Dr. Zhu’s research aims toward finding solutions to a newly recognized challenge in treatment for HIV-associated neurocognitive disorders (HANDs). For a long time, the idea of the HIV virus crossing the blood-brain barrier was not even considered, but it’s now clear that HIV-1 viral proteins are released in the brain, where they disrupt normal brain functions.
About one-half of HIV-1-positive individuals suffer from HAND, which dramatically affects memory, learning, decision-making, planning, and overall quality of life. Drugs of abuse, such as cocaine, have been shown to exacerbate the severity of HAND. HAND is associated with HIV-1 viral proteins, which are present in the brain of HIV-1-infected patients. HIV-1 transactivator of transcription (Tat) protein, a HIV regulatory protein, is thought to inhibit neuronal communication by acting directly on the human dopamine transporter (hDAT), a membrane protein in the brain responsible for pumping the dopamine back into the cytosol and terminating dopamine signaling during neurotransmission.
In collaboration with several researchers at other Universities, Dr. Zhu has established a National Institutes of Health (NIH)-funded research project to develop advanced approaches that integrate computational modeling with molecular pharmacology to investigate how cocaine and Tat work to create binders that derail neuronal communication in the brain. Dr. Zhu’s research has recently been highlighted in the field of HIV research by Nature Chemical Biology. The ultimate goal is to develop neuroprotective drugs, which can help HIV patients recover their neurological function.
Dr. Zhu’s laboratory also is exploring new theories about why some people may be more predisposed to addiction than others, and whether preemptive treatments could stop people from becoming addicted in the first place. Tobacco use is the number one preventable cause of death in the United States. This project is to study how environmental factors, through modulation of small RNAs and intracellular signaling, reduce nicotine’s rewarding effects. This research project will provide insights into impact of a unique microRNA regulation in drug rewarding, and has a high impact in the field of drug abuse research.
Postdoctoral Fellow-Neuropharmacology, (2006)
University of Kentucky
Doctor of Philosophy, Biochemistry 1998
Fukui Medical University
Doctor of Medicine, 1982
- HIV-1 Tat protein-mediated regulation
of human dopamine transporter.
- MicroRNA regulation of signaling pathways
and vulnerability to nicotine dependence.
- Drug addiction
1. Zhu J, Yuan Y, Midde NM, Gomez AM, Sun WL, Quizon PM, Zhan CG. HIV-1 transgenic rats display an increase in [3H]dopamine uptake in the prefrontal cortex and striatum. Journal of NeuroVirology. 2015 Oct 26. [Epub ahead of print] PMID:
26501780 (as a corresponding author).
2. Gomez AM, Altomare D, Sun WL, Midde NM, Ji H, Shtutman M, Turner JR, Creek KE, Zhu J. Prefrontal microRNA-221 mediates environmental enrichment-induced increase of locomotor sensitivity to nicotine. The International Journal of Neuropsychopharmacology. 2015. PMID: 26232787 (as a corresponding author)
3. Sun WL, Quizon PM, McGinty JF, Zhu J. Molecular mechanism: ERK signaling, drug addiction and behavioral effects. (Invited review) Progress in Molecular Biology and Translational Science 2015. (in Press) (as a corresponding author)
4. Zhu J, Midde NM, Gomez AM, Sun WL, Harrod SB. Intra-ventral tegmental area HIV-1 Tat1-86 attenuates nicotine-mediated locomotor sensitization and alters mesocorticolimbic ERK and CREB signaling in rats. Frontier in Microbiology 2015. PMCID: PMC4473058 (as a corresponding author)
5. Yuan Y, Huang X, Midde NM, Quizon PM, Sun WL, Zhu J, Zhan CG. Molecular mechanism of HIV-1 Tat interacting with human dopamine transporter. ACS Chemical Neuroscience 2015. PMCID: PMC4400243
6. Midde NM, Yuan Y, Quizon PM, Sun WL, Huang X, Zhan CG, Zhu J. Mutations at Tyrosine 88, Lysine 92 and Tyrosine 470 of Human Dopamine Transporter Result in an Attenuation of HIV-1 Tat-Induced Inhibition of Dopamine Transport. J Neuroimmune Pharmacol 2015. PMID: 25604666 (as a corresponding author)
7. Gomez AM, Sun WL, Midde NM, Harrod SB, Zhu J. Effects of environmental enrichment on ERK1/2 phosphorylation in the rat prefrontal cortex following nicotine-induced sensitization or nicotine self-administration. European Journal of Neuroscience 2015. 41(1):109-19 PMCID: PMC4285565 (as a corresponding author)
8. Midde NM, Huang X, Gomez AM, Booze RM, Zhan CG, Zhu J. Mutation of Tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions. J Neuroimmune Pharmacol 8:975-987, 2013. PMCID: PMC3740080 (as a corresponding author)
9. Gomez AM, Midde NM, Mactutus CF, Booze RM, Zhu J. Environmental Enrichment Alters Nicotine-Mediated Locomotor Sensitization and Phosphorylation of DARPP-32 and CREB in Rat Prefrontal Cortex. PLos One 7(8):e44149, 2012. PMCID: PMC3432100 (as a corresponding author)
10. Midde NM, Gomez AM, Zhu J. HIV-1 Tat Protein Decreases Dopamine Transporter Cell Surface Expression and Vesicular Monoamine Transporter-2 Function in Rat Striatal Synaptosomes. J Neuroimmune Pharmacol 7(3):629-639, 2012. PMCID: PMC3688268 (as a corresponding author)
11. Zhu J, Ananthan S, Mactutus CF and Booze RM. Recombinant human immunodeficiency virus-1 transactivator of transcription (1-86) allosterically modulates dopamine transporter activity. Synapse 65:1251-1254. 2011 PMCID: PMC3676522 (as a corresponding author)
12. Midde NM, Gomez AM, Harrod SB and Zhu J. Genetically expressed HIV-1 viral proteins attenuate nicotine-induced behavioral sensitization and alter mesocorticolimbic ERK and CREB signaling in rats. Pharmacol Bio Behav 98:587-597. 2011 PMCID: PMC3091851 (as a corresponding author)
13. Zhu J, Mactutus CF, David R Wallace, Booze RM. HIV-1 Tat protein-induced rapid and reversible decrease in [3H]dopamine uptake: Dissociation of [3H]dopamine uptake and [3H]WIN 35,428 binding in rat striatal synaptosomes. J Pharmacol Exp Ther 329:1071-1083. 2009 PMCID: PMC2683782 (as a corresponding author)