Xinyu Zhao, PhD Assistant Professor Department of Neurosciences

Zhao Lab

Education
1986-1990: BS, Biology (Biophysics), Beijing University (China)
1991-1997: PhD, Pharmacology, University of Washington (Seattle)
1998-2003: Research Associate/Sr.Research Associate, the Salk Institute for Biological Studies (La Jolla, CA).

Positions and Employment:
1991-1997 Graduate student research assistant, Department of Pharmacology, Univ of Washington, Seattle. Thesis Advisor: Dr. Krzysztof Palczewski.
1998-2003 Research Associate/Senior Research Associate, Laboratory of Genetics, the Salk Institute for Biological Studies, San Diego. Mentor: Dr. Fred H. Gage.
2003-date Assistant Professor, Department of Neurosciences, School of Medicine, University of New Mexico, Albuquerque, NM.

Honors and Societies:
1992-1996: Merck Pre-doctoral Fellowship
1998-1999: Neuroplasticity of Aging Training Grant Award
1999-2001: National Research Service Award NRSA
2001: The Salk Institute Society for Research Fellow Scientific Presentation Award
2003-2005: Rett Syndrome Research Foundation Research Grant Award
2003-2008 Two research grant awards from Rett Syndrome Research Foundation
2004 Travel Award for NIDA Mini-Symposia (San Diego, CA)
2005-2007 Research grant award from Oxnard Foundation
2005-2007 Two research grant awards from International Rett Syndrome Association
2007 Outstanding mentor for minority undergraduate student research.

Professional Societies:
1996-date Member of Society for Neuroscience (SFN)
2003-date Member of International Society for Stem Cell Research (ISSCR)
2007-date Member of the Epigenetic Society


Research Interest:
The research in our laboratory focuses on understanding the molecular and cellular pathways that regulate postnatal neurogenesis and neuronal maturation with the goal to apply this knowledge in treating neurological diseases and injuries.

Upon focal ischemia in adult brains, a large number of cells new cells migrate from the subventricular zone (SVZ) to the injured striatum, where it is understood that they potentially participate in neuronal regeneration. We have found that inflammatory cytokines, such as IL-6 and IL-1b can promote neuronal differentiation of adult neural stem cells (see Barkho et al 2006). We are currently investigating how adult neural stem cells behave in response to brain injuries and the underlying molecular mechanisms. Our long-term goal is to establish a molecular basis for utilizing adult neurogenesis and adult neural stem cells in brain repair. We are using a combination of cell biology, molecular biology, and brain imaging approaches in this project. This work is in collaboration with Dr. LA Cunningham (UNM Neuoscience), Dr. G Rosenberg (UNM Neurology). Our lab is a member of UNM BrAin Imaging center

Genomic DNA in eukaryotic cells exists in the form of chromatin, and is associated with histones and other chromatin proteins. The term “epigenetics” defines all meiotically and mitotically heritable changes in gene expression that are not coded in the DNA sequence itself, which only alter phenotype without changing genotype. Three systems, including DNA methylation, RNA-associated silencing, and histone modification, are used to initiate and sustain epigenetic modulation. Disturbance in one or another of these interacting systems can lead to inappropriate expression or silencing of genes, causing an array of multi-system disorders and neoplasias. We are interested in how epigenetic mechanisms regulate postnatal neurogenesis and neuronal maturation, and its implication in human neural developmental diseases and mental disorders, such as Rett Syndrome, Autism, Fragile X syndrome, fetal alcohol exposure, and depression (for a recent conference related to this). We use isolated neural stem cells, neurons, transgenic mice and classic behavioral mouse models. We are currently collaborating with UNM Center for Development and Disability, Dr. Andrea Allan (Neuroscience, UNM), Dr. Michael Wilson (Neuroscience, UNM), Dr. Fernando Venezuela (Neuroscience, UNM), and Dr. Peng Jin (Emory U).

Selected Publications:

1. Meng L, Zhao X, Wu H, Chen T: Response to 6,11-hexadecadiene Compounds in the eri-silk moth Philosamia cynthia ricini Donovan. 1990, Beijing University Science Journal.
2. Orellana SA, Amieux PS, Zhao X, and McKnight GS: Mutations in the catalytic subunit of the cAMP-dependent protein kinase interferes with holoenzyme formation without disrupting inhibition by protein kinase inhibitor. J. Biol. Chem. 1993; 268:6843-6.
3. Matthews RP, Guthrie CR, Wailes LM, Zhao X, Means AR, and McKnight GS: Calcium/calmodulin-dependent protein kinases type II and type IV differentially regulate CREB-dependent gene expression. Mol. Cel. Biol. 1994; 14: 6107-16.
4. Subbaraya I, Ruiz CC, Helekar BS, Zhao X, Gorczyca W, Pettenati MJ, Rao PN, Palczewski K, and Baehr W: Molecular characterization of human and mouse photoreceptor guanylate cyclase activating protein (GCAP) and chromosomal localization of the human gene. J. Biol. Chem. 1994; 269:31080-9.
5. Palczewski K, Subbaraya I, Gorczyca WA, Helekar BS, Ruiz CC, Ohguro H, Huang J, Zhao X, Crabb JW, Johnson RS, Walsh KA, Gray-Keller MP, Detwiler PB, and Baehr W: Molecular cloning and characterization of retinal photoreceptor guanylyl cyclase-activating protein. Neuron 1994; 13:395-404.
6. Zhao X, Palczewski K, and Ohguro H: Mechanism of rhodopsin phosphorylation. Biophysical Chem. 1995; 56:183-8.
7. Ohguro H, Rudnicka-Nawrot M, Buczylko J, Zhao X, Taylor JA, Walsh KA, and Palczewski K: Structural and enzymatic aspects of rhodopsin phosphorylation. J. Biol. Chem. 1996; 271:5215-24
8. Zhao X, Haeseleer FJ, Fariss RN, Huang J, Milam AH, and Palczewski K: Molecular cloning and localization of photoreceptor kinases. Vis. Neuroscience; 1997, 14: 225-32.
9. Cideciyan AV, Zhao X, Nielsen L, Khani SC, Jacobson SG and Palczewski K: Null mutation in rhodopsin kinase gene slows recovery kinetics of rod and cone phototransduction in man. Proc. Natl. Acad. Sci. USA, 1998, 95: 328-33.
10. Zhao X, Huang J, Khani SC, and Palczewski K: Molecular forms of rhodopsin kinase (GRK1). J. Biol. Chem. 1998, 273: 5124-31.
11. Zhao X, Yokoyama K, Whitten ME, Huang J, Gelb MH, and Palczewski K: A novel form of rhodopsin kinase from chicken retina and pineal gland. FEBS Lett. 1999 454 (1-2): 115-21.
12. Ueba T, Kaspar B, Zhao X, and Gage FH: Repression of human fibroblast growth factor 2 by a novel transcription factor. J. Biol. Chem. 1999, 274: 10382-7.
13. Zhao X, Lein ES, He A, Smith SC, Aston C, and Gage FH: Transcriptional Profiling Reveals Strict Boundaries between Hippocampal Subregions. J. Comp. Neurol.2001, 441(3):187-96
14. Zhao X, Gage FH. Expressing the central nervous system. Neurochem Res. 2002 27(10):953-4.
15. Zhao X, Ueba T, Christie BR, Barkho B, McConnell MJ, Nakashima K, Lein ES, Eadie B, Willhoite AR, Summers RG, Chun J., Lee K, and Gage FH. Methyl-CpG binding protein 1 is important for neurogenesis and genomic stability in adult neural stem cells. Proc. Natl. Acad. Sci. USA, 2003 100 (11): 6777-82..
16. Zhao X, Schaffer DV, Gage FH. Neurogenesis in adult brain: understanding the mechanism and regulation. Research and Perspective in Neurosciences. Foundation IPSEN (paris) (2003).
17. Farmer J, Zhao X, van Praag H, Wodtke K, Gage FH and Christie BR: Voluntary exercise reduces the threshold for the induction of long-term potentiation in the dentate gyrus in vivo. Neuroscience 2004, 124 (1): 71-9.
18. Lein E.S. Zhao X., Aston C. and Gage F.H. Defing a Molecular Anatomy of the Hippocampus using DNA Microarrays and High-Throughput In Situ Hybridization J. Neurosci. 2004 24(15): 3879-3889.
19. Van Praag H, Zhao X, and Gage FH. Neurogenesis in the adult mammalian brain. The Cognitive Neurosciences, M. Gazzaniga, Editor, (in press)
20. Zhao X, Lie DC, Gage FH. Adult-derived stem cells in treating Parkinson’s Diseases. Restorative therapies in Parkinson’s disease (2006, Springer, New York, ISBN-13:978-0387-29984-6).
21. Barkho B, Song H, and Gage FH, and Zhao X. Identification of astrocytes expressed factors that affect neural stem cell differentiation. Stem Cell and Dev 2006 15 (3): 407-421.
22. Smrt, RD. Eaves-Angenes J, Barkho BZ, Santistevan NJ, Aimone JB, Zhao C, Gage FH, and Zhao X . Mecp2 deficiency leads to delayed maturation and altered gene expression in hippocampal neurons. Neurobiol. of Diseases 2007 27(1):77-89.
23. Zhao X #, Pak C, Smrt RD, Jin P . “Epigenetics and Neural Developmental Disorders” Epigenetics 2007 2 (2): 130 – 138.
24. Li X, Barkho BZ, and Zhao X . Neural stem cells and neurogenic niche. (2008 Springer, Edited by Shi and Clegg) (in press)
25. Szulwach KE, Li X. Zhao X, and Peng Jin. MicroRNA and Stem Cell Epigenesis. Current Research and Perspectives in MicroRNAs (2008 Springer) (in press)
26. Li X, and Zhao X #. Epigenetic regulation of mammalian neural stem cells. Stem Cells and Dev 2008 (in press).
27. Allan AM, Liang X, Luo,Y, Pak C, LI, X, Szulwach KE, Chen D, Jin P, and Zhao X. The loss of methyl-CpG binding protein 1 leads to autism-like behavioral deficits 2008 Hum. Mol. Genet. 2008 17( 13): 2047-57.
28. Li X., Barkho BZ, Luo Y, Smrt RD, Liu C, Kuwabara T, Gage FH, and Zhao X. Epigenetic regulation of stem cell mitogen FGF-2 by Mbd1 in adult neural stem/progenitor cells. J. Biol. Chem. 2008 (in press)
29. Barkho BZ, Munoz A, Li, X, Li L, Cunningham LA, and Zhao X. Endogenous Matrix Metalloproteinase (MMP)-3 and MMP-9 Promote the Differentiation and Migration of Adult Neural Progenitor Cells in Response to Chemokines. Stem Cells 2008 (in press)
30. Barkho BZ and Zhao X. Neural stem cells response to Stroke and potential therapeutic applications Curr Stem Cells and Therapies (Invited review in preparation)
31. Smrt RD and Zhao X. Epigenetic regulation of neuronal dendritic spine development. Dendritic Spines: Biochemistry, Modeling and Properties. (Invited book chapter in preparation)

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