditions and allowed us to explore new therapeutic approaches to reduce neuroinflammation and neuronal damage in the adult brain. Recent work identified that neuronal CXCR4 signaling helps neurons form new connections within their local network, and this pathway can overcome HIV-induced neuronal disconnection and improve cognitive performance in an animal model of HAND.

The opioid-chemokine interaction in HAND

The lab found that homeostatic CXCR4 signaling is also inhibited by opiates, which revealed unexpected factors that may drive HIV neuropathology in people with substance use disorders. Opioids inhibit CXCR4 via a unique mechanism that dysregulates neuronal iron stores and causes neurons to upregulate ferritin heavy chain, an iron storage protein that also inhibits CXCR4 downstream signals. These studies have opened a new research area on how opioids regulate neuronal iron metabolism, and how iron regulates neuronal structure, function, and homeostasis. This work suggests opioid use may have much larger implications both within and outside the CNS.

Chemokine contributions to cancer metastasis

Long-term collaborative studies with Dr. Alessandro Fatatis (College of Medicine) have focused on the role of the chemokine receptor CX3CR1 in skeletal metastasis. Our work discovered that a novel CX3CR1 antagonist impairs breast cancer metastatic seeding to the skeleton by prolonging the cancer cells time in circulation and exposure to chemotherapy. Our more recent work uncovered that CX3CR1 expressing cancer cells are a rare subset with high expression of stemness genes, allowing them to resist chemotherapy and start new metastases. Therapeutic targeting of CX3CR1-expressing cancer cells could provide an effective approach to limit cancer progression and the metastatic cascade, a major cause of patient mortality.

Grant Funding

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Selected Publications

Van Duyne R, Irollo E, Lin A, Johnson JA, Guillem AM, O'Brien EV, Merja L, Nash B, Jackson JG, Sarkar A, Klase ZA, Meucci O
Cells. 13(13):1127. doi: 10.3390/cells13131127. PMID: 38994979 (2024)

Irollo E, Nash B, Luchetta J, Brandimarti R, Meucci O
J Neuroimmune Pharmacol. 18(3):495-508. doi: 10.1007/s11481-023-10082-x. PMID: 37661197 (2023)

Brandimarti R, Irollo E, Meucci O
Mol Neurobiol. 60(4):1811-1825. doi: 10.1007/s12035-022-03153-2. PMID: 36576708 (2022)

DiNatale A, Kaur R, Qian C, Zhang J, Marchioli M, Ipe D, Castelli M, McNair CM, Kumar G, Meucci O, Fatatis A
Oncogene. 41(9):1337-1351. doi: 10.1038/s41388-021-02174-w. PMID: 34999735 (2022)

Nickoloff-Bybel EA, Festa L, Meucci O, Gaskill PJ
Retrovirology. 18(1):24. doi: 10.1186/s12977-021-00569-x. PMID: 34429135 (2021)

Irollo E, Luchetta J, Ho C, Nash B, Meucci O
Cell Mol Life Sci. 78(9):4283-4303. doi: 10.1007/s00018-021-03785-y. PMID: 33585975 (2021)

Sulzer D, Antonini A, Leta V, Nordvig A, Smeyne RJ, Goldman JE, Al-Dalahmah O, Zecca L, Sette A, Bubacco L, Meucci O, Moro E, Harms AS, Xu Y, Fahn S, Ray Chaudhuri K
NPJ Parkinsons Dis. 6:18. doi: 10.1038/s41531-020-00123-0. PMID: 32885037 (2020)

Festa LK, Irollo E, Platt BJ, Tian Y, Floresco S, Meucci O
Elife. e49717. doi: 10.7554/eLife.49717. PMID: 31971513 (2020)

Nash B, Festa L, Lin C, Meucci O
Brain Res. 1723:146409. doi: 10.1016/j.brainres.2019.146409. PMID: 31465771 (2019)

Nash B, Tarn K, Irollo E, Luchetta J, Festa L, Halcrow P, Datta G, Geiger JD, Meucci O
eNeuro. ENEURO.0237-19.2019. doi: 10.1523/ENEURO.0237-19.2019. PMID: 31300544 (2019)

Renato Brandimarti, Gordon S. Hill, Jonathan D. Geiger & Olimpia Meucci
Scientific Reports, 7, Article number: 15103, doi:10.1038/s41598-017-15128-8 (2017)

Pitcher J., Abt A., Myers J., Han R., Snyder M., Graziano A., Festa L., Kutzler M., Garcia F., Gao WJ, Fisher-Smith T., Rappaport J. and Meucci O.
Journal of Clinical Investigation Jan 9. pii: 70090. doi: 10.1172/JCI70090. [Epub ahead of print]; PMID: 24401274 (2014)

Pitcher J., Wurth R., Shimizu S, and Meucci O.
Methods in Molecular Biology vol 1013; pp 31-48; DOI10.1007/978-1-62703-426-5_3 (2013)

Festa L. and Meucci O.
Current HIV Research, 10(5):453-62 PMID: 22591369 (2012)

Shimizu S, Brown M, Sengupta R, Penfold ME, and Meucci O
PLoS One, 6(5):e20680. Epub 2011 May 31 (2011)

Abt AC and Meucci O
Journal of NeuroImmune Pharmacology, Apr 5. [Epub ahead of print] (2011)

Nicolai J., Burbassi S., Rubin J., and Meucci O.
Cell Death and Disease (Nature Publishing Group) 1, e33; doi:10.1038/cddis.2010.10 (2010)

Sengupta R., Burbassi S., Shimizu S., Cappello S., Vallee R., Rubin J., and Meucci O.
The Journal of Neuroscience 29:2534-44 (2009)

Khan M.Z., Brandimarti R., Shimizu S., Nicolai J., Crowe E., and Meucci O
Cell Death & Differentiation (Nature Publishing Group) 15:1663-1672 (2008)