ResearchN-methyl-D-aspartate (NMDA) subtype of glutamate receptors participates in the formation of neuronal plasticity and migration of developing neurons, and is the major component of glutamate toxicity on neurons. High level of NMDA receptor expression produced "smart mice', while low level of NMDA receptor is associated with schizophrenia in mice.
Genetic Regulation of the Glutamate Receptor Genes:
I am engaged in the genetic regulation of NMDA receptor genes during development and in a neuronal pattern. My previous and ongoing work includes isolation and analysis of the NR1 and NR2A promoters; growth factor regulation and developmental activation of these promoters. Currently, I am conducting experiments to clone novel transcription factors including single-stranded DNA binding proteins as transcriptional activator/repressor(s). I am also searching for key cis-elements and trans-factors important for developmental expression of the NMDA receptor genes. These studies may uncover factor(s) important for neuronal differentiation/maturation (supported by NIH R01 NS38077).
Signal Transduction and Nuclear Targets:
Both cell survival and death signals activate multiple pathways to modify selective nuclear proteins, such as, transcription factors, and regulate expression of relevant genes. However, only limited nuclear proteins were identified to be targets in such signaling. I am interested in identifying novel nuclear targets of cellular signaling. Currently, I am using the glutamate receptor promoters as a model to study the impact of growth factors on certain transcription factors (such as Sp proteins), and I am also using primary neuronal culture to evaluate the role of transcription factors (such as MEF2 proteins) in glutamate-induced apoptosis of neurons.
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Lab TechniquesMolecular biology & protein chemistry: all conventional techniques in molecular biology including cloning and subcloning; analysis of DNA, RNA, proteins (2-D gel, immunoblot, immunopreciptiation); RNA mapping; interactions between DNA-protein, protein-protein; reporter genes in eukaryotic cells; site-directed mutagenesis; recombinant defective adenovirus & sindbis virus; recombinant fusion proteins. Chromatin-immunoprecipitation, DNA methylation analysis, shRNA (RNAi) construction. Neuroscience and cell biology: immunocyto- and immunohistochemistry; cell culture (cell line and primary cells); in situ hybridization histochemistry; signal transduction analysis.
PublicationsBai, G. & Kusiak, J.W. (1995) Functional analysis of the proximal 5'-flanking region of the N-methyl-D-aspartate receptor subunit gene, NMDAR1 J. Biol. Chem. 270:7737-7744
Nemer, M., Stuebing, E.W., Bai, G. & Parker, H. R. (1995) Spatial regulation of SpMTA metallothionein gene expression in sea urchin embryos by an intron 1 region. Mech. Dev 50:131-7
Liang, Y., Bai, G., Doliba, N., Buettger, C., Wang, L-q., Berner, D.K. & Matschinsky, F.M. (1996) Glucose metabolism and insulin release in mouse b HC9 cells-as model for wild type pancreatic b-cells. Am. J. Physiol. 270:E846-57
Bai, G. & Kusiak, J.W. (1997) Nerve growth factor up-regulates the rat N-methyl-D-aspartate receptor 1 promoter in PC12 cells. J. Biol. Chem. 272:5936-42
Bai, G., Norten, D. Prenger, M. & Kusiak, J.W. (1998) Single-stranded DNA binding proteins and NRSF participate in the cell-specific transcription control of the NMDAR1 gene. J. Biol. Chem. 273:1086-91
Krainc, D.,Bai, G., Okamoto, S-i, Carles, M., Kusiak, J.W., Brent, R. & Lipton, S.A.(1998) Synergistic activation of the N-methyl-D-aspartate receptor subunit 1 promoter by myocyte enhancer factor 2C and Sp1. J. Biol. Chem. 273:26218-24
Bai, G. & Lipton, S.A.(1998) Aberrant RNA splicing in sporadic amyotrophic lateral sclerosis. Neuron 20:363-6
Chio, Y-B., Tenneti, L., Le, D., Ortiz, J., Bai, G., Chen, H-S. V. & Lipton, S.A. (2000) Molecular basis of NMDA receptor modulation by S-nitrosylation. Nature Neurosci. 3:15-21
Liu, A.G., Prenger, M.S., Norton, D.D., Mei, L., John W. Kusiak, J.W. & Bai, G. (2001) NGF uses Ras/Erk and phosphatidylinositol 3-kinase cascades to upregulate the N-methyl-D-aspartate receptor 1 promoter. J. Biol. Chem. 276:45372-9
Liu, A.G., Zhuang, Z-Y, Hoffman, P.W. & Bai, G. (2003) Functional analysis of the rat N-methyl-D-aspartate receptor 2A promoter: multiple transcription start points, positive regulation by Sp factors and translational regulation. J. Biol. Chem. 278:26423-34
Bai, G, Zhuang, Z-Y, Liu, A.G. & Hoffman, P.W. (2003) The role of the RE1 element in activation of the NR1 promoter during neuronal differentiation. J. Neurochem. 86:992-1005
Liu, A.G., Hoffman, P.W., Lu, W.W., & Bai, G. (2004) NF-kB site interacts with Sp factors and upregulates the NR1 promoter during neuronal differentiation. J. Biol. Chem. 279:17449-58 Personal HistoryI received an M.D. and a M.S. in Biochemistry from the 4th Military Medical College in China, and a Ph.D. in Pharmacology from University of Ulm in the former West Germany. I finished two terms of post-doctoral training with Dr. Benjamin Weiss at Medical College of Pennsylvania in Molecular Neuroscience and with Dr. Martin Nemer at Fox Chase Cancer Center in Molecular Developmental Biology. I spent 5 years with NIH as a Senior Staff Fellow, and 3 years with Brigham & Women's Hospital/Harvard Medical School as a junior faculty before I joined the faculty of UMAB Dental School in 2000. Laboratory PersonnelAnguo Liu, M.D., Ph.D., Post-doctoral Fellow
Peter Hoffman, Ph.D., Visiting Professor, College of Notre Dame of Maryland. Back to All Faculty |