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Deepak P Srivastava

Deepak P Srivastava

Lecturer in the Neurobiology of Schizophrenia

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Overview

Research in the Srivastava lab (aka the Neuronal Circuitry and Neurodevelopmental Disorders Group (NCND)), seeks to understand the mechanisms that regulate excitatory synapse structure and function. We are focus on elucidating the molecular mechanisms underlying the remodelling of neuronal connectivity, with a particular emphasis on how disease-risk genes control synaptic structure, function and trafficking of proteins to and from synaptic compartments. As aberrant neuronal circuitry is a fundamental property of many neurodevelopmental and psychiatric disorders, understanding the mechanisms that regulate connectivity is critical in understanding of these disease as well as for the development of novel therapeutic strategies. To address these questions, we employ a multi-disciplinary approach, including molecular and biochemical techniques, as well as advanced and cutting edge imaging techniques. This allows us to examine the dynamic nature of synaptic morphology and proteins. Furthermore, we use primary cell cultures, animal models, human neural stem cell and patient derived pluripotent stem cells models to model the role of risk-proteins on synapse structure and function.

Selected publications

Kathuria A, Nowosiad P, Jagasia R, Aigner S, Taylor RD, Andreae LC, Gatford NJF, Lucchesi W, Srivastava DP, Price J (2018) Stem cell-derived neurons from autistic individuals with SHANK3 mutation show morphogenetic abnormalities during early development. Mol Psychiatry 23: 735-746

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
Duarte RRR, Troakes C, Nolan M, Srivastava DP, Murray RM, Bray NJ (2016) Genome-wide significant schizophrenia risk variation on chromosome 10q24 is associated with altered cis-regulation of BORCS7, AS3MT, and NT5C2 in the human brain. Am J Med Genet B Neuropsychiatr Genet 171: 806-14
Sellers KJ, Erli F, Raval P, Watson IA, Chen D, Srivastava DP (2015) Rapid modulation of synaptogenesis and spinogenesis by 17?-estradiol in primary cortical neurons. Front Cell Neurosci 9: 137
Jones KA, Eng AG, Raval P, Srivastava DP, Penzes P (2014) Scaffold protein X11? interacts with kalirin-7 in dendrites and recruits it to Golgi outposts. J Biol Chem 289: 35517-29
VanLeeuwen JE, Rafalovich I, Sellers K, Jones KA, Griffith TN, Huda R, Miller RJ, Srivastava DP, Penzes P (2014) Coordinated nuclear and synaptic shuttling of afadin promotes spine plasticity and histone modifications. J Biol Chem 289: 10831-42
Srivastava DP, Woolfrey KM, Penzes P (2013) Insights into rapid modulation of neuroplasticity by brain estrogens. Pharmacol Rev 65: 1318-50
Srivastava DP, Evans PD (2013) G-protein oestrogen receptor 1: trials and tribulations of a membrane oestrogen receptor. J Neuroendocrinol 25: 1219-30
Srivastava DP, Woolfrey KM, Jones KA, Anderson CT, Smith KR, Russell TA, Lee H, Yasvoina MV, Wokosin DL, Ozdinler PH, Shepherd GM, Penzes P (2012) An autism-associated variant of Epac2 reveals a role for Ras/Epac2 signaling in controlling basal dendrite maintenance in mice. PLoS Biol 10: e1001350
Woolfrey KM, Srivastava DP, Photowala H, Yamashita M, Barbolina MV, Cahill ME, Xie Z, Jones KA, Quilliam LA, Prakriya M, Penzes P (2009) Epac2 induces synapse remodeling and depression and its disease-associated forms alter spines. Nat Neurosci 12: 1275-84
Srivastava DP, Woolfrey KM, Woolfrey K, Jones KA, Shum CY, Lash LL, Swanson GT, Penzes P (2008) Rapid enhancement of two-step wiring plasticity by estrogen and NMDA receptor activity. Proc Natl Acad Sci U S A 105: 14650-5
Xie Z, Srivastava DP, Photowala H, Kai L, Cahill ME, Woolfrey KM, Shum CY, Surmeier DJ, Penzes P (2007) Kalirin-7 controls activity-dependent structural and functional plasticity of dendritic spines. Neuron 56: 640-56