Ph.D., University of Cambridge, England
Associate Professor
Department of Molecular Pharmacology, Physiology and Biotechnology
487 Biomedical Center
Tel: (401) 863-2574
Email: John_Marshall@Brown.edu
Go to lab web page

In response to hormonal or synaptic stimulation, excitable cells (including smooth muscle, cardiac muscle, and neurons) undergo a diversity of changes in their electrical properties. Changes in channel activity are known to regulate neuronal gene expression, cell death and communication. My lab is studying the regulation of glutamate receptors and potassium channels by protein kinases. Glutamate receptors play key roles in certain forms of synaptic plasticity and the failure to regulate these receptors can cause seizure disorders and neurodegenerative disease. We use patch-clamp techniques to study the electrophysiological properties of cloned glutamate receptors heterologously expressed in mammalian cell lines and Xenopus oocytes to determine how these properties are modulated by kinases such as protein kinase A, CaM-Kinase II and protein-tyrosine kinases (PTK). The PTK receptors, such as EGF, PDGF and the neurotrophin receptors are expressed on fully differentiated neurons and may also play an important role in regulating neuronal excitability. In addition to the glutamate receptor studies we have recently cloned a novel calcium-activated potassium channel. Site-directed mutagenesis methods are being used to determine its structure and how the gating properties of this channel are regulated by nitric oxide and other second messengers. Another focus of the lab is the development of optical methods that utilize the cloned jellyfish green fluorescent protein (GFP). We have engineered a chimeric NMDA/ GFP receptor subunit that can be observed by fluorescence microscopy while retaining its normal electrical properties. The tagging of receptors with GFP will enable us to visualize the expression and localization of ion channels in living cells.

Mehta S., Wu H., Garner CC, and Marshall J (2001) Intramolecular interactions regulate SAP97 binding to kainate receptors. J. Biol. Chem. 2001 276: 16092-16099.

Liu, Y-F., Sudol, M., Marshall, J (2000) Assignment of molecular mechanisms of neuronal death underlying Huntington's disease. J. Biol. Chem. 275, 19035-19040.

Blair, L.A.C., K.K. Bence and J. Marshall. (2000) Potentiation of neuronal L calcium channels by IGF-1 requires phosphorylation of the a1 subunit on a specific tyrosine residue. Neuron 27, 121-131.

Blair, L.A.C., K.K. Bence, T. Franke, D. Kaplan and J. Marshall. (1999) Akt-dependent potentiation of L channels by IGF-1 is required for neuronal survival. J. Neuroscience 19, 1940-51.

Garcia, E.P., Mehta, S., Blair, L.A.C., Wells, D.G., Shang, J., Fukushima. T., Fallon, J.R., Garner, C.C., and Marshall, J. (1998) SAP90 binds and clusters kainate receptors causing incomplete desensitization. Neuron 21, 727-39.