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Olimpia Meucci

Olimpia Meucci, MD, PhD

Professor & Chair


Department: Pharmacology & Physiology

Education

  • MD, PhD - University of Naples, Italy (1994)

Awards & Honors

  • Daniel V. Schidlow, MD, Transformational Leadership Award, Drexel University College of Medicine (2023)
  • Elected to the National Academy of Inventors (2020)
  • Elias Abrutyn Mentoring Award, Drexel University College of Medicine (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, Drexel University College of Medicine (2011)
  • Excellence in Research Award, Drexel University (2002/03, 2003/04)

Olimpia Meucci, MD, PhD is a tenured professor and chair of the Department of Pharmacology & Physiology at Drexel University College of Medicine. Dr. Meucci actively contributes to the scientific and academic missions of the College's graduate and medical schools. Her interdisciplinary research projects support students from different programs training in her laboratory, and she leads a variety of interdisciplinary and translational research efforts. A prime example is the TRaCES initiative (Translational Research and Core Expert Support), which helps scientists and clinicians collaborate on translational research projects.

Dr. Meucci holds a secondary appointment in the Department of Microbiology & Immunology, in which she served as co-director of the Temple/Drexel/UPenn training grant “Interdisciplinary and Translational Research Training in NeuroAIDS” (NIH-MH079785). She also directs the Center of Neuroimmunology and CNS Therapeutics, which is part of the Institute for Molecular Medicine and Infectious Diseases (IMMID).

Research Overview

Research Interests

HIV-associated neurocognitive disorders and drug abuse, chemokine-based therapeutics, neuroprotective pathways in neuroinflammation

Research

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 – 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’s 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’s 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-β 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

Active grants

NIH-NIDA 2 R01 DA015014; Transformed to R37-DA015014 MERIT award, 2018-2028
Principal Investigator: Meucci
Project Title: Role of chemokine receptors in neuronal survival

NIH-NIDA 2 R01 DA032444
Principal Investigator: Meucci
Project Title: Effects of opiates on neurons and their impact on HIV neuropathology

NIH-NIDA 1 R21 DA056309
Principal Investigators: Meucci, Klase, Jackson
Project Title: Adult human brain tissue cultures to study neuroHIV

NIH-NIMH 5 T32 MH079785
Program Director: T. Burdo, PI/Co-PI-subcontract: Wigdahl/Meucci
Project Title: Interdisciplinary and Translational Research Training in NeuroHIV

NIH-NIDA 1 R61 DA058501
Principal Investigator: Gaskill, Co-Investigator: Meucci
Project Title: Defining molecular mechanisms by which stimulant evoked dopamine drives inflammation and neuronal dysfunction in neuroHIV

NIH-NIMH 1 K01 MH132466
Principal Investigator: Matt, Co-mentor: Meucci
Project Title: The role of antidepressants in central and peripheral myeloid HIV persistence and inflammation

NIH-NIDA 1 F32 DA060768
Principal Investigator: Namba, Sponsor: Barker, Co-Sponsor: Meucci
Project Title: Corticolimbic circuit and neuroimmune mechanisms of comorbid HIV and cocaine use

NIH-NIAID 1 F30 AI179472
Principal Investigator: Channer, Sponsor: Gaskill, Co-Sponsor: Meucci
Project Title: Dopaminergic immunomodulation drives macrophage inflammation during HIV infection

Completed grants

NIH-NCI 1 R01 CA202929
Principal Investigators: Fatatis, Meucci
Project Title: Role of CX3CR1 in breast cancer metastasis

NIH-NIDA 1 R21 DA040519
Principal Investigator: Meucci
Project Title: Effects of HIV neurotoxins on lipid rafts-associated proteins

Coulter Foundation
Principal Investigators: Fatatis, Meucci
Project Title: Small molecule compounds for the therapy of metastatic cancer

Breast Cancer Alliance
Principal Investigator: Fatatis, co-Investigators: Meucci/Salvino
Project Title: New Small molecule compounds for the therapy of metastatic cancer

NIH-NIMH 1 R21 MH097623
Principal Investigators: Waterhouse, Meucci, Torres, Gao, Shumsky
Project Title: HIV gp120 and Prefrontal Cortical Function

Restless Leg Syndrome Foundation
Principal Investigator: Padma Ponnuru, Mentor: Meucci
Project Title: A role for MEIS 1 in iron brain deficiency in RLS

US Army Public Health Command CTC/CHPPM (RFQ# 09-0344)
Principal Investigator: Meucci
Project Title: Mechanism of action of RDX neuronal toxicity

NIH-NIDA 1 R01 DA19808
Principal Investigator: Meucci
Project Title: Cellular and Molecular Mechanisms of HIV Neuropathology

NIH-NIGMS 1 R01 GM067892
Principal Investigator: Fatatis, Co-Investigator: Meucci
Project Title: Role of intracellular sphingolipids in Ca signaling

NIH-NIDA 1 F31 DA020234
Principal Investigator: Jeegar Patel, Mentor: Meucci
Project Title: Interactions of opioid and chemokine receptors systems in neurons

Drexel University Synergy Grant
Principal Investigators: Yuan (Dept. of Physics), Meucci
Project Title: A system approach to CXCR4 receptor regulation of survival pathways in neurons and glia

W.W. Smith Charitable Trust A0302
Principal Investigator: Meucci
Project Title: Cell cycle proteins and HIV neuropathogenesis

American Foundation AIDS Research 2816-30-RG
Principal Investigator: Meucci
Project Title: Role of cell cycle proteins in HIV-Neurodegeneration

Publications

See all Olimpia Meucci's publications in PubMed.

Selected Publications

“Adult Human Brain Tissue Cultures to Study NeuroHIV”
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)

“The Endolysosomal Transporter DMT1 is Required for Morphine Regulation of Neuronal Ferritin Heavy Chain”
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)

“The US9-Derived Protein gPTB9TM Modulates APP Processing Without Targeting Secretase Activities”
Brandimarti R, Irollo E, Meucci O
Mol Neurobiol. 60(4):1811-1825. doi: 10.1007/s12035-022-03153-2. PMID: 36576708 (2022)

“Subsets of cancer cells expressing CX3CR1 are endowed with metastasis-initiating properties and resistance to chemotherapy”
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)

“Co-receptor signaling in the pathogenesis of neuroHIV”
Nickoloff-Bybel EA, Festa L, Meucci O, Gaskill PJ
Retrovirology. 18(1):24. doi: 10.1186/s12977-021-00569-x. PMID: 34429135 (2021)

“Mechanisms of neuronal dysfunction in HIV-associated neurocognitive disorders”
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)

“COVID-19 and possible links with Parkinson's disease and parkinsonism: from bench to bedside”
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)

“CXCL12-induced rescue of cortical dendritic spines and cognitive flexibility”
Festa LK, Irollo E, Platt BJ, Tian Y, Floresco S, Meucci O
Elife. e49717. doi: 10.7554/eLife.49717. PMID: 31971513 (2020)

“Opioid and chemokine regulation of cortical synaptodendritic damage in HIV-associated neurocognitive disorders”
Nash B, Festa L, Lin C, Meucci O
Brain Res. 1723:146409. doi: 10.1016/j.brainres.2019.146409. PMID: 31465771 (2019)

“Morphine-Induced Modulation of Endolysosomal Iron Mediates Upregulation of Ferritin Heavy Chain in Cortical Neurons”
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)

The lipid raft-dwelling protein US9 can be manipulated to target APP compartmentalization, APP processing, and neurodegenerative disease pathogenesis
Renato Brandimarti, Gordon S. Hill, Jonathan D. Geiger & Olimpia Meucci
Scientific Reports, 7, Article number: 15103, doi:10.1038/s41598-017-15128-8 (2017)

Neuronal ferritin heavy chain and drug abuse affect HIV-associated cognitive dysfunction
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)

Multispectral imaging and automated laser capture microdissection of human cortical neurons: a quantitative study of CXCR4 expression
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)

Effects of opiates and HIV proteins on neurons: the role of ferritin heavy chain and a potential for synergism
Festa L. and Meucci O.
Current HIV Research, 10(5):453-62 PMID: 22591369 (2012)

CXCR7 protein expression in human adult brain and differentiated neurons
Shimizu S, Brown M, Sengupta R, Penfold ME, and Meucci O
PLoS One, 6(5):e20680. Epub 2011 May 31 (2011)

Regulation of Neuronal Ferritin Heavy Chain, A New Player in Opiate-Induced Chemokine Dysfunction
Abt AC and Meucci O
Journal of NeuroImmune Pharmacology, Apr 5. [Epub ahead of print] (2011)

CXCL12 inhibits expression of the NMDA receptor's NR2B subunit through a Histone deacetylase-dependent pathway contributing to neuronal survival
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)

Morphine increases brain levels of ferritin heavy chain leading to inhibition of CXCR4-mediated survival signaling in neurons
Sengupta R., Burbassi S., Shimizu S., Cappello S., Vallee R., Rubin J., and Meucci O.
The Journal of Neuroscience 29:2534-44 (2009)

The chemokine CXCL12 promotes survival of postmitotic neurons by regulating Rb protein
Khan M.Z., Brandimarti R., Shimizu S., Nicolai J., Crowe E., and Meucci O
Cell Death & Differentiation (Nature Publishing Group) 15:1663-1672 (2008)