Image of Meucci, Olimpia

Olimpia Meucci, MD, PhD

Professor

  • Department:Pharmacology & Physiology
  • Education:  MD, PhD, University of Naples, Italy (1994)
Research Overview

The overall goals in Dr. Meucci’s laboratory are to identify targets for novel therapeutic approaches against neurodegenerative/neuroinflammatory disorders and contribute to the development of neuroprotective drugs. 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 drug abuse, an active area of research in the laboratory is the interaction of opiates with the endogenous chemokine system – a crucial regulator of both immune and nervous system function.

Work from the Meucci lab has significantly contributed to the current knowledge of chemokine physiopathology in the central nervous system (CNS) and to the identification of cellular and molecular mechanisms of HIV neuropathogenesis, revealing promising therapeutic targets against HAND and other neurodegenerative disorders. These efforts have focused on the CXCL12/CXCR4 and the CX3CL1/CX3CR1 chemokine-receptor pairs, which are both constitutively expressed in the CNS and involved in essential neuronal and glia functions. The experimental approaches used in the lab include in vitro, ex vivo, and in vivo model systems (i.e., primary neuronal and glial cultures, brain slices, animal models, and human specimens) aimed to investigate mechanisms of disease at the cellular/molecular and system level. Additional collaborative projects relate to the role of chemokines in cancer.

This research has been funded by the NIH and other organizations since 2001, and the most significant accomplishments have been in the following main areas. Please visit the lab webpage for additional details.

  • Mechanisms of HIV-induced neuronal damage and identification of potential pharmacologic targets for HAND
    Innovative discoveries about the multiple effects of HIV proteins on different brain cells revealed the complexity of the mechanisms underlying HIV-neuropathology. These studies have drawn the attention of the scientific community to the necessity of a multifaceted approach for the treatment of HAND. This supports the need for adjuvant neuroprotective therapies targeting both neuronal and glial cells in antiretroviral-treated patients.
  • Chemokine receptors in the CNS
    Novel roles and regulatory factors: The lab has identified novel roles of chemokines in differentiated neurons, such as regulation of neuronal-glial communication, neurotransmission, and excitotoxicity. These findings elucidated some of the molecular players that lead to neuronal injury. By revealing the link of certain chemokine receptors to neuronal survival and function, these discoveries have been instrumental in predicting potential consequence of chemokine alteration or manipulation under normal and pathological conditions, and in the exploration of new therapeutic approaches to reduce neuroinflammation and neuronal damage in the adult brain.
  • Impact of the opiate-chemokine interaction in HAND
    Discoveries concerning the regulation of the CXCR4 chemokine receptors by opiates, including morphine, have revealed unexpected factors responsible for HIV neuropathology that may be particularly relevant to the HIV+ population of drug users. Importantly, these studies have unveiled a novel function of the iron storage protein ferritin heavy chain, which may have much larger implications both within and outside the CNS.
  • Chemokine-based methods for inhibiting cancer metastasis
    Long-term collaborative studies with Dr. Alessandro Fatatis (DUCOM)  have focused on the role of the chemokine receptor CX3CR1 in skeletal metastasis. Work with other collaborators (Dr. Benovic at Thomas Jefferson University and Dr. Rubin at Washington University in St. Louis) has examined alterations of CXCR4 signaling in cancer cells. These efforts have recently led to the generation of patented small molecule compounds (synthesized by Dr. Salvino, DUCOM) that show promise for the treatment of skeletal metastasis in breast and prostate cancer patients.

Read Dr. Meucci's Women in Medicine and Science Committee highlight.

Publications

Selected Publications (See all Olimpia Meucci's publications in PubMed.)

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)

Teaching

As a tenured professor in the Department of Pharmacology & Physiology at Drexel University College of Medicine, Dr. Meucci actively contributes to the educational mission of the College's graduate and medical schools. Due to the interdisciplinary nature of her work, students from different graduate programs usually train in her laboratory, and she also holds a secondary appointment in the Department of Microbiology & Immunology. In addition to her involvement in various institutional and extramural committees, Dr. Meucci is one of the co-directors of the Temple/Drexel/UPenn training grant “Interdisciplinary and Translational Research Training in NeuroAIDS” (NIH-MH079785), director of the Center of Neuroimmunology and CNS Therapeutics, which is part of the Institute of Molecular Medicine and Infectious Diseases (IMMID), and deputy director of the Clinical and Translational Research Institute (CTRI) of Drexel University.

Research Location

Department of Pharmacology & Physiology
245 North 15th Street
Mail Stop #488
Philadelphia, PA 19102
Phone: 215-762-2597
Fax: 215-762-2299

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