Jonathan Cohen

Jonathan Cohen, PhD

Bullard Professor of Neurobiology, Emeritus

Ion Channel and Neurotransmitter Biology

Neurons communicate with each other through the release of neurotransmitter molecules such as glutamate, GABA, acetylcholine, dopamine, serotonin, etc. at synapses. When a neurotransmitter binds to its receptor on the membrane of a neuron, it opens up ion channels that result in neuronal excitation or inhibition. Better understanding how this process works has many implications, both for basic neuroscience and our understanding of nervous system disorders.

The Cohen lab focuses on molecular studies of receptors for GABA, the major inhibitory neurotransmitter in the brain, and acetylcholine, an excitatory neurotransmitter in many brain regions and at nerve-muscle contacts. GABAA receptors (GABAAR) are the targets for many important drugs, including antiepileptics, sedatives and general anesthetics. One current project in the lab is focused on determining the diversity of general anesthetic biding sites in GABAARs, which will provide a basis for the development of anesthetics with fewer undesirable side effects.

Nicotinic acetylcholine receptors (nAChR), which are the site of binding of nicotine, are involved in the regulation of sleep, attention, learning, and memory. Dysfunctions of nAChRs are implicated in disorders including Alzheimer’s and Parkinson’s, and drugs that target nAChRs have potential uses in the treatment of these conditions as well as nicotine addiction. nAChRs on skeletal muscle mediate neural control of muscle contraction, and they are the receptors that are destroyed in an autoimmune disease, myasthenia gravis.  Currently the Cohen lab is studying the mechanisms of novel classes of drugs that act as enhancers of brain or muscle nAChRs.

Publications View
Competitive Antagonism of Etomidate Action by Diazepam.
Authors: Authors: McGrath M, Hoyt H, Pence A, Jayakar SS, Zhou X, Forman SA, Cohen JB, Miller KW, Raines DE.
Anesthesiology
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Photoaffinity labeling identifies an intersubunit steroid-binding site in heteromeric GABA type A (GABAA) receptors.
Authors: Authors: Jayakar SS, Chiara DC, Zhou X, Wu B, Bruzik KS, Miller KW, Cohen JB.
J Biol Chem
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Competitive Antagonism of Etomidate Action by Diazepam: In Vitro GABAA Receptor and In Vivo Zebrafish Studies.
Authors: Authors: McGrath M, Hoyt H, Pence A, Jayakar SS, Zhou X, Forman SA, Cohen JB, Miller KW, Raines DE.
Anesthesiology
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A potent photoreactive general anesthetic with novel binding site selectivity for GABAA receptors.
Authors: Authors: Shalabi AR, Yu Z, Zhou X, Jounaidi Y, Chen H, Dai J, Kent DE, Feng HJ, Forman SA, Cohen JB, Bruzik KS, Miller KW.
Eur J Med Chem
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Impact of Treatment Beyond Progression with Immune Checkpoint Blockade in Hodgkin Lymphoma.
Authors: Authors: Merryman RW, Carreau NA, Advani RH, Spinner MA, Herrera AF, Chen R, Tomassetti S, Ramchandren R, Hamid M, Assouline S, Santiago R, Nina Wagner-Johnston N, Paul S, Svoboda J, Bair SM, Barta SK, Liu Y, Nathan S, Karmali R, Burkart M, Torka P, David KA, Wei C, Lansigan F, Emery L, Persky D, Smith SM, Godfrey J, Chavez J, Cohen JB, Troxel AB, Diefenbach C, Armand P.
Oncologist
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Identifying Drugs that Bind Selectively to Intersubunit General Anesthetic Sites in the a1ß3?2 GABAAR Transmembrane Domain.
Authors: Authors: Jayakar SS, Zhou X, Chiara DC, Jarava-Barrera C, Savechenkov PY, Bruzik KS, Tortosa M, Miller KW, Cohen JB.
Mol Pharmacol
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A photoreactive analog of allopregnanolone enables identification of steroid-binding sites in a nicotinic acetylcholine receptor.
Authors: Authors: Yu Z, Chiara DC, Savechenkov PY, Bruzik KS, Cohen JB.
J Biol Chem
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Inhibitable photolabeling by neurosteroid diazirine analog in the ß3-Subunit of human hetereopentameric type A GABA receptors.
Authors: Authors: Wu B, Jayakar SS, Zhou X, Titterton K, Chiara DC, Szabo AL, Savechenkov PY, Kent DE, Cohen JB, Forman SA, Miller KW, Bruzik KS.
Eur J Med Chem
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Etomidate and Etomidate Analog Binding and Positive Modulation of ?-Aminobutyric Acid Type A Receptors: Evidence for a State-dependent Cutoff Effect.
Authors: Authors: McGrath M, Yu Z, Jayakar SS, Ma C, Tolia M, Zhou X, Miller KW, Cohen JB, Raines DE.
Anesthesiology
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Competitive Antagonism of Anesthetic Action at the ?-Aminobutyric Acid Type A Receptor by a Novel Etomidate Analog with Low Intrinsic Efficacy.
Authors: Authors: Ma C, Pejo E, McGrath M, Jayakar SS, Zhou X, Miller KW, Cohen JB, Raines DE.
Anesthesiology
View full abstract on Pubmed