John Gray, M.D., Ph.D.

 John  Gray, M.D., Ph.D.

Position

  • Assistant Professor
  • Neurology

NMDA Receptors and Synapse Regulation

Research Summary

Our laboratory focuses on understanding the molecular and cellular mechanisms involved in synapse development and plasticity throughout the brain. In particular, we study the regulation of the NMDA-type glutamate receptors that play crucial roles in synapse development and synaptic plasticity. Because of these important functions, dysregulation of NMDA receptors has been implicated in a broad range of neuropsychiatric disorders, including schizophrenia, autism, addiction, Alzheimer’s disease, Huntington’s disease and ischemia. By combining innovative genetic approaches with electrophysiology, imaging, and biochemistry to gain a detailed understanding of the molecular mechanisms involved in the regulation of NMDA receptors and synapses, we are striving to open new frontiers for the development of disease-modifying therapeutic approaches for complex neuropsychiatric disorders.

Select Publications

Peer-reviewed publications

Gray JA, Zito K, and Hell JW (2016). Non-ionotropic signaling by the NMDA receptor: controversy and opportunity. F1000 Research, 5(F1000 Faculty Rev): 1010.

Stein IS, Gray JA, and Zito K (2015). Non-ionotropic NMDA receptor signaling drives activity-induced dendritic spine shrinkage. Journal of Neuroscience, 35(35): 12303-12308.

Sanz-Clemente A, Gray JA, Nicoll RA, and Roche KW (2013). Activated CaMKII couples GluN2B and Casein Kinase 2 to control synaptic NMDA receptors. Cell Reports, 3(3): 607-614.

Gray JA and Nicoll RA (2012). Thinking outside the synapse: glycine at extrasynaptic NMDA receptors. Cell, 150(3): 455-456.

Chen BS*, Gray JA*, Sanz-Clemente A, Wei Z, Thomas EV, Nicoll RA, and Roche KW (2012). SAP102 mediates synaptic clearance of NMDA receptors. Cell Reports, 2(5): 1120-1128. (*co-first authors)

Gray JA (2012). Parkinsonism and rabbit syndrome following discontinuation of low-dose ziprasidone and concomitant initiation of sertraline. Journal of Clinical Psychopharmacology, 32(1): 142-143.

Gray JA, Shi Y, Usui H, During MJ, Sakimura K, Nicoll RA (2011). Distinct modes of AMPA receptor suppression at developing synapses by GluN2A and GluN2B: single-cell NMDA receptor subunit deletion in vivoNeuron, 71(6): 1085-1101.

Granger AJ, Gray JA, Lu W, and Nicoll RA (2011). Genetic analysis of neuronal ionotropic glutamate receptor subunits. Journal of Physiology,589(17): 4095-4101.

Lu W*, Gray JA*, Granger AJ, During MJ, Nicoll RA (2011). The potentiation of synaptic AMPA receptors induced by the deletion of NMDA receptors requires the GluA2 subunit. Journal of Neurophysiology, 105(2): 923-928. (*co-first authors)

Juge N, Gray JA, Omote H, Miyaji T, Inoue T, Hara C, Uneyama H, Edwards RH, Nicoll RA, Moriyama Y (2010). Metabolic control of vesicular glutamate transport and release. Neuron, 68(1): 99-112.

Gray JA and Risch SC (2009). When clozapine is not enough. Augment with lamotrigine? Current Psychiatry, 8(1): 41-46.

Berger M, Gray JA, and Roth BL (2009). The expanded biology of serotonin. Annual Review of Medicine, 60: 355-366.

Gray JA and Roth BL (2007). The pipeline and future of drug development in schizophrenia. Molecular Psychiatry, 12(10): 904-922.

Gray JA and Roth BL (2007). Molecular targets for treating cognitive dysfunction in schizophrenia. Schizophrenia Bulletin, 33(5): 1100-1119.

Gray JA and Roth BL (2006). Developing selectively non-selective drugs for treating CNS disorders. Drug Discovery Today: Therapeutic Strategies, 3(4): 413-419.

Xia Z, Hufeisen SJ, Gray JA, and Roth BL (2003). The PDZ-binding domain is essential for the dendritic targeting of 5-HT2A serotonin receptors in cortical pyramidal neurons in vitroNeuroscience, 122(4): 907-920.

Gray JA, Compton-Toth BA, and Roth BL (2003). Identification of two serine residues essential for agonist-induced 5-HT2A receptor desensitization. Biochemistry, 42(36): 10853-10862.

Xia Z, Gray JA, Compton-Toth BA, and Roth BL (2003). A direct interaction of PSD-95 with 5-HT2A serotonin receptors regulates receptor trafficking and signal transduction. Journal of Biological Chemistry 278(24): 21901-21908.

Gray JA, Bhatnagar A, Gurevich VV, and Roth BL (2003). The interaction of a constitutively active arrestin with the arrestin-insensitive 5-HT2A receptor induces agonist-independent internalization. Molecular Pharmacology 63(5): 961-972.

Gray JA and Roth BL (2002). A Last GASP for GPCRs? Science 297: 529-531.

Gray JA, Sheffler DJ, Bhatnagar A, Woods JA, Hufeisen SJ, Benovic JL, and Roth BL (2001). Cell-type specific effects of endocytosis inhibitors on 5-HT2A receptor desensitization and resensitization reveal an arrestin-, GRK2- and GRK5-independent mode of regulation in HEK-293 cells. Molecular Pharmacology 60(5): 1020-1030.

Gray JA and Roth BL (2001). Paradoxical trafficking and regulation of 5-HT2A receptors by agonists and antagonists. Brain Research Bulletin56(5): 441-451.

Bhatnagar A, Willins DL, Gray JA, Woods JA, Benovic JL, and Roth BL (2001). The dynamin-dependent, arrestin-independent internalization of 5-hydroxytryptamine2A (5-HT2A) serotonin receptors reveals differential sorting of arrestins and 5-HT2A receptors during endocytosis.Journal of Biological Chemistry 276(11): 8269-8277.

Gelber EI, Kroeze WK, Willins DL, Gray JA, Sinar CA, Hyde EG, Gurevich V, Benovic JL, and Roth BL (1999). Structure and function of the third intracellular loop of the 5-hydroxytryptamine2A receptor: the third intracellular loop is alpha-helical and binds purified arrestins. Journal of Neurochemistry 72: 2206-2214.

Book Chapters

Gray JA (2016). Introduction to the Pharmacology of CNS Drugs, in Basic and Clinical Pharmacology. Katzung BG (Ed.), McGraw-Hill, New York, NY, in press.

Gray JA (2016). Tardive Dyskinesia, in Ferri’s Clinical Advisor 2017. Ferri FF (Ed.), Mosbi, Philadelphia, PA, in press.

Gray JA (2015). Tardive Dyskinesia, in Ferri’s Clinical Advisor 2016. Ferri FF (Ed.), Mosbi, Philadelphia, PA, p 1198.

Gray JA and Nicoll RA (2014). Introduction to the Pharmacology of CNS Drugs, in Basic and Clinical Pharmacology. Katzung BG (Ed.), McGraw-Hill, New York, NY, pp 355-368.

Gray JA (2014). Tardive Dyskinesia, in Ferri’s Clinical Advisor 2015. Ferri FF (Ed.), Mosbi, Philadelphia, PA, p 1148.

Gray JA (2013). Tardive Dyskinesia, in Ferri’s Clinical Advisor 2014. Ferri FF (Ed.), Mosbi, Philadelphia, PA, p 1078.

Gray JA (2012). Tardive Dyskinesia, in Ferri’s Clinical Advisor 2013. Ferri FF (Ed.), Mosbi, Philadelphia, PA, p 1067.

Gray JA (2011). Tardive Dyskinesia, in Ferri’s Clinical Advisor 2012. Ferri FF (Ed.), Mosbi, Philadelphia, PA, p 997.

Gray JA (2010). Tardive Dyskinesia, in Ferri’s Clinical Advisor 2011. Ferri FF (Ed.), Mosbi, Philadelphia, PA, pp 1069-1070.

Gray JA and Roth BL (2009). Intraneuronal Signaling, in Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. Sadock BJ, Sadock VA and Ruiz P (Eds.) Lippincott Williams & Wilkins, Philadelphia, PA, pp 118-129.

Gray JA and Lai A (2009). Tardive Dyskinesia, in Ferri’s Clinical Advisor 2010. Ferri FF (Ed.), Mosbi, Philadelphia, PA, p 976.

Gray JA and Roth BL (2007). Serotonin Systems, in Handbook of Contemporary Neuropharmacology. Sibley DR, Hanin I, Kuhar M and Skolnick P (Eds.), John Wiley & Sons, New York, NY, pp 257-298.

Affiliations

Center for Neuroscience

Department of Neurology

Neuroscience Graduate Group

Pharmacology and Toxicology (PTX) Graduate Group

Biochemistry, Molecular, Cellular, and Developmental Biology (BMCDB) Graduate Group