![Robert Lipsky](https://webarchive.library.unt.edu/eot2008/20080916131310im_/http://www.niaaa.nih.gov/NR/rdonlyres/E53E318C-C61F-464E-855B-1061B54785A5/0/RobertLipsky.jpg)
Robert Lipsky Ph.D., Acting Section Chief
National Institute on Alcohol Abuse and Alcoholism
National Institutes of Health
5625 Fishers Lane, Room 3S-04D:MSC 9412
Bethesda MD 20892-9412
telephone: +1 301.402.5591
fax: +1 301.480.2839
e-mail: rlipsky@mail.nih.govJoined LNG as a Henry Jackson fellow (Guest Researcher) in 1999, after previously directing a research lab at the American Red Cross. In June, 2001 he was selected by a search committee and awarded a Tenure-Track scientist position. Dr. Lipsky has developed an independent program on the role of neutrotrophins and neurotrophin receptors and excitatory amino acids in addiction and recovery and in affective illness, following a research pathway he had established prior to joining LNG. He discovered and “Functionated” a novel BDNF promoter polymorphism. He established a collaboration with John Rush and Dennis Charney to eludidate the pharmacogenetics of antidepressant response in the STAR*D dataset.
Mission Statement:Research conducted within the Section on Molecular Genetics focuses on the mechanisms by which neurons convert brief cellular changes into stable alterations in brain function. These transcriptional changes constitute a form of “molecular memory” Changes in intracellular calcium (Ca2+) brought about through L-type voltage-gated Ca2+channels and ionotropic glutamate receptors play an essential role in neuronal plasticity and play critical roles in neuronal responses to stress and injury. These receptors and other components of signal transduction pathways are central in maintaining the balance of inhibitory and excitatory pathways in brain are also likely to contribute to the brains response to drugs, including alcohol. Of particular interest are genes that may contribute to increasing vulnerability to alcohol dependence and co-morbid factors, such as anxiety and major depression. We use both human and animal model-based approaches to understanding the influence of genes on brain responses. Our focus is initially on two sets of genes: 1) genes selected on neurobiological grounds because of their known involvement in pathways thought to be important in mood disorders; and 2) genes implicated primarily by their positions within genomic regions implicated by genetic linkage or association studies of major mood disorders and related conditions. These two approaches are complimentary since the neurobiological candidates arise directly from existing etiologic hypotheses while the positional candidates may lead to the discovery of unexpected pathways. His lab has expertise in multiple areas of cellular and molecular neurobiology including functional assays for promoter activity, constructs, cloning, and RNA.
Current Staff:
Feng Tian, Ph.D., 301.443.3302 tianf@mail.nih.gov
![Feng Tian](https://webarchive.library.unt.edu/eot2008/20080916131310im_/http://www.niaaa.nih.gov/NR/rdonlyres/0440EABD-1A31-4A8C-971D-5CE3C5868549/0/FengTian.jpg) |
A contractor, who joined the Section of Molecular Genetics in 2005 to study molecular mechanisms regulating the release of BDNF by neurons. He has also been investigating the role of pre-pro BDNF isoforms in neuronal function. Recently, he performing differential mRNA expression experiments, using array-based and real-time RNA assays to discover alcohol-response genes.
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Xianzhang Hu, M.D.,
![Xianzhang Hu](https://webarchive.library.unt.edu/eot2008/20080916131310im_/http://www.niaaa.nih.gov/NR/rdonlyres/CC001D4E-C49D-4E4F-8F4D-6D022EEBD300/0/XianzhangHu.jpg) |
A psychiatrist, is a special volunteer who performs resequencing, functional genomics for sequence variants, and linkage. The focus of his work is the serotonin transporter where he discovered that the extensively studied HTTLPR is actually triallelic, quantitated allele effects – showing the alleles are actually codominant – and linked the high transcribing allele to OCD. Dr. Hu is expert in the design of 5’ exonuclease assays for problem loci, mRNA quantitation by RT-PCR and analyses of function with transfected reporter genes.
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Xueying Jiang, M.D., Ph.D., 301.443.3294 sjiang@mail.nih.gov
![Xueying Jiang](https://webarchive.library.unt.edu/eot2008/20080916131310im_/http://www.niaaa.nih.gov/NR/rdonlyres/37CB9C99-B01B-44FB-A506-53CBBAC3C44F/0/XueyingJiang.jpg) |
A contractor whose work centers on understanding the molecular mechanisms underlying activation-dependent transcriptional regulation of the BDNF gene (BDNF). She discovered that a sequence bridging the NMDA activation-responsive NF-κB and CRE sites in promoter 4 of BDNF contains a class B E-box that suppresses basal BDNF transcription. “Decoy” DNAs containing the E-box attenuated glutamate-mediated neuronal excitotoxicity and increased endogenous BDNF exon 4–specific mRNA levels. The basic helix–loop–helix (bHLH) transcription factor, Sharp-2, specifically binds this E-box region. Constitutively expressed Sharp-2 represses BDNF promoter 4–mediated transcription. Activating hippocampal neurons with NMDA rapidly displaced Sharp-2 from DNA but enhanced the occupancy of activated CREB and NF-κB in vivo. Taken together, these studies indicate that NMDA receptor activation of CREB and NF-κB overcomes bHLH protein–mediated repression of BDNF promoter 4, which promotes neuronal survival, and suggests a new role for Sharp-2.
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Selected Publications:
Lipsky RH, Jiang X, Xu K, Marko AJ, Neyer KM, Anderson TR, Marini AM: (2005) Genomics and variation of ionotropic glutamate receptors: implications for neuroplasticity. Amino Acids 28:169-175.
![PubMed Link](https://webarchive.library.unt.edu/eot2008/20080916131310im_/http://www.niaaa.nih.gov/NR/rdonlyres/292B3347-0EB0-4B4B-8200-108FAC652E2C/0/medline3.gif)
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Jiang X, Xu K, Hoberman J, Tian F, Marko AJ, Waheed J, Harris CR, Marini AM, M-A Enoch, Lipsky RH: (2005) BDNF and mood disorders: A novel functional promoter polymorphism and Val66Met are associated with anxiety but have opposing effects. Neuropsychopharmacology 30: 1353-1361.
Szeszko PS, Lipsky R, Mentschel C, Robinson D, Bilder RM, Kane JM, Goldman D, Malhotra AK: (2005) Brain-derived neurotrophic factor val66met polymorphism and volume of the hippocampal formation in healthy volunteers and schizophrenia. Mol Psychiatry 10:631-636
Jiang X, Tian F, Mearow K, Okagaki O, Lipsky RH, Marini AM: (2005) The excitoprotective effect of N-methyl-D-aspartate receptor is mediated by a BDNF autocrine loop in cultured hippocampal neurons. J Neurochem 94:713-722
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