Ph.D., The University of Tokyo, 2001
Membrane proteins, X-ray crystallography, electrophysiology, neurodegenerative disease
Communication between cells in both unicellular prokaryotes and multicellular animals involves the release, detection, and uptake of small molecules and ions, which are integral to complex patterns of growth and development in the cell. Signal transduction is a process by which cells register external stimuli and respond by changes to cellular pathways, including those involved in growth, differentiation, survival, movement, metabolism, homeostasis, fertilization, apoptosis, and brain physiology. Secreted or membrane-bound small molecules and ions, together with surface proteins or membrane proteins play fundamental roles in these signaling cascades. My lab is interested in gaining an understanding of the molecular basis for cellular signal transduction pathways that are triggered and regulated by cell surface receptors, ion channels, transporters, and intramembrane enzymes. In particular, our research is aimed at elucidating molecular mechanisms involved in signal transduction pathways in the brain that mediate functions such as learning and memory formation. Towards this end, we are conducting structural and functional studies of neurotransmitter receptors, ion channels, transporters, and intramembrane enzymes, which mediate and regulate the strength of synaptic transmission.
To achieve our goals, we use x-ray crystallography to obtain three-dimensional structures of target proteins and examine structure-based functional hypotheses by a combination of biochemistry and electrophysiology. Recently, new technologies have facilitated structural studies of membrane proteins. We are using the cutting-edge methods, and are also developing new methods for eukaryotic membrane protein crystallography. Since dysfunction of our target membrane proteins is associated with neurological disorders and diseases including seizure, stroke, Parkinson’s disease and Alzheimer’s disease, the structural and functional information that we obtain in these studies will likely pave novel ways for drug discovery.
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Karakas E, Simorowski N, Furukawa H. 2011. Subunit arrangement and phenylethanolamine binding in GluN1/GluN2B NMDA receptors. Nature. 475: 249-253.Vance KM, Simorowski N, Traynelis SF, and Furukawa H. 2011. Ligand-specific deactivation time course of GluN1/GluN2D NMDA receptors. Nat. Commun. 2:294 doi: 10.1038/ncomms1295.
Karakas, E., Simorowski, N., and Furukawa H. 2009. Structure of the zinc-bound amino-terminal domain of the NMDA receptor NR2B subunit. EMBO J. 28: 3910–3920.
Jasti, J., Furukawa, H., Gonzales, E.,and Gouaux, E. 2007. Structure of acid-sensing ion channel 1 at 1.9 Å resolution and low pH. Nature 449: 316-323.
Furukawa, H., Singh, S.K., Mancusso, R., and Gouaux, E. 2005. Subunit arrangement and function in NMDA receptors. Nature 438: 185–192.