Yuhai Zhao, PhD
Assistant Professor of Research
Neuroscience, Cell Biology and Anatomy
Neuroscience Center of Excellence
School of Medicine, LSU Health
2020 Gravier St, Suite D
New Orleans, LA 70112
Undergraduate: China Medical University, MBBS
Graduate: LSUHSC-NO, PhD
Current Academic Appointments:
Assistant professor/research LSUHSC-NO Neuroscience Center / Department of Cell Biology and Anatomy
Previous Post-Doctoral Fellowships:
University of Pittsburgh
University of Texas Health Sciences Center – Houston
Key words: Alzheimer;s disease, microRNA, neuroinflammation, neurogenesis, neuroprotection
Abundant evidence supports the idea that progressive up-regulation of complex pro-inflammatory signaling, Aβ42 peptide evolution, and loss of neurotrophic support underlie the initiation and propagation of Alzheimer's disease (AD). Micro RNA (miRNA)-mediated messenger RNA (mRNA) interference is a newly discovered genetic mechanism involved in the regulation of gene expression at the post-transcriptional level. AD affects specific areas of the brain, and mis-regulated miRNA expression is strongly linked to altered gene expression within these regions. In AD models, these same AD-enriched miRNAs induce specific pathological changes that are strikingly similar to those observed in AD brain. Evidence suggests that altered miRNA-mediated processing of specific mRNA populations triggers the pathogenic expression of genes that drive the AD process. The overall goal is to significantly move the miRNA in- AD field forward, and impact the scientific understanding of AD, by defining mechanistically how specific miRNAs induce molecular-genetic mechanisms that result in AD-type change.
Increases in the expression of a specific NF-κB-sensitive mir-146a and mir-34a down-regulates the abundance of several major mRNA targets, including complement factor H (CFH), and Trem2 that that are active regulators of the brain's innate immune system, inflammatory response and the generation of neurotrophic or neurotoxic amyloid peptides. The current project will explore the effects of alteration in mir-146a and mir-34a on target inflammatory genes expression and the subsequent impact and regulatory roles in AD.
Adult hippocampal neurogenesis is vital to the maintenance and plasticity of cognitive functions such as learning, memory and emotion. Mounting evidence suggests that loss of normal adult hippocampal neurogenesis is implicated in the cognitive impairment in AD. Restoration of hippocampal neurogenesis helps improve cognitive function in AD mice models. Wnt/β-catenin signaling pathway is an important regulating mechanism for the adult hippocampal neurogenesis. We have recently identified significant upregulation of a specific inhibitor of Wnt- β-catenin pathway in AD. In the meantime, through array analysis and algorithm calculation a miRNA linked to that inhibitor gene was also discovered. This research will focus on the interplay between miRNA and hippocampal neurogenesis and how this may be implicated in AD pathology and behavioral dysfunction.
Selected Peer-reviewed Publications:
Zhao Y, Cong L, Jaber V, Lukiw WJ. Microbiome-derived lipopolysaccharide enriched in the perinuclear region of the Alzheimer's disease brain, Front. Immunol. 2017
Zhao Y, Gibb SL, Zhao J, Moore AN, Hylin MJ, Menge T, Xue H, Baimukanova G, Potter D, Johnson EM, Holcomb JB, Cox CS Jr, Dash PK, Pati S. Wnt3a, a protein secreted by Mesenchymal Stem Cells is neuroprotective and promotes neurocognitive recovery following Traumatic Brain Injury. Stem Cells. 2016 Feb 3. doi: 10.1002/stem.2310.
Zhao Y, Pogue AI, Lukiw WJ. MicroRNA (miRNA) Signaling in the Human CNS in Sporadic Alzheimer's Disease (AD)-Novel and Unique Pathological Features. Int J Mol Sci. 2015 Dec 17;16(12):30105-16. doi: 10.3390/ijms161226223.
Gibb SL, Zhao Y, Potter D, Hylin MJ, Bruhn R, Baimukanova G, Zhao J, Xue H, Abdel-Mohsen M, Pillai SK, Moore AN, Johnson EM, Cox CS Jr, Dash PK, Pati S. TIMP3 Attenuates the Loss of Neural Stem Cells, Mature Neurons and Neurocognitive Dysfunction in Traumatic Brain Injury. Stem Cells. 2015 Dec;33(12):3530-44. doi: 10.1002/stem.2189.
Zhao Y, Bhattacharjee S, Dua P, Alexandrov PN, Lukiw WJ. microRNA-Based Biomarkers and the Diagnosis of Alzheimer's Disease. Front Neurol. 2015 Jul 13;6:162. doi: 10.3389/fneur.2015.00162. eCollection 2015
Zhao Y, Lukiw WJ. Microbiome-generated amyloid and potential impact on amyloidogenesis in Alzheimer's disease (AD). J Nat Sci. 2015 Jul;1(7). pii: e138.
Zhao Y, Hill JM, Bhattacharjee S, Percy ME, Pogue AI, Lukiw WJ. Aluminum-induced amyloidogenesis and impairment in the clearance of amyloid peptides from the central nervous system in Alzheimer's disease. Front Neurol. 2014 Sep 5;5:167. doi: 10.3389/fneur.2014.00167. eCollection 2014.
Zhao Y, Bhattacharjee S, Jones BM, Hill JM, Clement C, Sambamurti K, Dua P, Lukiw WJ. Beta-Amyloid Precursor Protein (βAPP) Processing in Alzheimer's Disease (AD) and Age-Related Macular Degeneration (AMD). Mol Neurobiol. 2015 Aug;52(1):533-44. doi: 10.1007/s12035-014-8886-3.
Zhao Y, Bhattacharjee S, Jones BM, Hill J, Dua P, Lukiw WJ. Regulation of neurotropic signaling by the inducible, NF-kB-sensitive miRNA-125b in Alzheimer's disease (AD) and in primary human neuronal-glial (HNG) cells. Mol Neurobiol. 2014 Aug;50(1):97-106. doi: 10.1007/s12035-013-8595-3.
Zhao Y, Lukiw WJ. TREM2 signaling, miRNA-34a and the extinction of phagocytosis. Front Cell Neurosci. 2013 Aug 29;7:131. doi: 10.3389/fncel.2013.00131. eCollection 2013.
Alexandrov PN, Zhao Y, Jones BM, Bhattacharjee S, Lukiw WJ. Expression of the phagocytosis-essential protein TREM2 is down-regulated by an aluminum-induced miRNA-34a in a murine microglial cell line. J Inorg Biochem. 2013 Nov;128:267-9. doi: 10.1016/j.jinorgbio.2013.05.010.
Bhattacharjee S, Zhao Y, Hill JM, Culicchia F, Kruck TP, Percy ME, Pogue AI, Walton JR, Lukiw WJ. Selective accumulation of aluminum in cerebral arteries in Alzheimer's disease (AD). J Inorg Biochem. 2013 Sep;126:35-7. doi: 10.1016/j.jinorgbio.2013.05.007.
Zhao Y, Bhattacharjee S, Jones BM, Dua P, Alexandrov PN, Hill JM, Lukiw WJ. Regulation of TREM2 expression by an NF-кB-sensitive miRNA-34a. Neuroreport. 2013 Apr 17;24(6):318-23. doi: 10.1097/WNR.0b013e32835fb6b0.
Menge T, Zhao Y*, Zhao J, Wataha K, Gerber M, Zhang J, Letourneau P, Redell J, Shen L, Wang J, Peng Z, Xue H, Kozar R, Cox CS Jr, Khakoo AY, Holcomb JB, Dash PK, Pati S. Mesenchymal stem cells regulate blood-brain barrier integrity through TIMP3 release after traumatic brain injury. Sci Transl Med. 2012 Nov 21;4(161):161ra150. doi: 10.1126/scitranslmed.3004660. * co-first author
Pati S, Gerber MH, Menge TD, Wataha KA, Zhao Y, Baumgartner JA, Zhao J, Letourneau PA, Huby MP, Baer LA, Salsbury JR, Kozar RA, Wade CE, Walker PA, Dash PK, Cox CS Jr, Doursout MF, Holcomb JB. Bone marrow derived mesenchymal stem cells inhibit inflammation and preserve vascular endothelial integrity in the lungs after hemorrhagic shock. PLoS One. 2011;6(9):e25171. doi: 10.1371/journal.pone.0025171.
Zhao Y, Calon F, Julien C, Winkler JW, Petasis NA, Lukiw WJ, Bazan NG. Docosahexaenoic acid-derived neuroprotectin D1 induces neuronal survival via secretase- and PPARγ-mediated mechanisms in Alzheimer's disease models. PLoS One. 2011 Jan 5;6(1):e15816. doi: 10.1371/journal.pone.0015816.
Cui JG, Li YY, Zhao Y, Bhattacharjee S, Lukiw WJ. Differential regulation of interleukin-1 receptor-associated kinase-1 (IRAK-1) and IRAK-2 by microRNA-146a and NF-kappaB in stressed human astroglial cells and in Alzheimer disease. J Biol Chem. 2010 Dec 10;285(50):38951-60. doi: 10.1074/jbc.M110.178848.
Hill JM, Zhao Y, Clement C, Neumann DM, Lukiw WJ. HSV-1 infection of human brain cells induces miRNA-146a and Alzheimer-type inflammatory signaling. Neuroreport. 2009 Oct 28;20(16):1500-5. doi: 10.1097/WNR.0b013e3283329c05.
Lukiw WJ, Zhao Y, Cui JG. An NF-kappaB-sensitive micro RNA-146a-mediated inflammatory circuit in Alzheimer disease and in stressed human brain cells. J Biol Chem. 2008 Nov 14;283(46):31315-22. doi: 10.1074/jbc.M805371200.
Zhao Y, Cui JG, Lukiw WJ. Reduction of sortilin-1 in Alzheimer hippocampus and in cytokine-stressed human brain cells. Neuroreport. 2007 Jul 16;18(11):1187-91.
Zhao Y, Cui JG, Lukiw WJ. Natural secretory products of human neural and microvessel endothelial cells: Implications in pathogenic "spreading" and Alzheimer's disease. Mol Neurobiol. 2006 Dec;34(3):181-92.
Alexandrov PN, Zhao Y, Pogue AI, Tarr MA, Kruck TP, Percy ME, Cui JG, Lukiw WJ. Synergistic effects of iron and aluminum on stress-related gene expression in primary human neural cells. J Alzheimers Dis. 2005 Nov;8(2):117-27; discussion 209-15.