The nervous system transmits information by passing chemical signals from one nerve cell to the others. This signal transmission relies on a variety of proteins to receive and transmit the chemical signals. My group studies the structure and function of neurotransmitter receptors and ion channels that regulate fundamental neuronal activities.
Hiro Furukawa’s lab studies receptor molecules involved in neurotransmission. Its members mainly focus on the structure and function of NMDA (N-methyl-d-aspartate) receptors — ion channels that mediate excitatory transmission. Dysfunctional NMDA receptors cause neurological disorders and diseases including Alzheimer’s disease, Parkinson’s disease, schizophrenia, depression, and stroke-related ischemic injuries. The Furukawa lab is working to solve the threedimensional structure of the very large NMDA receptor by dividing it into several domains. They seek to understand the pharmacological specificity of neurotransmitter ligands and allosteric modulators in different subtypes of NMDA receptors at the molecular level. Toward this end, they use cutting-edge techniques in X-ray crystallography to obtain crystal structures of the NMDA receptor domains and validate structure-based functional hypotheses by a combination of biophysical techniques including electrophysiology, fluorescence analysis, isothermal titration calorimetry, and analytical centrifugation. Crystal structures of NMDA receptors serve as a blueprint for creating and improving the design of therapeutic compounds with minimal side effects for treating neurological disorders and diseases. During the last several years, the team discovered and mapped several regulatory sites in specific classes of NMDA receptors, progress that now opens the way to the development of a new potential class of drugs to modulate the receptor activity.
Romero-Hernandez, Annabel and Simorowski, Noriko and Karakas, Erkan and Furukawa, Hiro (2016) Molecular Basis for Subtype Specificity and High-Affinity Zinc Inhibition in the GluN1-GluN2A NMDA Receptor Amino-Terminal Domain. Neuron, 92(6) pp. 1324-1336.
Tajima, N. and Karakas, E. and Grant, T. and Simorowski, N. and Diaz-Avalos, R. and Grigorieff, N. and Furukawa, H. (2016) Activation of NMDA receptors and the mechanism of inhibition by ifenprodil. Nature, 534(7605) pp. 63-8.
Karakas, E. and Furukawa, H. (2014) Crystal structure of a heterotetrameric NMDA receptor ion channel. Science, 344(6187) pp. 992-7.
Jespersen, A. and Tajima, N. and Fernandez-Cuervo, G. and Garnier-Amblard, E. C. and Furukawa, H. (2014) Structural Insights into Competitive Antagonism in NMDA Receptors. Neuron, 81(2) pp. 366-78.
Karakas, E. and Simorowski, N. and Furukawa, H. (2011) Subunit arrangement and phenylethanolamine binding in GluN1/GluN2B NMDA receptors. Nature, 475(7355) pp. 249- U170.Additional materials of the author at
CSHL Institutional Repository