
Adam E. Cohen
· Professor of Chemistry and Chemical Biology and PhysicsVerifiedHarvard University · Neuroscience
Active 1969–2026
About
Adam E. Cohen is a Professor of Chemistry and Chemical Biology and Physics at Harvard University, affiliated with the Departments of Chemistry and Chemical Biology and of Physics. His research focuses on understanding brain function through the development of advanced imaging tools and techniques. He has developed methods for high-resolution genetically targeted voltage imaging of neural populations in awake, behaving animals, and combines this with targeted optogenetic perturbations to investigate how neural circuits transform inputs to outputs. His current research includes studying the control of attention in cortical Layer 1 and mechanisms of plasticity in the hippocampus. Cohen's lab also works on creating new tools for probing the brain, such as techniques to increase the number of neurons that can be recorded simultaneously, all-optical tools for neural circuit mapping in vivo, and mapping the spatial structures of memories. His lab members come from diverse backgrounds including neuroscience, physics, chemistry, and molecular and cellular biology.
Research signals
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Research topics
- Neuroscience
- Biology
- Physics
- Psychology
Selected publications
bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-21
articleOpen accessSenior authorCorrespondingAbstract Dendrites transform local electrical activity into intracellular Ca 2+ signals that drive plasticity 1,2 , yet the voltage→Ca 2+ mapping during natural behavior remains poorly defined. Here, we measure this transfer function via simultaneous voltage and Ca 2+ imaging throughout the dendritic arbors of hippocampal CA2 pyramidal neurons in behaving mice. Dendritic Ca 2+ exhibited a hierarchical activation pattern dominated by back-propagating action potentials: simple spikes primarily drove somatic and proximal Ca 2+ , whereas complex spikes produced larger somatic Ca 2+ signals and propagated farther into distal dendrites, sometimes in a branch-selective manner. Dendrite-restricted co-activation of voltage and Ca 2+ without concurrent somatic events was rare. A biophysics-inspired model accurately predicted local Ca 2+ transients from local voltage waveforms. Our data and model provide a quantitative understanding of when – and why – dendritic Ca 2+ signals in CA2 pyramidal cells arise during behavior.
bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-03 · 2 citations
articleOpen accessSenior authorCorrespondingAbstract Dendrites integrate synaptic inputs to trigger action potentials, and dendrites carry back-propagating action potentials (bAPs) to synapses where these signals contribute to plasticity. Despite strong evidence for a rich repertoire of nonlinear dendritic excitations, the in vivo roles of these excitations in dendritic integration and back-propagation remain uncertain. Here, we used high-speed voltage imaging through a chronically implanted microprism to map membrane potential dynamics from basal to apical dendrites of CA1 neurons in mice navigating in a virtual reality environment. Despite complex dendritic branch morphology, the dynamics were largely captured by 2 or 3 electrical compartments: basal, soma, and apical. Fast dendritic spikes almost always started from bAPs, indicating that dendritic spikes are primarily a consequence rather than a cause of somatic spiking. These fast spikes sometimes triggered slower apical dendritic plateau depolarizations, which drove complex spikes at the soma. We found that the biophysics of dendritic excitability determined the distribution of simple and complex spikes across a place field. Our results show how CA1 pyramidal neurons convert synaptic inputs to spiking outputs and suggest a primary role of dendritic nonlinearities in mediating activity-dependent plasticity.
DMD-patterned structured illumination for imaging brain activity
2026-03-05
article1st authorCorrespondingMechanism of giant magnetic field effect in a red fluorescent protein
2026-03-04
article1st authorCorrespondingWe found that mScarlet3 fluorescence in E. coli reversibly decreased by 21% in the presence of a 60 mT magnetic field, the largest magnetic field effect (MFE) reported in any fluorescent protein. We developed a quantitative model of the giant MFE in mScarlet3. Our quantitative model of the photocycle provides a framework for the design and optimization of magnetic-field-sensitive proteins, opening possibilities in fluorescent protein-based magnetometry, magnetic imaging, and magnetogenetic control.
Ether lipids influence cancer cell fate by modulating iron uptake
Nature Communications · 2026-01-27 · 1 citations
articleOpen accessCancer cell fate has been widely ascribed to mutational changes within protein-coding genes associated with tumor suppressors and oncogenes. In contrast, the mechanisms through which the biophysical properties of membrane lipids influence cancer cell survival, dedifferentiation and metastasis have received little scrutiny. Here, we report that cancer cells endowed with high metastatic ability and cancer stem cell-like traits employ ether lipids to maintain low membrane tension and high membrane fluidity. Using genetic approaches and lipid reconstitution assays, we show that these ether lipid-regulated biophysical properties permit non-clathrin-mediated iron endocytosis via CD44, resulting in significant increases in intracellular redox-active iron and enhanced ferroptosis susceptibility. Using a combination of in vitro three-dimensional microvascular network systems and in vivo animal models, we show that loss of ether lipids from plasma membranes also strongly attenuates extravasation, metastatic burden and cancer stemness. These findings illuminate a mechanism whereby ether lipids in carcinoma cells serve as key regulators of malignant progression while conferring a unique vulnerability that can be exploited for therapeutic intervention. The contribution of ether lipid species in cancer cell fate has not been fully understood yet. Here the authors show that malignant cancer cells employ ether lipids to modulate membrane biophysical properties, enhancing iron endocytosis and ferroptosis susceptibility.
Nature Neuroscience · 2025-03-31 · 7 citations
articleSenior authorCorrespondingMechanism of Giant Magnetic Field Effect in a Red Fluorescent Protein
Journal of the American Chemical Society · 2025-05-15 · 8 citations
articleSenior authorCorrespondingSeveral fluorescent proteins, when expressed in E. coli, are sensitive to weak magnetic fields. We found that mScarlet3 fluorescence in E. coli reversibly decreased by 21% in the presence of a 60 mT magnetic field, the largest magnetic field effect (MFE) reported in any fluorescent protein. Purified mScarlet3 did not show an MFE, but the addition of flavin mononucleotide (FMN) and simultaneous illumination with blue and yellow light restored the MFE. Through extensive photophysical experiments, we developed a quantitative model of the giant MFE in mScarlet3-FMN mixtures. The key reaction step involved electron transfer from fully reduced FMNH2 to triplet-state mScarlet3 to form a triplet spin-correlated radical pair. The magnetic field then controlled the branching ratio between singlet recombination vs triplet separation. Our quantitative model of the mScarlet3-FMN photocycle provides a framework for the design and optimization of magnetic-field-sensitive proteins, opening possibilities in fluorescent protein-based magnetometry, magnetic imaging, and magnetogenetic control.
Current Biology · 2025-11-13 · 3 citations
articleOpen accessSenior authorElectrophysiology in nanoscale compartments
bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-04
preprintOpen accessSenior authorCorrespondingABSTRACT Voltage-gated ion channels play important roles in many membrane-enclosed structures, including synaptic vesicles, endosomes, mitochondria, chloroplasts, viruses and bacteria. Here we study how compartment size and channel gating interact to shape voltage dynamics and ion content in sub-micron structures. In small compartments, assumptions underlying conductance-based (Hodgkin-Huxley type) models of membrane voltage must be relaxed: [1] stochastic gating of individual ion channels can quickly and substantially change membrane voltage; [2] these changes can equilibrate faster than channel state transitions; and [3] ionic currents, even through as few as two channels, can substantially alter ionic concentrations. We adapted conductance-based models to incorporate these effects, and we then simulated voltage dynamics of small vesicles as a function of vesicle radius and channel density. We identified regimes in this parameter space with qualitatively distinct dynamics. We then performed stochastic simulations to explore the role of Na V 1.5 in maturation of macrophage endosomes. The stochastic model predicted dramatically different dynamics compared to a deterministic approach. Electrophysiology of nanoscale structures can be very different from larger structures, even when ion channel composition and density are preserved. SIGNIFICANCE With tools of optical electrophysiology, one can measure and perturb membrane voltage in sub-micron structures. Recent experiments in organelles, dendritic spines, and bacteria motivate a re-examination of basic assumptions about bioelectrical phenomena in these compartments. This paper provides a framework for predicting and interpreting bioelectrical dynamics in small structures.
Distribution of Eigenvalues of the Kohn Laplacian on Sphere Quotients
ArXiv.org · 2025-09-14
preprintOpen access1st authorCorrespondingWe prove a Weyl-type theorem for the Kohn Laplacian on sphere quotients as CR manifolds. We show that we can determine the fundamental group from the spectrum of the Kohn Laplacian in dimension three. Furthermore, we prove Sobolev estimates for the complex Green's operator on these quotient manifolds.
Recent grants
NIH · $2.5M · 2015
Trapping single small molecules in solution
NSF · $552k · 2009–2013
Engineering Microbial Rhodopsins as Optical Voltage Sensors
NIH · $371k · 2010–2014
Brain-wide correlation of single-cell firing properties to patterns of gene expression
NIH · $1.2M · 2018–2021
Engineering Microbial Rhodopsins as Optical Voltage Sensors
NIH · $1.1M · 2010–2014
Frequent coauthors
- 35 shared
Vicente Parot
Pontificia Universidad Católica de Chile
- 34 shared
Christopher A. Werley
- 32 shared
Yoav Adam
Hebrew University of Jerusalem
- 30 shared
Daan Brinks
Delft University of Technology
- 29 shared
Peng Zou
China Tobacco
- 28 shared
Dean A. Hendrickson
West Virginia University
- 25 shared
Miao‐Ping Chien
Erasmus MC
- 25 shared
Joel M. Kralj
University of Colorado Boulder
Labs
Education
- 2008
Ph.D., Neuroscience
Harvard University
- 2002
B.A., Psychology
University of California, Berkeley
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