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.
This eight-armed octopus-like pore perceives taste
July 14, 2023
CSHL captures never-before-seen images of the human CALHM1 channel, a mysterious cellular passageway that may be connected to Alzheimer’s disease.
A new look at brain function and psychiatric disorders
November 2, 2022
CSHL scientists’ new 3D models of NMDA brain receptor variants could lead to better treatments for schizophrenia, stroke, depression, and Alzheimer’s.
Mapping brain disorder therapeutics at work
July 29, 2022
Dive into the 3D atomic structure of the NMDA receptor, important in several brain disorders, and see how it interacts with drugs that inhibit it.
Mapping out new routes to treat brain disorders
June 10, 2022
CSHL scientists explore new angles to improve brain disorder therapies with 3D maps of the NMDA receptor, a key player in Alzheimer's and epilepsy.
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.
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
Dendritic, delayed, and stochastic CaMKII activation underlies behavioral time scale plasticity in CA1 synapses
01 Aug 2023 | bioRxiv
Jain, Anant, Nakahata, Yoshihisa, Watabe, Tetsuya, Rusina, Polina, South, Kelly, Adachi, Kengo, Yan, Long, Simorowski, Noriko, Furukawa, Hiro, Yasuda, Ryohei
Structure of human CALHM1 reveals key locations for channel regulation and blockade by ruthenium red.
28 Jun 2023 | Nature Communications | 14(1):3821
Syrjänen, Johanna, Epstein, Max, Gómez, Ricardo, Furukawa, Hiro
Novel GluN2B-Selective NMDA Receptor Negative Allosteric Modulator Possesses Intrinsic Analgesic Properties and Enhances Analgesia of Morphine in a Rodent Tail Flick Pain Model
13 Feb 2023 | ACS Chemical Neuroscience
Harris, Lynnea, Regan, Michael, Myers, Scott, Nocilla, Kelsey, Akins, Nicholas, Tahirovic, Yesim, Wilson, Lawrence, Dingledine, Ray, Furukawa, Hiro, Traynelis, Stephen, Liotta, Dennis
Excitatory and inhibitory D-serine binding to the NMDA receptor
27 Oct 2022 | eLife | 11:e77645
Yovanno, Remy, Chou, Tsung, Brantley, Sarah, Furukawa, Hiro, Lau, Albert
Structural insights into assembly and function of GluN1-2C, GluN1-2A-2C, and GluN1-2D NMDARs
20 Oct 2022 | Molecular Cell | :S1097-2765(22)00965
Chou, Tsung-Han, Kang, Hyunook, Simorowski, Noriko, Traynelis, Stephen, Furukawa, Hiro
GluN2A-selective NMDA receptor antagonists: Mimicking the U-shaped bioactive conformation of TCN-201 by a [2.2]paracyclophane system
28 Sep 2022 | ChemMedChem: chemistry enabling drug discovery
Steigerwald, Ruben, Chou, Tsung-Han, Furukawa, Hiro, Wünsch, Bernhard