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Deepak Srivastava

Deepak Srivastava

Professor of Molecular Neuroscience

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Overview

The formation, maintenance and the fine-tuning of synaptic connections between neurons is an essential part of brain function. These processes are modulated by a wide range of extracellular stimuli and are orchestrated through the regulation of synaptic proteins and key signalling pathways. Increasing evidence have also linked mutations or altered expression of synaptic proteins and signalling molecules are linked with neurodevelopmental and psychiatric disorders. Thus, understanding how synapses are formed and respond to different stimuli, and the exact role specific synaptic proteins play will help us better understand brain function in physiology as well as in specific disorders.

The main goal of the Srivastava Lab is to develop an in-depth understanding of the molecular mechanisms that underlie synaptic function in physiology, but also dysfunction in the context of neurodevelopment and psychiatric disorders. We specifically focus on elucidating the molecular mechanisms underlying the formation and remodelling of synapses, and how extracellular signals regulate these processes. Moreover, we are particularly interested in how genes associated with increased likelihood of developing neurodevelopmental and psychiatric disorders contribute to the control of synaptic structure, function and trafficking of proteins to and from synaptic compartments. To achieve this, we utilize cutting-edge technologies such as patient derived induced pluripotent stem cells (iPSCs) as well as advanced cellular imaging approaches. We work closely with basic and clinical colleagues as well as pharmaceutical companies to address these questions.

Selected publications

Erli F, Palmos AB, Raval P, Mukherjee J, Sellers KJ, Gatford NJF, Moss SJ, Brandon NJ, Penzes P, Srivastava DP (2020) Estradiol reverses excitatory synapse loss in a cellular model of neuropsychiatric disorders. Transl Psychiatry 10: 16

Warre-Cornish K, Perfect L, Nagy R, Duarte RRR, Reid MJ, Raval P, Mueller A, Evans AL, Couch A, Ghevaert C, McAlonan G, Loth E, Murphy D, Powell TR, Vernon AC, Srivastava DP, Price J (2020) Interferon-γ signaling in human iPSC-derived neurons recapitulates neurodevelopmental disorder phenotypes. Sci Adv 6: eaay9506

Duarte RRR, Bachtel ND, Côtel MC, Lee SH, Selvackadunco S, Watson IA, Hovsepian GA, Troakes C, Breen GD, Nixon DF, Murray RM, Bray NJ, Eleftherianos I, Vernon AC, Powell TR, Srivastava DP (2019) The Psychiatric Risk Gene NT5C2 Regulates Adenosine Monophosphate-Activated Protein Kinase Signaling and Protein Translation in Human Neural Progenitor Cells. Biol Psychiatry 86: 120-130

Deans PJM, Raval P, Sellers KJ, Gatford NJF, Halai S, Duarte RRR, Shum C, Warre-Cornish K, Kaplun VE, Cocks G, Hill M, Bray NJ, Price J, Srivastava DP (2017) Psychosis Risk Candidate ZNF804A Localizes to Synapses and Regulates Neurite Formation and Dendritic Spine Structure. Biol Psychiatry 82: 49-61