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:

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Specialized Center (P50)
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Study Section
Special Emphasis Panel (ZDA1)
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Pollock, Jonathan D
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Johns Hopkins University
Schools of Medicine
United States
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Harraz, Maged M; Snyder, Solomon H (2017) Antidepressant Actions of Ketamine Mediated by the Mechanistic Target of Rapamycin, Nitric Oxide, and Rheb. Neurotherapeutics 14:728-733
Park, Alan Jung; Havekes, Robbert; Fu, Xiuping et al. (2017) Learning induces the translin/trax RNase complex to express activin receptors for persistent memory. Elife 6:
Fu, Chenglai; Xu, Jing; Cheng, Weiwei et al. (2017) Neuronal migration is mediated by inositol hexakisphosphate kinase 1 via ?-actinin and focal adhesion kinase. Proc Natl Acad Sci U S A 114:2036-2041
Paul, Bindu D; Snyder, Solomon H (2017) Gasotransmitter hydrogen sulfide signaling in neuronal health and disease. Biochem Pharmacol :
Dawson, Ted M; Dawson, Valina L (2017) Mitochondrial Mechanisms of Neuronal Cell Death: Potential Therapeutics. Annu Rev Pharmacol Toxicol 57:437-454
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 133:225-232
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
Rosenthal, Liana S; Drake, Daniel; Alcalay, Roy N et al. (2016) The NINDS Parkinson's disease biomarkers program. Mov Disord 31:915-23
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
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

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