Chunyang Dong completed his Ph.D. studies from University of California, Davis with Dr. Lin Tian, where he specialized in protein engineering to develop genetically encoded biosensors to enable real-time imaging of neuromodulator dynamics. As part of his postdoctoral pursuits with Dr. Sergiu Pasca at Stanford University, he hopes to combine disciplines between biosensors and modeling human neurological disease using brain region-specific organoids. Despite this shift, his unwavering goal is to deepen the understanding of brain development, disease processes, and translate research to potential treatments for neurological disorders.
Honors & Awards
Allen G. Marr Dissertation Award, University of California Davis (2023)
Toni Shippenberg Young Investigator Award, KappaCon (2023)
Sergiu Pasca, Postdoctoral Faculty Sponsor
Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors
2023; 379 (6633): 700-706
Decreased dendritic spine density in the cortex is a hallmark of several neuropsychiatric diseases, and the ability to promote cortical neuron growth has been hypothesized to underlie the rapid and sustained therapeutic effects of psychedelics. Activation of 5-hydroxytryptamine (serotonin) 2A receptors (5-HT2ARs) is essential for psychedelic-induced cortical plasticity, but it is currently unclear why some 5-HT2AR agonists promote neuroplasticity, whereas others do not. We used molecular and genetic tools to demonstrate that intracellular 5-HT2ARs mediate the plasticity-promoting properties of psychedelics; these results explain why serotonin does not engage similar plasticity mechanisms. This work emphasizes the role of location bias in 5-HT2AR signaling, identifies intracellular 5-HT2ARs as a therapeutic target, and raises the intriguing possibility that serotonin might not be the endogenous ligand for intracellular 5-HT2ARs in the cortex.
View details for DOI 10.1126/science.adf0435
View details for Web of Science ID 000994361400002
View details for PubMedID 36795823
View details for PubMedCentralID PMC10108900
Fluorescence Imaging of Neural Activity, Neurochemical Dynamics, and Drug-Specific Receptor Conformation with Genetically Encoded Sensors
ANNUAL REVIEW OF NEUROSCIENCE
2022; 45: 273-294
Recent advances in fluorescence imaging permit large-scale recording of neural activity and dynamics of neurochemical release with unprecedented resolution in behaving animals. Calcium imaging with highly optimized genetically encoded indicators provides a mesoscopic view of neural activity from genetically defined populations at cellular and subcellular resolutions. Rigorously improved voltage sensors and microscopy allow for robust spike imaging of populational neurons in various brain regions. In addition, recent protein engineering efforts in the past few years have led to the development of sensors for neurotransmitters and neuromodulators. Here, we discuss the development and applications of these genetically encoded fluorescent indicators in reporting neural activity in response to various behaviors in different biological systems as well as in drug discovery. We also report a simple model to guide sensor selection and optimization.
View details for DOI 10.1146/annurev-neuro-110520-031137
View details for Web of Science ID 000826690800013
View details for PubMedID 35316611
View details for PubMedCentralID PMC9940643
Psychedelic-inspired drug discovery using an engineered biosensor
2021; 184 (10): 2779-+
Ligands can induce G protein-coupled receptors (GPCRs) to adopt a myriad of conformations, many of which play critical roles in determining the activation of specific signaling cascades associated with distinct functional and behavioral consequences. For example, the 5-hydroxytryptamine 2A receptor (5-HT2AR) is the target of classic hallucinogens, atypical antipsychotics, and psychoplastogens. However, currently available methods are inadequate for directly assessing 5-HT2AR conformation both in vitro and in vivo. Here, we developed psychLight, a genetically encoded fluorescent sensor based on the 5-HT2AR structure. PsychLight detects behaviorally relevant serotonin release and correctly predicts the hallucinogenic behavioral effects of structurally similar 5-HT2AR ligands. We further used psychLight to identify a non-hallucinogenic psychedelic analog, which produced rapid-onset and long-lasting antidepressant-like effects after a single administration. The advent of psychLight will enable in vivo detection of serotonin dynamics, early identification of designer drugs of abuse, and the development of 5-HT2AR-dependent non-hallucinogenic therapeutics.
View details for DOI 10.1016/j.cell.2021.03.043
View details for Web of Science ID 000652830800019
View details for PubMedID 33915107
View details for PubMedCentralID PMC8122087
Directed Evolution of a Selective and Sensitive Serotonin Sensor via Machine Learning
2020; 183 (7): 1986-+
Serotonin plays a central role in cognition and is the target of most pharmaceuticals for psychiatric disorders. Existing drugs have limited efficacy; creation of improved versions will require better understanding of serotonergic circuitry, which has been hampered by our inability to monitor serotonin release and transport with high spatial and temporal resolution. We developed and applied a binding-pocket redesign strategy, guided by machine learning, to create a high-performance, soluble, fluorescent serotonin sensor (iSeroSnFR), enabling optical detection of millisecond-scale serotonin transients. We demonstrate that iSeroSnFR can be used to detect serotonin release in freely behaving mice during fear conditioning, social interaction, and sleep/wake transitions. We also developed a robust assay of serotonin transporter function and modulation by drugs. We expect that both machine-learning-guided binding-pocket redesign and iSeroSnFR will have broad utility for the development of other sensors and in vitro and in vivo serotonin detection, respectively.
View details for DOI 10.1016/j.cell.2020.11.040
View details for Web of Science ID 000602900800018
View details for PubMedID 33333022
View details for PubMedCentralID PMC8025677
An expanded palette of dopamine sensors for multiplex imaging in vivo
2020; 17 (11): 1147-+
Genetically encoded dopamine sensors based on green fluorescent protein (GFP) enable high-resolution imaging of dopamine dynamics in behaving animals. However, these GFP-based variants cannot be readily combined with commonly used optical sensors and actuators, due to spectral overlap. We therefore engineered red-shifted variants of dopamine sensors called RdLight1, based on mApple. RdLight1 can be combined with GFP-based sensors with minimal interference and shows high photostability, permitting prolonged continuous imaging. We demonstrate the utility of RdLight1 for receptor-specific pharmacological analysis in cell culture, simultaneous assessment of dopamine release and cell-type-specific neuronal activity and simultaneous subsecond monitoring of multiple neurotransmitters in freely behaving rats. Dual-color photometry revealed that dopamine release in the nucleus accumbens evoked by reward-predictive cues is accompanied by a rapid suppression of glutamate release. By enabling multiplexed imaging of dopamine with other circuit components in vivo, RdLight1 opens avenues for understanding many aspects of dopamine biology.
View details for DOI 10.1038/s41592-020-0936-3
View details for Web of Science ID 000566893800001
View details for PubMedID 32895537
View details for PubMedCentralID PMC8169200