Title: Associate Professor
Education: Ph.D., Microbiology and Immunology (1998-2002): University of Kentucky. Post-doctoral training: Virology (2002-2003): University of Kentucky. Research Scientist II: Neuroscience (2003-2007): University of Kentucky. Assistant Professor: Pharmacology (2007-2014): Virginia Commonwealth University
Department(s): Immunology, Center for Personalized Nanomedicine
In the brain, long-lived cells such as meningeal macrophages, microglia, and astrocytes are the major cell types infected with HIV and potentially serve as reservoirs and sources of chronic infection. Further complicating the issue of the brain as an HIV reservoir are co-morbidities such as substance abuse that may alter the reservoir. We and others have shown the interactive effects of HIV and the opiate morphine in brain cells such as microglia and astrocytes to facilitate neuro-inflammation and other stressors; however, the mechanisms at play are still widely unknown. Furthermore, existing combined anti-retroviral therapeutic approaches have been limited in their ability to cross the blood-brain barrier effectively and recognize and selectively eliminate persistent reservoirs. We have discovered that activation of the host autophagic protein, Beclin1, by HIV-1 infection represents an essential mechanism in controlling viral replication and viral and morphine-induced inflammatory responses in microglial cells. Recently, we demonstrated that (i) the use of siRNA targeting the autophagy regulator Beclin1 (siBeclin1) can achieve inhibition of HIV replication and viral ± morphine-induced inflammation in infected microglial cells, and (ii) the use of intranasal delivery of an siBeclin1-linear polyethylenimine-nanoplex can be safely and effectively delivered to the brain. The long term goal is to develop adjunctive therapy along with cART that can attenuate HIV-replication and HIV and opioid-induced inflammation in brain reservoirs.
Additional research interests in my lab include:
- Determining whether dimerization of different μ-opioid receptor (MOR) splice variants with the co-receptor, CCR5, can regulate HIV cellular binding and entry in brain cells.
- Investigating the role of autophagy in the pathogenesis of Zika virus (ZIKV)-associated microcephaly using autophagy-deficient mouse model.
Selected peer-reviewed publications:
- El-Hage N, Gurwell JA, Singh IN, Knapp PE, Nath A and Hauser KF. Synergistic increases in intracellular Ca2+, and the release of MCP-1, RANTES, and IL-6 by astrocytes treated with opiates and HIV-1 Tat. Glia 2005. PMID: 15630704
- El-Hage, N, Bruce-Keller AJ, Yakovleva T, Bazov I, Bakalkin G, Knapp PE and Hauser KF. Morphine exacerbates HIV-1 Tat-induced cytokine production in astrocytes through convergent effects on [Ca2+]I, NF-κB trafficking and transcription, PLoS One 2008. PMID: 19116667
- Zou S, Fitting S, Yun KH, Welch S, El-Hage N, Hauser KF and Knapp PE. Morphine potentiates neurodegenerative effects of HIV-1 Tat through action at μ opioid receptor expressing glia. Brain 2011. PMID: 22102648
- El-Hage N, Rodriguez M, Dever SM, Masvekar RR, Gewirtz DA and Shacka JJ. HIV-1 and morphine regulation of autophagy in microglia: Limited interactions in the context of HIV-1 infection and opioid abuse. J Virol. 2015. PMID: 25355898
- Rodriguez M, Kaushik A, Lapierre J, Dever SM, El-Hage N and Nair M. Electro-Magnetic Nano-Particle Bound Beclin1 siRNA Crosses the Blood-Brain Barrier to Attenuate the Inflammatory Effects of HIV-1 Infection in Vitro. Journal NeuroImmune Pharmacol. 2016; PMID: 27287620
- Rodriguez M, Lapierre J, Ojha CR, Kaushik A, Batrakova E, Kashanchi F, Dever SM, Nair M, El-Hage N. Intranasal drug delivery of small interfering RNA targeting Beclin1 encapsulated with polyethylenimine (PEI) in mouse brain to achieve HIV attenuation. Sci Rep. PMID: 285003269