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.
How key brain receptor works in hostile conditions
May 9, 2018
Cold Spring Harbor, NY — During a stroke or an epileptic seizure, neurons in affected parts of the brain fire at an abnormally rapid rate. One byproduct of this condition is that the pH of the brain drops markedly, rendering the local environment inhospitably acidic. Using a powerful microscopy method called cryo-EM, biologists at Cold...
Portrait of a Neuroscience Powerhouse
April 27, 2018
At noon every Tuesday from September through June, scenes from a revolution in neuroscience are playing out at Cold Spring Harbor Laboratory. Week after week, over 100 scientists cram themselves into a ground-floor meeting room in the Beckman Laboratory. It’s standing-room only as everyone in the Neuroscience Program settles in to hear details of the...
Can we understand memories at the molecular level?
March 13, 2017
LabDish blog Written by Annabel Romero Hernandez Memories may seem intangible, but many scientists are working to figure out how they are physically stored in the brain. To achieve this, we’ll need to understand memories at the molecular level. When we talk about memories, it’s usually in the context of something precious, like a beloved...
New art supplies for visualizing tiny machines in the brain
March 1, 2017
LabDish blog Written by Annabel Romero Hernandez An unusual, but beautiful sight can be found among the figures of a recent scientific paper about some of the tiny machines in our brain: watercolor paintings by Annabel Romero Hernandez, who just graduated from CSHL’s Watson School of Biological Sciences. Staring intently at a watercolor painting of...
Austin’s Purpose Raises $10,000 for Cold Spring Harbor Laboratory Neuroscience
January 4, 2017
Austin Wasielewski, born in May 2003, at first appeared to be a healthy, strong boy. About three months into his life his parents noticed his jerking motions and realized he wasn’t meeting developmental goals. On Thanksgiving Day 2003, Austin had his first myoclonic seizure. Throughout his first eight years of life he would have up...
Detailed images of NMDA receptor show how zinc and a potential drug affect its function
December 1, 2016
Drugs precisely targeting portions of this receptor may have applications in Alzheimer’s, depression and schizophrenia Cold Spring Harbor, NY — The difference between mental health and mental illness can turn on changes in brain cells and their connections that are almost incomprehensibly tiny, at least in physical terms. This irony is brought to light by...
First structural views of the NMDA receptor in action will aid drug development
May 2, 2016
Cold Spring Harbor, NY – Structural biologists at Cold Spring Harbor Laboratory (CSHL) and Janelia Research Campus/HHMI, have obtained snapshots of the activation of an important type of brain-cell receptor. Dysfunction of the receptor has been implicated in a range of neurological illnesses, including Alzheimer’s disease, Parkinson’s disease, depression, seizure, schizophrenia, autism, and injuries related...
Scientific inspiration with third-year student Annabel Romero Hernandez
September 1, 2015
Biology is a question of scale. Some biologists study the large scale—populations or whole organisms. Some biologists study a medium scale, organs and tissues or even single cells. Still others may look for understanding at a smaller scale, such as cellular compartments or molecular complexes. And the biochemists study the smallest scale: molecules, and the...
Unprecedented detail of intact neuronal receptor offers blueprint for drug developers
May 29, 2014
NMDA receptor malfunction is implicated in Alzheimer’s, Parkinson’s, depression, schizophrenia, autism, and stroke Cold Spring Harbor, NY — Biologists at Cold Spring Harbor Laboratory (CSHL) report today that they have succeeded in obtaining an unprecedented view of a type of brain-cell receptor that is implicated in a range of neurological illnesses, including Alzheimer’s disease, Parkinson’s...
Unprecedented structural insights reveal how NMDA receptors can be blocked, to limit neurotoxicity
January 22, 2014
Cold Spring Harbor, NY – Structural biologists at Cold Spring Harbor Laboratory (CSHL) and collaborators at Emory University have obtained important scientific results likely to advance efforts to develop new drugs targeting NMDA receptors in the brain. NMDA (N-methyl D-aspartate) receptors are found on the surface of many nerve cells and are involved in signaling...
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 atCSHL Institutional Repository