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Angela Kwan

· Physical TherapistVerified

Yale University · Doctor of Physical Therapy Program

Active 1980–2026

h-index28
Citations4.1k
Papers11374 last 5y
Funding
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About

Dr. Angela Kwan is an Assistant Professor of Clinical Physical Therapy at the USC Division of Biokinesiology and Physical Therapy. She has been involved in wound care for more than 15 years and currently serves as the lead in-patient wound care physical therapist at Keck Hospital at USC. Her clinical practice involves treating a wide range of patients with complex surgical, vasculitic, pressure, diabetic, and atypical wounds. Dr. Kwan is a Certified Wound Specialist (CWS) through the American Board of Wound Management since 2008 and has been a certified clinical instructor through APTA since 2005. Her educational background includes a Doctor of Physical Therapy degree from the College of St. Scholastica, a Master of Physical Therapy from the University of Maryland, and a Bachelor of Science in Biology from the University of California, Riverside.

Research topics

  • Neuroscience
  • Biology
  • Psychology
  • Biochemistry
  • Psychiatry
  • Medicine
  • Internal medicine
  • Chemistry

Selected publications

  • Psilocybin reshapes cortical inhibition through selective interneuron recruitment

    bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-17

    articleOpen accessSenior authorCorresponding

    Psychedelics show therapeutic potential for treating psychiatric disorders. While studies have emphasized the roles of cortical pyramidal cells, GABAergic neurons also express serotonin receptors and are therefore likely targets of psychedelics. In this study, we determine the effect of psilocybin on the activity dynamics of major GABAergic cell types in the mouse medial frontal cortex. Psilocybin reduces the firing of somatostatin-expressing interneurons, but increases the activity of parvalbumin-expressing interneurons. This cell type-specific response is unlikely to involve vasoactive intestinal peptide-expressing interneurons. Instead, pharmacological blockade and conditional knockout experiments demonstrate that psilocybin acts on the 5-HT1A receptor at SST interneurons, which contributes to the drug's long-term behavioral effects. Collectively, the results reveal that the classic psychedelic psilocybin alters cortical inhibition in a cell type-specific manner.

  • Dorsal Raphe Revisited: A Systems Neuroscience Lens on Psychedelic Drug Action

    Psychedelic Medicine · 2026-04-09

    article1st authorCorresponding

    Psychedelics rose to prominence in the 1960s, around the same time when neurobiologists identified the midbrain raphe as the brain’s primary source of serotonin. It is therefore no surprise that early studies on classical psychedelics like d -lysergic acid diethylamide (LSD) focused on their effects within this brainstem nucleus. This review traces the arc of discovery: from the initial report in 1968 that LSD suppresses the firing of serotonergic neurons in the rat midbrain raphe, through more than 15 years of intensive work dissecting the pharmacology and receptor mechanisms. Early hypotheses erroneously suggested the serotonergic neurons as potential drivers of the acute hallucinogenic effects, but the conceptual framework gradually shifted after relating neural activity to behavior. We conclude this brief commentary by revisiting these early findings in light of current knowledge of the serotonergic circuits. Collectively, the pioneering studies laid the foundation for thinking about how psychedelics act on the brain through the lens of neurophysiology.

  • Structural plasticity and enhanced fear extinction following psilocybin in chronically stressed mice

    bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-22

    articleOpen accessSenior authorCorresponding

    The classic psychedelic psilocybin elicits long-lasting neural plasticity and behavioral effects, but prior studies largely examined stress-naive animals. Using longitudinal imaging, we show that psilocybin increases dendritic spine density in frontal cortical neurons and facilitates fear extinction after chronic restraint stress, demonstrating psilocybin's effects in a translationally relevant mouse model.

  • Classification of psychedelics and psychoactive drugs based on brain-wide imaging of cellular c-Fos expression

    Nature Communications · 2025-02-12 · 19 citations

    articleOpen accessSenior authorCorresponding

    Psilocybin, ketamine, and MDMA are psychoactive compounds that exert behavioral effects with distinguishable but also overlapping features. The growing interest in using these compounds as therapeutics necessitates preclinical assays that can accurately screen psychedelics and related analogs. We posit that a promising approach may be to measure drug action on markers of neural plasticity in native brain tissues. We therefore developed a pipeline for drug classification using light sheet fluorescence microscopy of immediate early gene expression at cellular resolution followed by machine learning. We tested male and female mice with a panel of drugs, including psilocybin, ketamine, 5-MeO-DMT, 6-fluoro-DET, MDMA, acute fluoxetine, chronic fluoxetine, and vehicle. In one-versus-rest classification, the exact drug was identified with 67% accuracy, significantly above the chance level of 12.5%. In one-versus-one classifications, psilocybin was discriminated from 5-MeO-DMT, ketamine, MDMA, or acute fluoxetine with >95% accuracy. We used Shapley additive explanation to pinpoint the brain regions driving the machine learning predictions. Our results suggest a unique approach for characterizing and validating psychoactive drugs with psychedelic properties. A challenge in psychiatric drug discovery is to predict the therapeutic potential of a novel compound. Here, the authors show that brain-wide imaging of immediate early gene expression can be used to classify a panel of drugs including psychedelics and antidepressants with high accuracy.

  • Autism-associated <i>Scn2a</i> haploinsufficiency disrupts <i>in vivo</i> dendritic signaling and impairs flexible decision-making

    bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-09 · 2 citations

    preprintOpen accessSenior authorCorresponding

    ABSTRACT SCN2A is a high-confidence risk gene for autism spectrum disorder. Loss-of-function mutations in Scn2a reduce dendritic excitability in neocortical pyramidal cells. However, the impact of Scn2a haploinsufficiency on dendritic signaling in vivo , particularly during behavior, is unknown. In this study, we used two-photon microscopy to image dendritic calcium transients in deep layer pyramidal cells in the mouse medial frontal cortex. Scn2a +/- mice had diminished coupling between apical and proximal dendritic compartments. Pyramidal tract neurons had abnormal event rates, while intratelencephalic neurons had compartment-specific alterations indicative of diminished dendritic integration. In a matching pennies task, Scn2a +/- mice were inflexible in the face of changing competitive pressure. Apical dendritic tuft in IT neurons typically encoded reward and strategy, but these task-specific representations were altered in Scn2a +/- mice. Collectively, the findings demonstrate that Scn2a haploinsufficiency weakens dendritic integration in vivo and disrupts the dendritic encoding of decision variables, potentially contributing to the cognitive rigidity in autism spectrum disorder.

  • Psilocybin’s lasting action requires pyramidal cell types and 5-HT2A receptors

    Nature · 2025-04-02 · 65 citations

    articleSenior author
  • Psilocybin triggers an activity-dependent rewiring of large-scale cortical networks

    Cell · 2025-12-05 · 11 citations

    articleOpen accessSenior author

    Psilocybin holds promise as a treatment for mental illnesses. One dose of psilocybin induces structural remodeling of dendritic spines in the medial frontal cortex in mice. The dendritic spines would be innervated by presynaptic neurons, but the sources of these inputs have not been identified. Here, using monosynaptic rabies tracing, we map the brain-wide distribution of inputs to frontal cortical pyramidal neurons. We discover that psilocybin's effect on connectivity is network specific, strengthening the routing of inputs from perceptual and medial regions (homolog of the default mode network) to subcortical targets while weakening inputs that are part of cortico-cortical recurrent loops. The pattern of synaptic reorganization depends on the drug-evoked spiking activity because silencing a presynaptic region during psilocybin administration disrupts the rewiring. Collectively, the results reveal the impact of psilocybin on the connectivity of large-scale cortical networks and demonstrate neural activity modulation as an approach to sculpt the psychedelic-evoked neural plasticity.

  • Frontal noradrenergic and cholinergic transients exhibit distinct spatiotemporal dynamics during competitive decision-making

    Science Advances · 2025-03-26 · 3 citations

    articleOpen accessSenior authorCorresponding

    Norepinephrine (NE) and acetylcholine (ACh) are crucial for learning and decision-making. In the cortex, NE and ACh are released transiently at specific sites along neuromodulatory axons, but how the spatiotemporal patterns of NE and ACh signaling link to behavioral events is unknown. Here, we use two-photon microscopy to visualize neuromodulatory signals in the premotor cortex (medial M2) as mice engage in a competitive matching pennies game. Spatially, NE signals are more segregated with choice and outcome encoded at distinct locations, whereas ACh signals can multiplex and reflect different behavioral correlates at the same site. Temporally, task-driven NE transients were more synchronized and peaked earlier than ACh transients. To test functional relevance, we stimulated neuromodulatory signals using optogenetics to find that NE, but not ACh, increases the animals' propensity to explore alternate options. Together, the results reveal distinct subcellular spatiotemporal patterns of ACh and NE transients during decision-making in mice.

  • SIFa peptidergic neurons orchestrate the internal states and energy balance of male Drosophila melanogaster

    PLoS Biology · 2025-09-04 · 3 citations

    articleOpen accessCorresponding

    Neuropeptide SIFamide (SIFa) neurons in Drosophila melanogaster have been characterized by their exceptionally elaborate arborization patterns, which extend from the brain into the ventral nerve cord (VNC). SIFa neurons are equipped to receive signals that integrate both internal physiological cues and external environmental stimuli. These signals enable the neurons to regulate energy balance, sleep patterns, metabolic status, and circadian timing. These peptidergic neurons are instrumental in orchestrating the animal's internal states and refining its behavioral responses, yet the precise molecular underpinnings of this process remain elusive. Here, we demonstrate that SIFa neurons coordinate a range of behavioral responses by selectively integrating inputs and outputs in a context-dependent manner. These neurons engage in a feedback loop with sNPF neurons in the VNC, modifying behaviors such as longer mating duration (LMD) and shorter mating duration (SMD). Additionally, SIFa neurons interact with dopamine and glutamate to differentially regulate sleep and mating duration. Activating SIFa neurons leads to reduced mating duration and increased food intake, while deactivating them reduces food intake. Overall, these findings demonstrate the importance of SIFa neurons in absorbing inputs and turning them into behavioral outputs, shedding light on animal's intricate behavioral orchestration.

  • Could psychedelics be fine-tuned to relieve anxiety but skip the ‘trip’?

    Nature · 2025-02-18

    articleSenior authorCorresponding

Frequent coauthors

  • Yulong Li

    Peking University

    28 shared
  • Alfred P. Kaye

    National Center for PTSD

    23 shared
  • Pasha A. Davoudian

    Yale University

    18 shared
  • Ling-Xiao Shao

    Cornell University

    16 shared
  • Huriye Atilgan

    Yale University

    16 shared
  • Clara Liao

    Cornell University

    15 shared
  • Jiesi Feng

    Peking University

    14 shared
  • Farhan Ali

    14 shared

Labs

Education

  • Other, Physical Therapy

    University of Southern California

    2015
  • B.S., Kinesiology

    University of Southern California

    2011

Awards & honors

  • Certified Wound Specialist (CWS) through the American Board…
  • Certified clinical instructor through APTA since 2005
  • Resume-aware match score
  • Save to shortlist
  • AI-drafted outreach

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