The Johns Hopkins Drug Abuse Research Center focuses on the Dynamics of Signaling by Molecular Messengers Relevant to Actions of Drugs of Abuse, an approach, which, over the years, has led to major insights into how novel proteins and small molecular messengers provide the neuronal signaling which underlies actions of psychotropic drugs. The ongoing and proposed projects of the four principal investigators interdigitate and are notably synergistic. Snyder addresses novel molecular messengers underlying drug actions including (1) NO/GAPDH nuclear signaling (2) Inositol hexakisphosphate kinase-2 (IP6K2) impacting cell death and neurotoxicity and (3) Actions of inositol polyphosphate multikinase (IPMK) that impact brain function. Worley deals with Rheb1 and mTOR signaling with a focus on (1) Translational mechanisms and transcriptional events regulated by mTOR, (2) The role of Rheb1 in myelination in the brain and (3) LanCL1 impacting signaling and growth factor dependent neuronal survival. The Dawsons address dynamics of poly (ADP-ribose) and how it regulates maladaptive stress responses that occur with psychotropic drug action. Specific areas of interest include (1) Iduna, a major novel protein regulating poly(ADP-ribose) disposition and cell survival, (2) Iduna influences upon epigenetic modifications (3) Influences of Iduna upon microRNA processing. Baraban deals with how the translin/trax RNAse complex regulates microRNA processing and responses to cocaine with a focus upon (1) Identifying physiologic targets of translin/trax, (2) Determining how deletion of translin interfaces with signaling pathways that are regulated by cocaine, and (3) Elucidating how striatal translin affects behavioral responses to cocaine.

Public Health Relevance

The Hopkins Drug Abuse Research Center focuses on molecular messengers whose actions are relevant to effects of abusable drugs. Discoveries by the Hopkins investigators have elucidated novel signaling systems that explain the neurotoxic effects of many drugs. These efforts have also uncovered new ways whereby cocaine exerts its psychoactivity. CENTER CHARACTERISTICS:

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Specialized Center (P50)
Project #
5P50DA000266-43
Application #
8663841
Study Section
Special Emphasis Panel (ZDA1-EXL-T (02))
Program Officer
Pollock, Jonathan D
Project Start
1975-06-20
Project End
2017-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
43
Fiscal Year
2014
Total Cost
$2,775,719
Indirect Cost
$1,062,312
Name
Johns Hopkins University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Mata, Ignacio F; Leverenz, James B; Weintraub, Daniel et al. (2016) GBA Variants are associated with a distinct pattern of cognitive deficits in Parkinson's disease. Mov Disord 31:95-102
Davis, Marie Y; Johnson, Catherine O; Leverenz, James B et al. (2016) Association of GBA Mutations and the E326K Polymorphism With Motor and Cognitive Progression in Parkinson Disease. JAMA Neurol 73:1217-1224
Cozzoli, Debra K; Courson, Justin; Rostock, Charlotte et al. (2016) Protein Kinase C Epsilon Activity in the Nucleus Accumbens and Central Nucleus of the Amygdala Mediates Binge Alcohol Consumption. Biol Psychiatry 79:443-51
Harraz, M M; Tyagi, R; Cortés, P et al. (2016) Antidepressant action of ketamine via mTOR is mediated by inhibition of nitrergic Rheb degradation. Mol Psychiatry 21:313-9
Guha, Prasun; Harraz, Maged M; Snyder, Solomon H (2016) Cocaine elicits autophagic cytotoxicity via a nitric oxide-GAPDH signaling cascade. Proc Natl Acad Sci U S A 113:1417-22
Scherer, Paul C; Ding, Yan; Liu, Zhiqing et al. (2016) Inositol hexakisphosphate (IP6) generated by IP5K mediates cullin-COP9 signalosome interactions and CRL function. Proc Natl Acad Sci U S A 113:3503-8
Fu, Xiuping; Shah, Aparna; Baraban, Jay M (2016) Rapid reversal of translational silencing: Emerging role of microRNA degradation pathways in neuronal plasticity. Neurobiol Learn Mem 133:225-32
Xu, Jin-Chong; Fan, Jing; Wang, Xueqing et al. (2016) Cultured networks of excitatory projection neurons and inhibitory interneurons for studying human cortical neurotoxicity. Sci Transl Med 8:333ra48
Mills, Kelly A; Mari, Zoltan; Bakker, Catherine et al. (2016) Gait function and locus coeruleus Lewy body pathology in 51 Parkinson's disease patients. Parkinsonism Relat Disord 33:102-106
Rao, Feng; Xu, Jing; Fu, Chenglai et al. (2015) Inositol pyrophosphates promote tumor growth and metastasis by antagonizing liver kinase B1. Proc Natl Acad Sci U S A 112:1773-8

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