Zhi “Elena” Zhang, M.D., Ph.D.

Associate Professor of Neurobiology
Zhi “Elena” Zhang
College of Arts, Sciences, and Letters
Natural Sciences
[email protected]
313-583-6577

Teaching Areas:

Biological Sciences

Research Areas:

Neurobiology, Neuroscience

Biography and Education

  • Ph.D., Biology/Neuroscience, Wesleyan University, Middletown; research area: NMDA receptor-mediated neuroplasticity in learning and memory.
  • M.S., Molecular Neurobiology, Beijing Institute for Brain Disorders, Beijing, China; research area: gene therapy in Parkinson's disease
  • M.D., Clinical Medicine, Capital Medical University, Beijing, China

Teaching and Research

Research

My research goal is to discover the underlying mechanisms of neurological disorders and develop therapies for the treatment of these disorders. In both my previous and current research I have explored the cellular and molecular mechanisms of cortical function and plasticity under physiological and pathological conditions. In recent years, growing evidence shows a link between intrauterine/perinatal experiences and the development of neurological and psychiatric disorders later in life. Studies show that neuroinflammation and neurotoxicity induced by infection and trauma can impair early brain development, which can increase the risk for age-associated neurodegenerative disease and modify disease progression. Findings from my research indicate that prenatal infections and perinatal brain trauma can induce prolonged neuroinflammation and glutamate excitotoxicity mediated by activated microglia/macrophage and astrocytes, which promote neuronal dysfunction, hasten neuronal death, and result in prominent cognitive deficits. My current research focus on the improvement of neuronal function and cognitive deficits by ameliorating neuroinflammation and excitotoxicity.

Selected Publications

  • Davila-Valencia I, Saad M, Olthoff G, Faulkner M, Charara M, Farnum A, Dysko RC, Zhang Z. Sex specific effects of buprenorphine on adult hippocampal neurogenesis and behavioral outcomes during the acute phase after pediatric traumatic brain injury in mice. Neuropharmacology. 1:245:109829. doi: 10.1016/j.neuropharm.2023.109829. (2024).
  • Faulkner MB, Rizk M, Bazzi Z, Dysko RC, Zhang Z. Sex-specific effects of buprenorphine on endoplasmic reticulum stress, abnormal protein accumulation, and cell loss after pediatric mild traumatic brain injury in mice. Neurotrauma Reports 2023:4(1):573-585. doi:10.1089/neur.2023.0051. PMCID: PMC10518695. (2023). 
  • Zhang F*, Zhang Z*, Alt J, Kambhampati SP, Sharma A, Singh S, Nance E, Rojas C, Rais R , Slusher BS, Kannan RM, Kannan S. “Dendrimer-enabled targeted delivery attenuates glutamate excitotoxicity and improves motor function in a rabbit model of cerebral palsy”. S0168-3659(23)00267-5. Journal of Controlled Release. doi: 10.1016/j.jconrel.2023.04.017. (2023). *, Co-first author. 
  • Sah N, Zhang Z, Chime AN, Fowler AY, Mendez-Trendler A, Sharma A, Rangaramanujam K, Slusher B, Kannan S. “Dendrimer conjugated glutamate carboxypeptidase II inhibitor restores microglial changes in a rabbit model of cerebral palsy”. Developmental Neuroscience. doi: 10.1159/000530389. (2023). 
  • Hamood Y, Abdullah M, El Ghoul H, Saad N, Dysko RC, Zhang Z. “Sex specific effects of buprenorphine on behavior, astrocytic opioid receptor expression and neuroinflammation after pediatric traumatic brain injury in mice”. Brain Behav Immun Health. 13;22:100469. doi: 10.1016/j.bbih.2022.100469. (2022)
  • Tallon C, Sharma A, Zhang Z, Thomas AG, Ng J, Zhu X, Donoghue A, Schulte M, Joe TR, Kambhampati SP, Sharma R, Liaw K, Kannan S, Kannan RM, Slusher BS. “Dendrimer-2PMPA Delays Muscle Function Loss and Denervation in a Murine Model of Amyotrophic Lateral Sclerosis”. Neurotherapeutics. 19(1):274-288. doi: 10.1007/s13311-021-01159-7. (2022).
  • Zhang Z, Nam HK, Crouch S, Hatch NE. “Tissue nonspecific alkalin phosphatase function in bone and muscle progenitor cells: control of mitochondrial respiration and ATP production”. Int. J. Mol. Sci. 22(3):1140. (2021).
  • Rizk M*, Vu J, Zhang Z. “Impact of pediatric traumatic brain injury on hippocampal neurogenesis.” Neural Regen Res. 16(5):926-933. Review (2021).
  • Arteaga O, Zhang Z, Khoury E, Sheldon RA, Sharma A, Zhang F, Slusher B, Kannan RM,  Kannan S, Ferriero DM. “Neuroprotective effects of a dendrimer-based glutamate carboxypeptidase inhibitor on superoxide dismutase transgenic mice after neonatal hypoxic-ischemic brain injury”. Neurobiol Dis. 148:105201. (2021).
  • Zhang Z, Lin YA, Kim SY, Su L, Liu J, Kannan RM, Kannan S. “Systemic dendrimer-drug nanomedicines for long-term treatment of mild-moderate cerebral palsy in a rabbit model.” J Neuroinflammation. 17(1):319. (2020).
  • Zhang Z, Ishrat S, O'Bryan M, Klein B, Saraswati M, Robertson CL, Kannan S. “Pediatric traumatic brain injury causes long-term deficits in adult hippocampal neurogenesis and cognition”. J Neurotrauma. 37(14):1656-1667. (2020).
  • Sharma A, Sharma R, Zhang Z, Liaw K, Kambhampati SP, Porterfield JE, Lin KC, DeRidder LB, Kannan S, Kannan RM. “Dense hydroxyl polyethylene glycol dendrimer targets activated glia in multiple CNS disorders”. Sci Adv. 22;6(4):eaay8514. (2020).
  • Bertrand SJ, Zhang Z, Patel R, O'Ferrell C, Punjabi NM, Kudchadkar SR, Kannan S. “Transient neonatal sleep fragmentation results in long-term neuroinflammation and cognitive impairment in a rabbit model.” Exp Neurol. 327:113212. (2020).
  • Sharma R, Kambhampati SP, Zhang Z, Sharma A, Chen S, Duh EI, Kannan S, Tso MOM, Kannan RM. “Dendrimer mediated targeted delivery of sinomenine for the treatment of acute neuroinflammation in traumatic brain injury.” J Control Release. 323:361-375. (2020).
  • Shu S, Zhang Z, Spicer D, Kulikowicz E, Hu K, Babapoor-Farrokhran S, Kannan S, Koehler RC, Robertson CL. “Administration of a 20-Hydroxyeicosatetraenoic Acid Synthesis Inhibitor Improves Outcome in a Rat Model of Pediatric Traumatic Brain Injury.” Dev Neurosci. 1-11. (2019).
  • Liaw K, Zhang Z, Kannan, S. “Neuronanotechnology for brain regeneration” Adv Drug Deliv Rev. 148:3-18. (2019).
  • Zhang Z, Rasmussen L, Saraswati M, Koehler RC, Robertson C, Kannan S. “Traumatic Injury Leads to Inflammation and Altered Tryptophan Metabolism in the Juvenile Rabbit Brain.” J Neurotrauma. 36:74–86. (2019).
  • Zhang Z, Narayan S, Su L, Al-Alawyat H, Liu J, Kannan S. “Cerebellar injury and impaired function in a rabbit model of maternal inflammation induced neonatal brain injury.” Neurobiol Learn Mem. 165:106901. (2018).
  • Sharma A, Liaw K, Sharma R, Zhang Z, Kannan S, Kannan RM. “Targeting Mitochondrial Dysfunction and Oxidative Stress in Activated Microglia using Dendrimer-Based Therapeutics.” Theranostics. 8(20):5529-5547. (2018).
  • Sharma R, Sharma A, Kambhampati SP, Reddy RR, Zhang Z, Cleland JL, Kannan S, Kannan RM. “Scalable synthesis and validation of PAMAM dendrimer-N-acetyl cysteine conjugate for potential translation.” Bioeng Transl Med. 3(2):87-101. (2018). 
  • Zhang Z, Jyoti A, Balakrishnan B, Williams M, Singh S, Chugani DC, Kannan S. "Trajectory of inflammatory and microglial activation markers in the postnatal rabbit brain following intrauterine endotoxin exposure." Neurobiol Dis. 111:153-162. (2017).
  • Nance E, Kambhampati SP, Smith ES, Zhang Z, Zhang F, Singh S, Johnston MV, Kannan RM, Blue ME, Kannan S. "Dendrimer-mediated delivery of N-acetyl cysteine to microglia in a mouse model of Rett syndrome." J Neuroinflammation. 14(1):252. (2017).
  • Sharma R, Kim S-Y, Sharma A, Zhang Z, Kambhampati SP, Kannan S, Kannan RM. "Activated microglia targeting dendrimer-minocycline conjugate as therapeutics for neuroinflammation" Bioconjugate Chemistry. 28(11):2874-2886. (2017).
  • Williams M, Zhang Z (co-first author), Nance E, Drewes J, Lesniak W, Singh S, Chugani D, Kannan RM, Graham D, Kannan S. "Maternal Inflammation Results in Altered Tryptophan Metabolism in Rabbit Placenta and Fetal Brain". Dev Neurosci. (2017).
  • Zhang Z, Bassam B, Thomas AG, Williams M, Liu J, Nance E, Rojas C, Slusher BS, Kannan S. "Maternal inflammation leads to impaired glutamate homeostasis and up-regulation of glutamate carboxypeptidase II in activated microglia in the fetal/newborn rabbit brain." Neurobiol Dis. 94:116-128. (2016).
  • Tucker EW, Pokkali S, Zhang Z, DeMarco VP, Klunk M, Smith ES, Ordonez AA, Penet MF, Bhujwalla Z, Jain SK, Kannan S. "Microglia activation in a pediatric rabbit model of tuberculous meningitis." Dis Model Mech. 9(12):1497-1506. (2016).
  • Zhang F, Nance E, Zhang Z, Jasty V, Kambhampati SP, Mishra MK, Burd I, Romero R, Kannan S, Kannan RM. "Surface functionality affects the biodistribution and microglia-targeting of intra-amniotically delivered dendrimers." J Control Release. pii: S0168-3659(16)30423-0. (2016).
  • Nance E, Zhang F, Mishra MK, Zhang Z, Kambhampati SP, Kannan RM, Kannan S. "Nanoscale effects in dendrimer-mediated targeting of neuroinflammation." Biomaterials. 101:96-107. (2016).
  • Zhang Z, Saraswati M, Koehler RC, Robertson CL, Kannan S. "A New Rabbit Model of Pediatric Traumatic Brain Injury." J Neurotrauma. 32(17):1369-79. (2015).
  • Zhang Z, van Praag H. "Maternal immune activation differentially impacts mature and adult-born hippocampal neurons in male mice." Brain, Behavior, and Immunity. 45:60-70. (2014).
  • Sun QQ, Zhang Z, Sun J, Nair A, Petrus D, Zhang C. "Functional and structural specific roles of activity-driven BDNF within circuits formed by single spiny stellate neurons of the barrel cortex." Front. Cell Neurosci. 8:372. (2014).
  • Jiao Y, Zhang Z (co-first author), Zhang C, Wang X, Sakata K, Lu B, Sun QQ. "A key mechanism underlying sensory experience-dependent maturation of neocortical GABAergic circuits in vivo." Proc Natl Acad Sci U S A. 108(29):12131-6. (2011).
  • Zhang Z, Sun QQ. "Development of NMDA NR2 subunits and their roles in critical period maturation of neocortical GABAergic interneurons." Dev Neurobiol. 71(3):221-45. (2011).
  • Zhang Z, Jiao YY, Sun QQ. "Developmental maturation of excitation and inhibition balance in principal neurons across four layers of somatosensory cortex." Neuroscience. 174:10-25. (2011).
  • Zhang Z, Sun QQ. "The balance between excitation and inhibition and functional sensory processing in the somatosensory cortex." Int Rev Neurobiol. 97:305-33. (2011).
  • Sun QQ, Zhang Z, "Whisker experience modulates long-term depression in neocortical γ-aminobutyric acidergic interneurons in barrel cortex." J Neurosci Res. 89(1):73-85. (2011).
  • Zhang Z, Bodznick D. "The importance of N-methyl-D-aspartate (NMDA) receptors in subtraction of electrosensory reafference in the dorsal nucleus of skates." J Exp Biol. 213(Pt 15):2700-9. (2010).
  • Sun QQ, Zhang Z, Jiao Y, Zhang C, Szabó G, Erdelyi F. "Differential metabotropic glutamate receptor expression and modulation in two neocortical inhibitory networks." J Neurophysiol. 101(5):2679-92. (2009).
  • Zhang Z, Bodznick D. "Plasticity in a cerebellar-like structure: suppressing reafference during episodic behaviors." J ExpBiol. 211(Pt 23):3720-8. (2008).
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