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Targeting Neurocognitive Impairment in HIV Infection: HAND in HAND with Chemokines
Start Date: 2/6/2019Start Time: 4:00 PM
End Date: 2/6/2019End Time: 5:30 PM
Event Description
BIOMED Seminar

Targeting Neurocognitive Impairment in HIV Infection: HAND in HAND with Chemokines

Olimpia Meucci, MD, PhD
Professor and Chair, Department of Pharmacology and Physiology
Professor, Department of Microbiology and Immunology
Director, Center of Neuroimmunology and CNS Therapeutics
Institute of Molecular Medicine and Infectious Diseases
Drexel University College of Medicine

HIV-associated neurocognitive disorder (HAND) is characterized by deficits in cognitive, motor, and sensory processing that may range from minor impairment to dementia in the most severe cases. Although modern antiretroviral therapy (ART) effectively controls HIV replication, reduced HAND severity, and significantly improved patient survival and quality of life, there are still no effective treatments for HAND. Approximately 50% of ART treated patients still present with HAND spectrum pathology. Development of less severe HAND is also a risk factor for overall HIV disease progression. Additionally, HAND is often exacerbated by other variables including drug abuse, aging, inflammation, and inherent toxicity of ART.

Another limiting factor is our insufficient understanding of the mechanistic basis underlying the neuronal dysfunction that ultimately leads to the different forms of neurological impairment. While widespread cell loss and macroscopic alterations are rare features of neuropathology in the ART era, region specific and subtle changes of the synaptodendritic arbor, such as alterations in dendritic spine shape and density, are thought to be an important component of disease. At minimum, these changes are a manifestation of deficiencies in neuronal connectivity leading to cognitive deficit. This underscores the need for sensitive technologies that assess both structural and functional neuronal deficit, and for studying these alterations in a region specific manner – as also suggested by clinical imaging studies.

Our findings suggest that cognitive impairment in HAND is correlated to decreased dendritic spine density in prefrontal cortex (PFC) neurons, which is influenced by several factors such as HIV proteins, chronic inflammation, and opioid use. Importantly, our recent work on the CXCL12/CXCR4 chemokine axis (a major orchestrator of CNS homeostasis and repair) revealed that this process might be reversible. On the other hand, studies in multiple species - including humans - demonstrate that opioids compromise this pathway, representing a potential mechanism of accelerated HAND. These and other important aspects concerning the interplay of host, viral, and environmental factors in HIV neuropathology will be discussed in the seminar.

Olimpia Meucci, MD, PhD, is Professor and Chair of the department of Pharmacology and Physiology at Drexel University College of Medicine (DUCOM) ; she is also Professor of Microbiology and Immunology at DUCOM and head of the Center of Neuroimmunology and CNS Therapeutics of Drexel’s Institute of Molecular Medicine & Infectious Diseases. Dr. Meucci has been involved with the fields of neuroimmunology, molecular pharmacology, and signaling since the early stages of her scientific and medical career with a primary interest in neuroHIV. Her work as AIDS research fellow and junior faculty at the University of Chicago (1994-2000) significantly contributed to the initial characterization of the neuronal/glial alterations caused by HIV infection of the CNS and the role of selected chemokine-receptor pairs in neuronal survival and function. These initial seminal studies revealed unexpected functions of chemokines on brain cells and pioneered new research on the neuroprotective and homeostatic action of some of these proteins. This work formed the basis of her subsequent research at Drexel University College of Medicine (2000-present) - where she developed a productive research program funded by NIH (NIDA, NIMH, NCI), and other organizations.

A secondary area of research in the lab, which is also related to chemokine pathophysiology and drug discovery, concerns the role of chemokines in inflammatory breast cancer and brain metastasis. The long-term goal of these projects is the development of novel therapeutic strategies for the treatment of HAND and other cognitive disorders. With this long-term goal in mind, Dr. Meucci has been participating in a number of intramural and extramural initiatives that promote multidisciplinary collaborations and translational research. For instance, in addition to her role within the IMMID, she served as Deputy Director of Drexel’s Clinical and Translational Research Institute (2013-2016), she was the mastermind of the MOU for students and faculty exchange between Drexel University and the University of Bologna (signed in 2018).

Dr. Meucci has been a member of NIH review panels since the early 2000s and is affiliated with a number of scientific societies, such as SFN, ISNV and SNIP, and has served these organizations in different leadership capacities over the years. She is a member of Editorial Boards; most recently, she was invited to join the Nature Publishing Group as an editor of Scientific Reports, and is currently editing a new book on “HIV and Cognitive Decline” for Brain Research. In recognition of her contribution to the field, Dr. Meucci was recently selected to receive the prestigious MERIT award (R37) from the National Institute on Drug Abuse, which will continue to support her research.
Contact Information:
Name: Ken Barbee
Phone: 215-895-1335
Olimpia Meucci
Papadakis Integrated Sciences Building (PISB), Room 120, located on the northeast corner of 33rd and Chestnut Streets.
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