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.
Picky proteins: A new angle for brain disorder therapeutics
May 20, 2022
Researchers have designed an antibody that may help treat brain disorders. See how it prevents neurons from malfunctioning.
CSHL Professor Hiro Furukawa wins Tsukahara Memorial Award
August 6, 2021
CSHL Professor Hiro Furukawa was awarded the Nakaakira Tsukahara Memorial Award from the Japan Neuroscience Society for his NMDA receptor research.
Cold Spring Harbor Laboratory’s class of 2020
August 7, 2020
Meet the seven graduates of the Cold Spring Harbor Laboratory School of Biological Sciences. Congratulations to all.
Brain receptor pulls open electrical gate like a puppet master
June 30, 2020
When stimulated by a neurotransmitter or drug, the NMDA receptor pulls open an ion gate that allows ions to flow.
How does the NMDA receptor work?
June 30, 2020
CSHL Professor Hiro Furukawa describes how the NMDA receptor opens and closes its ion channel.
Images of ‘invisible’ holes on cells may jumpstart research
March 3, 2020
Cellular pores, once impossible to see, have been imaged for the first time. This sets the stage for new discoveries about blood pressure and pain.
New look at odd holes involved in taste, Alzheimer’s, asthma
January 27, 2020
Large holes in our cells have been implicated in depression, Alzehimer’s disease, asthma, and even taste. Now, we know what two of these pores look like.
New tool for investigating brain cells, Parkinson’s, & more
January 22, 2020
Researchers have created a new chemical tool for revealing how specific types of brain cell receptors function in the brain.
New tool for investigating brain cells, Parkinson’s, & more
January 22, 2020
Researchers have crafted a compound for targeting specific brain cell receptors, creating new opportunities to study the brain and Parkinson’s disease.
Targeting ‘hidden pocket’ for treatment of stroke and seizure
January 18, 2019
Researchers have identified a hidden molecular “pocket” in a special neuron receptor, which could lead to better treatments for stroke and seizures.
Selected Publications
On the molecular nature of large-pore channels.
15 Apr 2021 | Journal of Molecular Biology | :166994
Syrjanen, Johanna, Michalski, Kevin, Kawate, Toshimitsu, Furukawa, Hiro
Hodgkin-Huxley-Katz Prize Lecture: Genetic and pharmacological control of glutamate receptor channel through a highly conserved gating motif
Aug 2020 | The Journal of Physiology | 598(15):3071-3083
Perszyk, R, Myers, S, Yuan, H, Gibb, A, Furukawa, H, Sobolevsky, A, Traynelis, S
Publisher Correction: Structure and assembly of calcium homeostasis modulator proteins.
Mar 2020 | Nature Structural and Molecular Biology | 27(3):305
Syrjanen, Johanna, Michalski, Kevin, Chou, Tsung-Han, Grant, Timothy, Rao, Shanlin, Simorowski, Noriko, Tucker, Stephen, Grigorieff, Nikolaus, Furukawa, Hiro
The cryo-EM structure of a pannexin 1 reveals unique motifs for ion selection and inhibition
12 Feb 2020 | eLife | 9
Michalski, K, Syrjanen, J, Henze, E, Kumpf, J, Furukawa, H, Kawate, T
All Publications
Development and characterization of functional antibodies targeting NMDA receptors
17 Feb 2022 | Nature Communications | 13(1):923
Tajima, Nami, Simorowski, Noriko, Yovanno, Remy, Regan, Michael, Michalski, Kevin, Gómez, Ricardo, Lau, Albert, Furukawa, Hiro
Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels
Oct 2021 | Pharmacological Reviews | 73(4):298-487
Hansen, Kasper, Wollmuth, Lonnie, Bowie, Derek, Furukawa, Hiro, Menniti, Frank, Sobolevsky, Alexander, Swanson, Geoffrey, Swanger, Sharon, Greger, Ingo, Nakagawa, Terunaga, McBain, Chris, Jayaraman, Vasanthi, Low, Chian-Ming, Dell'Acqua, Mark, Diamond, Jeffrey, Camp, Chad, Perszyk, Riley, Yuan, Hongjie, Traynelis, Stephen
Structural Mechanism for Modulation of Synaptic Neuroligin-Neurexin Signaling by MDGA Proteins.
6 Jan 2021 | Neuron | 109(1):189-190
Elegheert, Jonathan, Cvetkovska, Vedrana, Clayton, Amber, Heroven, Christina, Vennekens, Kristel, Smukowski, Samuel, Regan, Michael, Jia, Wanyi, Smith, Alexandra, Furukawa, Hiro, Savas, Jeffrey, de Wit, Joris, Begbie, Jo, Craig, Ann, Aricescu, A
Structural Basis of Functional Transitions in Mammalian NMDA Receptors.
23 Jul 2020 | Cell | 182(2):357-371.e13
Chou, Tsung-Han, Tajima, Nami, Romero-Hernandez, Annabel, Furukawa, Hiro
Structure and assembly of calcium homeostasis modulator proteins
27 Jan 2020 | Nature Structural and Molecular Biology | 27(2):150-159
Syrjanen, J, Michalski, K, Chou, T, Grant, T, Rao, S, Simorowski, N, Tucker, S, Grigorieff, N, Furukawa, H
Structural basis of subtype-selective competitive antagonism for GluN2C/2D-containing NMDA receptors
22 Jan 2020 | Nature Communications | 11(1):423
Wang, J, Irvine, M, Burnell, E, Sapkota, K, Thatcher, R, Li, M, Simorowski, N, Volianskis, A, Collingridge, G, Monaghan, D, Jane, D, Furukawa, H