Zhen Zhao, PhD

Title(s)Assistant Professor of Physiology & Neuroscience
SchoolKeck School of Medicine of Usc
AddressZNI 207, 1501 San Pablo Street
Health Sciences Campus
Los Angeles CA 90033
Phone+1 323 442 2484
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    Other Positions
    Title(s)Director, Cell Engineering & Regeneration Core

    Collapse Biography 
    Collapse Education and Training
    Fudan University, Shanghai, ChinaB.S.06/2001Biological Sciences
    University of Southern California, Los Angeles, CAPh.D.12/2009Neuroscience
    Collapse Awards and Honors
    Alzheimer’s Association 2015  - 2017NIRG-15-363387
    NIA/USC ADRC2016  - 2017ADRC Pilot
    L.K. Whittier Foundation2017  - 2018L.K. Whittier Foundation Translational Research Project
    Cure Alzheimer’s Fund2015  - 2019Cure Alzheimer’s Fund
    NIH/NIA2019  - 2024R01AG061288
    NIH/NIA2019  - 2021R21AG063287
    NIH/NINDS2019  - 2014R01NS110687
    BrightFocus Foundation2019  - 2022BrightFocus Foundation

    Collapse Overview 
    Collapse Overview
    Research Directions

    i) To search for the genetic causes of vascular cognitive impairment and dementia
    50 million people worldwide are now suffering from dementia; however, the exact causes remain elusive. Vascular Cognitive Impairment and Dementia (VCID) due to cerebrovascular diseases and pathologies represents 20~40% of the dementia cases, and largely overlaps with AD in terms of pathologies and pathogenic factors. Recently, we have been working with two groups of genetic risk factors that are vascular residents but can either predispose individual to cerebrovascular diseases or strongly modify the course of AD and VCID, such as platelet-derived growth factor receptor beta (PDGFRß), LRP1 and PICALM. Although this is just the first peek through the looking glass, yet our finding has brought new insight into the genetic causes of VCID and AD, suggesting that a better understanding the etiology and pathogenesis of AD and VICD, especially decoding the common genetic causes may help us redefining a subset of cases, and land more effective therapeutics for them in the near future.

    ii) To study the molecular mechanism of the receptor-mediated transport at the blood-brain barrier
    Receptor-mediated transcytosis (RMT) provides a major clearance pathway for Aß at the BBB, by flushing Aß out from brain to circulation. However, the understanding of this unique system remains limited, particularly regarding the molecular machinery which drives the cargos through multiple transcytosis events, including receptor-mediated endocytosis, intracellular trafficking, and exocytosis, as well as avoids the degradation pathway through late endosomes and lysosomes. Impaired vascular Aß clearance leads to elevated brain Aß level and exacerbates AD pathology. Piling evidence indicates that the alteration in the RMT system, particularly abnormal expression of AD vascular risk genes in the cerebral vasculature, contributes to pathogenesis. By studying the PICALM-dependent transvascular RMT machinery, we also hope to identify new key molecular targets of the BBB, which can be or manipulated pharmacologically or by adeno-associated virus (AAV)-mediated gene delivery, for more effective CNS drug delivery across the BBB.

    iii) To examine the crosstalk between the cells within the neurovascular unit
    Structural and functional brain connectivity, synaptic activity and information processing require highly coordinated signal transduction between different cell types within the neurovascular unit (NVU). The cells of the NVU are not just adjacently located and structurally connected; they communicated with each other vigorously via different signaling modules in order to function in orchestration. Such crosstalk is achieved by various cellular mechanisms, including but not limited to signaling receptors and channels, microRNA-containing exosomal vehicles (EVs) and gap junction-mediated direct exchange of small molecules. Neurovascular congruency is essential for the proper patterning of the CNS during development and neurovascular interaction is critical for normal brain functions, while its dysfunctions contribute to the pathogenesis of CNS injuries and neurodegenerative diseases, such as stroke and Alzheimer’s disease. We expect to provide evidence of functional pericyte–neuron crosstalk for brain health and functions, as well as pericyte contribution to brain’s innate immunity during CNS diseases or viral infections.

    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help. to make corrections and additions.
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    Altmetrics Details PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Acetylated tau: A missing link between head injury and dementia. Med (N Y). 2021 06 11; 2(6):637-639. Zhao Z, Zlokovic BV. PMID: 35590136.
      View in: PubMed   Mentions:    Fields:    Translation:Humans
    2. Endothelial Tip Cell Finds Its Way with Piezo1. Neuron. 2020 10 14; 108(1):5-7. Zhao Z, Zlokovic BV. PMID: 33058766; PMCID: PMC7737505.
      View in: PubMed   Mentions: 1     Fields:    Translation:AnimalsCells
    3. Therapeutic TVs for Crossing Barriers in the Brain. Cell. 2020 07 23; 182(2):267-269. Zhao Z, Zlokovic BV. PMID: 32707092; PMCID: PMC7737504.
      View in: PubMed   Mentions: 5     Fields:    Translation:HumansAnimals
    4. Blood-Brain Barrier: From Physiology to Disease and Back. Physiol Rev. 2019 01 01; 99(1):21-78. Sweeney MD, Zhao Z, Montagne A, Nelson AR, Zlokovic BV. PMID: 30280653; PMCID: PMC6335099.
      View in: PubMed   Mentions: 716     Fields:    Translation:HumansAnimalsCells
    5. Blood-brain barrier-associated pericytes internalize and clear aggregated amyloid-β42 by LRP1-dependent apolipoprotein E isoform-specific mechanism. Mol Neurodegener. 2018 10 19; 13(1):57. Ma Q, Zhao Z, Sagare AP, Wu Y, Wang M, Owens NC, Verghese PB, Herz J, Holtzman DM, Zlokovic BV. PMID: 30340601; PMCID: PMC6194676.
      View in: PubMed   Mentions: 109     Fields:    Translation:HumansAnimalsCells
    6. Pericyte degeneration causes white matter dysfunction in the mouse central nervous system. Nat Med. 2018 03; 24(3):326-337. Montagne A, Nikolakopoulou AM, Zhao Z, Sagare AP, Si G, Lazic D, Barnes SR, Daianu M, Ramanathan A, Go A, Lawson EJ, Wang Y, Mack WJ, Thompson PM, Schneider JA, Varkey J, Langen R, Mullins E, Jacobs RE, Zlokovic BV. PMID: 29400711; PMCID: PMC5840035.
      View in: PubMed   Mentions: 183     Fields:    
    7. Experimental chronic cerebral hypoperfusion results in decreased pericyte coverage and increased blood-brain barrier permeability in the corpus callosum. J Cereb Blood Flow Metab. 2019 02; 39(2):240-250. Liu Q, Radwanski R, Babadjouni R, Patel A, Hodis DM, Baumbacher P, Zhao Z, Zlokovic B, Mack WJ. PMID: 29192539; PMCID: PMC6365610.
      View in: PubMed   Mentions: 41     Fields:    Translation:AnimalsCells
    8. Alzheimer's disease: A matter of blood-brain barrier dysfunction? J Exp Med. 2017 Nov 06; 214(11):3151-3169. Montagne A, Zhao Z, Zlokovic BV. PMID: 29061693; PMCID: PMC5679168.
      View in: PubMed   Mentions: 291     Fields:    Translation:HumansAnimals
    9. Can adjunctive therapies augment the efficacy of endovascular thrombolysis? A potential role for activated protein C. Neuropharmacology. 2018 05 15; 134(Pt B):293-301. Amar AP, Sagare AP, Zhao Z, Wang Y, Nelson AR, Griffin JH, Zlokovic BV. PMID: 28923278; PMCID: PMC5857404.
      View in: PubMed   Mentions: 13     Fields:    Translation:HumansAnimals
    10. Remote control of BBB: A tale of exosomes and microRNA. Cell Res. 2017 07; 27(7):849-850. Zhao Z, Zlokovic BV. PMID: 28674430; PMCID: PMC5518990.
      View in: PubMed   Mentions: 36     Fields:    Translation:HumansAnimalsCells
    11. Regional early and progressive loss of brain pericytes but not vascular smooth muscle cells in adult mice with disrupted platelet-derived growth factor receptor-β signaling. PLoS One. 2017; 12(4):e0176225. Nikolakopoulou AM, Zhao Z, Montagne A, Zlokovic BV. PMID: 28441414; PMCID: PMC5404855.
      View in: PubMed   Mentions: 62     Fields:    Translation:AnimalsCells
    12. Pericyte degeneration leads to neurovascular uncoupling and limits oxygen supply to brain. Nat Neurosci. 2017 Mar; 20(3):406-416. Kisler K, Nelson AR, Rege SV, Ramanathan A, Wang Y, Ahuja A, Lazic D, Tsai PS, Zhao Z, Zhou Y, Boas DA, Sakadžic S, Zlokovic BV. PMID: 28135240; PMCID: PMC5323291.
      View in: PubMed   Mentions: 231     Fields:    Translation:AnimalsCells
    13. 3K3A-activated protein C stimulates postischemic neuronal repair by human neural stem cells in mice. Nat Med. 2016 09; 22(9):1050-5. Wang Y, Zhao Z, Rege SV, Wang M, Si G, Zhou Y, Wang S, Griffin JH, Goldman SA, Zlokovic BV. PMID: 27548576; PMCID: PMC5215920.
      View in: PubMed   Mentions: 57     Fields:    Translation:HumansAnimalsCells
    14. Zika Virus NS4A and NS4B Proteins Deregulate Akt-mTOR Signaling in Human Fetal Neural Stem Cells to Inhibit Neurogenesis and Induce Autophagy. Cell Stem Cell. 2016 11 03; 19(5):663-671. Liang Q, Luo Z, Zeng J, Chen W, Foo SS, Lee SA, Ge J, Wang S, Goldman SA, Zlokovic BV, Zhao Z, Jung JU. PMID: 27524440; PMCID: PMC5144538.
      View in: PubMed   Mentions: 261     Fields:    Translation:HumansAnimalsCells
    15. Accelerated pericyte degeneration and blood-brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer's disease. J Cereb Blood Flow Metab. 2016 Jan; 36(1):216-27. Halliday MR, Rege SV, Ma Q, Zhao Z, Miller CA, Winkler EA, Zlokovic BV. PMID: 25757756; PMCID: PMC4758554.
      View in: PubMed   Mentions: 305     Fields:    Translation:HumansCells
    16. Establishment and Dysfunction of the Blood-Brain Barrier. Cell. 2015 Nov 19; 163(5):1064-1078. Zhao Z, Nelson AR, Betsholtz C, Zlokovic BV. PMID: 26590417; PMCID: PMC4655822.
      View in: PubMed   Mentions: 672     Fields:    Translation:HumansAnimalsCells
    17. Truncating mutation in the autophagy gene UVRAG confers oncogenic properties and chemosensitivity in colorectal cancers. Nat Commun. 2015 Aug 03; 6:7839. He S, Zhao Z, Yang Y, O'Connell D, Zhang X, Oh S, Ma B, Lee JH, Zhang T, Varghese B, Yip J, Dolatshahi Pirooz S, Li M, Zhang Y, Li GM, Ellen Martin S, Machida K, Liang C. PMID: 26234763; PMCID: PMC4526116.
      View in: PubMed   Mentions: 43     Fields:    Translation:HumansAnimalsCells
    18. Central role for PICALM in amyloid-β blood-brain barrier transcytosis and clearance. Nat Neurosci. 2015 Jul; 18(7):978-87. Zhao Z, Sagare AP, Ma Q, Halliday MR, Kong P, Kisler K, Winkler EA, Ramanathan A, Kanekiyo T, Bu G, Owens NC, Rege SV, Si G, Ahuja A, Zhu D, Miller CA, Schneider JA, Maeda M, Maeda T, Sugawara T, Ichida JK, Zlokovic BV. PMID: 26005850; PMCID: PMC4482781.
      View in: PubMed   Mentions: 218     Fields:    Translation:HumansAnimalsCells
    19. GLUT1 reductions exacerbate Alzheimer's disease vasculo-neuronal dysfunction and degeneration. Nat Neurosci. 2015 Apr; 18(4):521-530. Winkler EA, Nishida Y, Sagare AP, Rege SV, Bell RD, Perlmutter D, Sengillo JD, Hillman S, Kong P, Nelson AR, Sullivan JS, Zhao Z, Meiselman HJ, Wendy RB, Soto J, Abel ED, Makshanoff J, Zuniga E, De Vivo DC, Zlokovic BV. PMID: 25730668; PMCID: PMC4734893.
      View in: PubMed   Mentions: 284     Fields:    Translation:Animals
    20. Blood-brain barrier breakdown in the aging human hippocampus. Neuron. 2015 Jan 21; 85(2):296-302. Montagne A, Barnes SR, Sweeney MD, Halliday MR, Sagare AP, Zhao Z, Toga AW, Jacobs RE, Liu CY, Amezcua L, Harrington MG, Chui HC, Law M, Zlokovic BV. PMID: 25611508; PMCID: PMC4350773.
      View in: PubMed   Mentions: 898     Fields:    Translation:HumansCells
    21. Negative regulation of NF-κB activity by brain-specific TRIpartite Motif protein 9. Nat Commun. 2014 Sep 05; 5:4820. Shi M, Cho H, Inn KS, Yang A, Zhao Z, Liang Q, Versteeg GA, Amini-Bavil-Olyaee S, Wong LY, Zlokovic BV, Park HS, García-Sastre A, Jung JU. PMID: 25190485; PMCID: PMC4157316.
      View in: PubMed   Mentions: 39     Fields:    Translation:HumansAnimalsCells
    22. Blood-brain barrier: a dual life of MFSD2A? Neuron. 2014 May 21; 82(4):728-30. Zhao Z, Zlokovic BV. PMID: 24853933; PMCID: PMC4114515.
      View in: PubMed   Mentions: 32     Fields:    Translation:Animals
    23. Blood-spinal cord barrier disruption contributes to early motor-neuron degeneration in ALS-model mice. Proc Natl Acad Sci U S A. 2014 Mar 18; 111(11):E1035-42. Winkler EA, Sengillo JD, Sagare AP, Zhao Z, Ma Q, Zuniga E, Wang Y, Zhong Z, Sullivan JS, Griffin JH, Cleveland DW, Zlokovic BV. PMID: 24591593; PMCID: PMC3964055.
      View in: PubMed   Mentions: 117     Fields:    Translation:HumansAnimalsCells
    24. UVRAG is required for virus entry through combinatorial interaction with the class C-Vps complex and SNAREs. Proc Natl Acad Sci U S A. 2014 Feb 18; 111(7):2716-21. Pirooz SD, He S, Zhang T, Zhang X, Zhao Z, Oh S, O'Connell D, Khalilzadeh P, Amini-Bavil-Olyaee S, Farzan M, Liang C. PMID: 24550300; PMCID: PMC3932887.
      View in: PubMed   Mentions: 20     Fields:    Translation:HumansAnimalsCells
    25. Activated protein C analog protects from ischemic stroke and extends the therapeutic window of tissue-type plasminogen activator in aged female mice and hypertensive rats. Stroke. 2013 Dec; 44(12):3529-36. Wang Y, Zhao Z, Chow N, Rajput PS, Griffin JH, Lyden PD, Zlokovic BV. PMID: 24159062; PMCID: PMC3912991.
      View in: PubMed   Mentions: 34     Fields:    Translation:Animals
    26. PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential interactions with the ER tether and the beclin 1 complex. Nat Cell Biol. 2013 Oct; 15(10):1206-1219. He S, Ni D, Ma B, Lee JH, Zhang T, Ghozalli I, Pirooz SD, Zhao Z, Bharatham N, Li B, Oh S, Lee WH, Takahashi Y, Wang HG, Minassian A, Feng P, Deretic V, Pepperkok R, Tagaya M, Yoon HS, Liang C. PMID: 24056303; PMCID: PMC3805255.
      View in: PubMed   Mentions: 57     Fields:    Translation:HumansAnimalsCells
    27. CNP/cGMP signaling regulates axon branching and growth by modulating microtubule polymerization. Dev Neurobiol. 2013 Sep; 73(9):673-87. Xia C, Nguyen M, Garrison AK, Zhao Z, Wang Z, Sutherland C, Ma L. PMID: 23420620; PMCID: PMC4229251.
      View in: PubMed   Mentions: 12     Fields:    Translation:AnimalsCells
    28. An activated protein C analog stimulates neuronal production by human neural progenitor cells via a PAR1-PAR3-S1PR1-Akt pathway. J Neurosci. 2013 Apr 03; 33(14):6181-90. Guo H, Zhao Z, Yang Q, Wang M, Bell RD, Wang S, Chow N, Davis TP, Griffin JH, Goldman SA, Zlokovic BV. PMID: 23554499; PMCID: PMC3707621.
      View in: PubMed   Mentions: 40     Fields:    Translation:HumansAnimalsCells
    29. Activated protein C analog promotes neurogenesis and improves neurological outcome after focal ischemic stroke in mice via protease activated receptor 1. Brain Res. 2013 Apr 24; 1507:97-104. Wang Y, Zhao Z, Chow N, Ali T, Griffin JH, Zlokovic BV. PMID: 23438513; PMCID: PMC3739836.
      View in: PubMed   Mentions: 18     Fields:    Translation:Animals
    30. Pericyte loss influences Alzheimer-like neurodegeneration in mice. Nat Commun. 2013; 4:2932. Sagare AP, Bell RD, Zhao Z, Ma Q, Winkler EA, Ramanathan A, Zlokovic BV. PMID: 24336108; PMCID: PMC3945879.
      View in: PubMed   Mentions: 338     Fields:    Translation:AnimalsCells
    31. UVRAG: at the crossroad of autophagy and genomic stability. Autophagy. 2012 Sep; 8(9):1392-3. Zhao Z, Ni D, Ghozalli I, Pirooz SD, Ma B, Liang C. PMID: 22885520; PMCID: PMC3442888.
      View in: PubMed   Mentions: 12     Fields:    Translation:AnimalsCells
    32. A dual role for UVRAG in maintaining chromosomal stability independent of autophagy. Dev Cell. 2012 May 15; 22(5):1001-16. Zhao Z, Oh S, Li D, Ni D, Pirooz SD, Lee JH, Yang S, Lee JY, Ghozalli I, Costanzo V, Stark JM, Liang C. PMID: 22542840; PMCID: PMC3356442.
      View in: PubMed   Mentions: 57     Fields:    Translation:HumansCells
    33. Measurement of γHV68 infection in mice. J Vis Exp. 2011 Nov 22; (57). Pirooz SD, Lee JH, Zhao Z, Ni D, Oh S, Liang C. PMID: 22127138; PMCID: PMC3308616.
      View in: PubMed   Mentions:    Fields:    Translation:AnimalsCells
    34. Anti-autophagic Bcl-2: Not just an innocent bystander. Autophagy. 2011 Feb; 7(2):231-2. Oh S, Pirooz SD, Ni D, Zhao Z, Liang C. PMID: 21099349; PMCID: PMC3679092.
      View in: PubMed   Mentions: 1     Fields:    Translation:Humans
    35. Regulation of axonal development by natriuretic peptide hormones. Proc Natl Acad Sci U S A. 2009 Oct 20; 106(42):18016-21. Zhao Z, Ma L. PMID: 19805191; PMCID: PMC2764873.
      View in: PubMed   Mentions: 33     Fields:    Translation:AnimalsCells
    36. The transduction channel TRPM5 is gated by intracellular calcium in taste cells. J Neurosci. 2007 May 23; 27(21):5777-86. Zhang Z, Zhao Z, Margolskee R, Liman E. PMID: 17522321; PMCID: PMC6672777.
      View in: PubMed   Mentions: 97     Fields:    Translation:HumansAnimalsCells
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