Raj Dave, PhD

daveInstructor - Department of Neurological Sciences

Professional Summary
Research Interests
Biographical Information
Chronic HIV in Aging and NeuroAIDS (CHAIN) Center
Nebraska Center for Substance Abuse Research (NCSAR)

Academic Office:
Laboratory of Howard Fox and Shilpa Buch
Durham Research Center II, Room 3070
985800 Nebraska Medical Center
Omaha, NE  68198-5930
Phone: (402) 836-9717
Email

Education:

Professional Summary:
My research has been focused on HIV infection. Areas of expertise include: molecular virology, neurobiology and immunology. Areas of research focus include: HIV infection of the Central Nervous System, Opioid abuse, neuro-inflammation, oxidative stress, miRNAs, comorbidities and viral reservoirs.

Keywords: HIV, neuroHIV, miRNA, opiates, exosomes, drugs of abuse

Research Interests:
My research interests include elucidating role of miRNAs in genomic adaptation of HIV CNS disease in opiate-abusers and related co-infections.

Opiate-abusers are at a high-risk for Human Immunodeficiency Virus (HIV) infection.
In USA 30% of HIV-infected individuals are opiate-abusers and new HIV infections continue to increase. These individuals experience severe psychological stress, neurological-dysfunction, depression & hepatitis-C virus infection. More importantly, the resultant high-risk sexual behavior, poor adherence to antiretroviral regimens and onset of co-morbid conditions such as hepatitis-C virus infection collectively accelerate disease progression. As HIV replication in the central nervous system (CNS) cannot be inhibited efficiently despite advances in antiretroviral therapy efficacy, latent viral reservoir is established in the CNS. Since the antiretrovirals poorly access the CNS, reactivation of the latent virus manifests in a broad range of HIV-associated neurocognitive disorders that could include HIV-associated dementia (HAD), HIV encephalitis (HIVE), or mild cognitive motor dysfunction (MCMD). Viral proteins and pro-inflammatory cytokines and chemokines secreted by HIV-infected microglia and perivascular macrophages induce inflammation and oxidative damage. As a result, HIV-infected opiate-abusers are susceptible to accelerated disease progression and neurological dysfunction.

My current research interest is focused on investigating the role of microRNAs (miRNAs) and inflammation, in HIV neuropathogenesis in opiate-abusers. As evidenced from our studies in h-mdms and fetal cells derived from the CNS, there is a strong basis for implicating miRNAs and inflammation in the neuroAIDS paradigm. These studies indicate that pathologic (HIV) and biochemical (opiates) insults to the CNS induce inflammation and alter miRNA expression. In this paradigm we observed differential expression of 26 miRNAs (p<0.01) from h-­mdms exposed to morphine. Importantly, miRNAs (15b/21) that could intersect neurogenesis and cell cycle regulation were identified to be responsive to morphine. Interestingly, expression of this miRNA pair (15b/21) was inversely correlated in morphine-exposed h-mdms, with miR15b exhibiting the strongest expression. Of note, a direct correlation was observed between miR15b (strongest induction) and suppression of its target gene expression fibroblast growth factor-2 (FGF-2). In parallel we have observed an induction of potent inflammatory response from morphine-­exposed h-mdms resulting in secretion of interleukin-6 (IL-6), monocyte chemoattractant protein 2 (MCP-2) and tumor necrosis factor α (TNF-α). These results provide insights into how macrophage/microglia may affect disease progression in HIV-­infected opiate-abusers. However, the role of miRNAs and inflammation in these disease processes is not clearly understood and has to be further elucidated.

Positions and Employment:

2019 - present

Instructor, Department of Neurological Sciences,

University of Nebraska Medical Center, Omaha, NE (Mentor: Dr. Howard S. Fox)

2019 - 2020

Instructor, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE (Mentor: Dr. Howard S. Fox)

2017 - 2019    

Instructor, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE (Mentor: Dr. Sid Byrareddy)

2014 - 2016 

Instructor, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA (Mentor: Dr. Brian Wigdahl)

2008 - 2014

Associate Scientist, Center for Neurovirology, Department of Neuroscience, Temple University, Philadelphia, PA (Mentor: Dr. Kamel Khalili)

2008

Scientific Writer, Merck Research Laboratories, North Wales, PA

2007 - 2008

Research Instructor, Department of Medicine, Thomas Jefferson University, Philadelphia, PA (Mentor: Dr. Kathleen Squires)

2002 - 2007

Postdoctoral Fellow, Department of Medicine, Thomas Jefferson University, Philadelphia, PA (Mentor Dr. Roger J. Pomerantz)

2000 - 2007

Postdoctoral Fellow, Department of Pathology, Columbia University, New York NY (Mentor: Dr. David J. Volsky)

1999 - 2000

Postdoctoral Fellow, Department of Molecular Virology, Medical Genetics and Molecular Medicine, Ohio State University, Columbus, OH (Mentor: Dr. Kunal Saha)

1998 - 1999

Postdoctoral Fellow, Department of Pathology, Columbia University, New York NY (Mentor: Dr. David J. Volsky)

Select Publications: 

*Corresponding author

Dave RS, Ali H, Sil S, Knight LA, Pandey K, Madduri LSV, Qiu F, Ranga U, Buch S, Byrareddy SN. NF-κB Duplications in the Promoter-Variant HIV-1C LTR Impact Inflammation Without Altering Viral Replication in the Context of Simian Human Immunodeficiency Viruses and Opioid-Exposure. Front Immunol. 2020;11:95. doi: 10.3389/fimmu.2020.00095. eCollection 2020. PubMed PMID: 32076422; PubMed Central PMCID: PMC7006833.

Jaffe RJ, Dave RS, Byrareddy SN. Meningeal lymphatics in aging and Alzheimer's disease. Ann Transl Med. 2019 Mar;7(Suppl 1):S2. doi: 10.21037/atm.2019.01.06. PubMed PMID: 31032283; PubMed Central PMCID: PMC6462592.

Dave RS, Jain P, Byrareddy SN. Follicular Dendritic Cells of Lymph Nodes as Human Immunodeficiency Virus/Simian Immunodeficiency Virus Reservoirs and Insights on Cervical Lymph Node. Front Immunol. 2018;9:805. doi: 10.3389/fimmu.2018.00805. eCollection 2018. Review. PubMed PMID: 29725333; PubMed Central PMCID: PMC5916958.

Dave RS, Jain P, Byrareddy SN. Functional Meningeal Lymphatics and Cerebrospinal Fluid Outflow. J Neuroimmune Pharmacol. 2018 Jun;13(2):123-125. doi: 10.1007/s11481-018-9778-5. Epub 2018 Feb 20. PubMed PMID: 29464588; PubMed Central PMCID: PMC5930060.

Dave RS, Sharma RK, Muir RR, Haddad E, Gumber S, Villinger F, Nehra AP, Khan ZK, Wigdahl B, Ansari AA, Byrareddy SN, Jain P. FDC:TFH Interactions within Cervical Lymph Nodes of SIV-Infected Rhesus Macaques. J Neuroimmune Pharmacol. 2018 Jun;13(2):204-218. doi: 10.1007/s11481-017-9775-0. Epub 2017 Dec 29. PubMed PMID: 29288344; PubMed Central PMCID: PMC5757373.

Dave RS*Morphine affects HIV-induced inflammatory response without influencing viral replication in human monocyte-derived macrophages. FEMS Immunol Med Microbiol. 2012 Mar;64(2):228-36. doi: 10.1111/j.1574-695X.2011.00894.x. PubMed PMID: 22066570; PubMed Central PMCID: PMC3336009.

Regan PM, Dave RS, Datta PK, Khalili K. Epigenetics of µ-opioid receptors: intersection with HIV-1 infection of the central nervous system. J Cell Physiol. 2012 Jul;227(7):2832-41. doi: 10.1002/jcp.24004. Review. PubMed PMID: 22034138; PubMed Central PMCID: PMC3971722.

Dave RS*, Khalili K. Morphine treatment of human monocyte-derived macrophages induces differential miRNA and protein expression: impact on inflammation and oxidative stress in the central nervous system. J Cell Biochem. 2010 Jul 1;110(4):834-45. doi: 10.1002/jcb.22592. PubMed PMID: 20564181; PubMed Central PMCID: PMC2923828.

Dave RS*. RNAi and tumor angiogenesis: bridging the gap towards anti-cancer therapy?. Leuk Res. 2007 Apr;31(4):421-2. doi: 10.1016/j.leukres.2006.10.024. Epub 2006 Dec 8. PubMed PMID: 17157908.

Fang J, Acheampong E, Dave R, Wang F, Mukhtar M, Pomerantz RJ. The RNA helicase DDX1 is involved in restricted HIV-1 Rev function in human astrocytes. Virology. 2005 Jun 5;336(2):299-307. https://doi.org/10.1016/j.virol.2005.03.017. PubMed PMID: 15892970.

Dave RS*, Pomerantz RJ. HIV-1 Neuropathogenesis: Persistent Infection, Persistent Questions. Science and Medicine. 2005; 10(2):112.

Dave RS, Pomerantz RJ. Antiviral effects of human immunodeficiency virus type 1-specific small interfering RNAs against targets conserved in select neurotropic viral strains. J Virol.2004 Dec;78(24):13687-96. doi: 10.1128/JVI.78.24.13687-13696.2004. PubMed PMID: 15564478; PubMed Central PMCID: PMC533941.

Dave RS, Pomerantz RJ. RNA interference: on the road to an alternate therapeutic strategy! Rev Med Virol. 2003 Nov-Dec;13(6):373-85. https://doi.org/10.1002/rmv.407 Review. PubMed PMID: 14625885.

Saha K, Zhang J, Gupta A, Dave R, Yimen M, Zerhouni B. Isolation of primary HIV-1 that target CD8+ T lymphocytes using CD8 as a receptor. Nat Med. 2001 Jan;7(1):65-72. doi: 10.1038/83365. PubMed PMID: 11135618.

Dave RS, Mitra RK. A low temperature induced apoplastic protein isolated from Arachis hypogaea. Phytochemistry. 1998 Dec;49(8):2207-13. doi: 10.1016/s0031-9422(98)00372-0. PubMed PMID: 9887521.

Additional publications in PubMed