About

Kafui Dzirasa is the A. Eugene and Marie Washington Presidential Distinguished Professor of Psychiatry and Behavioral Sciences at Duke University. He holds additional appointments as a Professor in Neurobiology, Neurosurgery, and Biomedical Engineering, and is an Investigator in the Duke Institute for Brain Sciences. His educational background includes a Ph.D. and M.D. from Duke University, with training as a Resident in Psychiatry at Duke University School of Medicine. His research focuses on understanding the neural mechanisms underlying psychiatric disorders, utilizing electrical brain circuit editing, brain-wide electrical dynamics, and computational models to explore mental health and disease. Dzirasa has contributed to advancing the understanding of brain networks related to emotion regulation, stress, and mental illness, and is recognized for his efforts to address systemic racism in scientific funding and promote diversity in neuroscience. His work has earned him numerous honors, including election to the National Academy of Medicine and fellowship in the American Institute for Medical and Biological Engineering.

Research topics

• Sociology
• Political Science
• Biology
• Psychology
• Genetics
• Social Science
• Gender studies
• Neuroscience
• Medicine
• Cognitive psychology
• Internal medicine
• Medical education
• Environmental ethics
• Engineering ethics
• Law
• Physiology
• Gerontology
• Family medicine
• Demography

Selected publications

• Long-term editing of brain circuits using an engineered electrical synapse

  Nature · 2026-05-13

  articleOpen accessSenior authorCorresponding

  Electrical signalling across distinct populations of brain cells underpins cognitive and emotional function. However, approaches that selectively regulate electrical signalling between two cellular components of a mammalian neural circuit remain sparse. Here we engineered an electrical synapse composed of two connexin proteins1 found in Morone americana (white perch fish)—connexin 34.7 and connexin 35—to accomplish mammalian circuit modulation. By exploiting protein mutagenesis, devising a new in vitro system for assaying connexin hemichannel docking, and performing computational modelling of hemichannel interactions, we uncovered a structural motif that contributes to electrical synapse formation. Targeting this motif, we designed connexin 34.7 and connexin 35 hemichannels that dock with each other to form an electrical synapse but not with other major connexins expressed in the mammalian central nervous system. We validated this electrical synapse in vivo using worms (Caenorhabditis elegans) and mice (Mus musculus). We demonstrate that it can strengthen communication across neural circuits composed of pairs of distinct cell types and modify behaviour accordingly. Thus, we establish ‘long-term integration of circuits using connexins’ (LinCx) for precision circuit editing in mammals. Connexin proteins found in white perch fish were used to engineer synthetic electrical synapses, enabling precision circuit editing in mammals.

  PublisherDOI

• RNA exosome-mediated RNA surveillance governs developmental timing in the human cerebellum

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

  articleOpen access

  Defects in RNA metabolism are a defining feature of neurodevelopmental disease, yet how RNA decay pathways contribute to human brain development remains poorly understood. Mutations in ubiquitously expressed RNA surveillance factors often cause highly tissue-selective disease, highlighting a central paradox in human biology. The RNA exosome is a conserved ribonuclease complex traditionally viewed as a housekeeping machine for RNA turnover, yet recessive mutations in genes encoding structural subunits of the complex disproportionately cause neurological disease, suggesting an instructive role in nervous system development. Here, we show that the RNA exosome regulates the temporal progression of gene expression programs during human cerebellar differentiation. Using CRISPR-engineered human cerebellar organoids modeling EXOSC3 variants, we find that RNA exosome dysfunction does not broadly alter transcript abundance, but instead disrupts transitions between developmental states. Mutant organoids exhibit incomplete and mis-timed resolution of early transcriptional programs, altered lineage specificity, and impaired coordination of maturation-associated gene expression programs, with pronounced effects in neuronal lineages, particularly Purkinje cells and rhombic lip-derivatives. These defects are accompanied by disorganized laminar architecture and reduced coordination of neuronal activity, despite preserved intrinsic excitability. Together, our findings establish RNA surveillance as a key regulator of developmental timing, lineage fidelity, and neurodevelopmental disease.

  PublisherOA PDFDOI

• A widespread internal brain state for fentanyl withdrawal

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-08

  articleOpen accessSenior authorCorresponding

  ABSTRACT Opioid addiction is characterized by escalating drug use, driven in part by negative reinforcement from withdrawal, but the neural processes linking withdrawal to increased drug-taking remain poorly understood. Here, we use multisite local field potential recordings and interpretable machine learning to identify large-scale brain networks engaged by repeated opioid exposure and withdrawal. After discovering that repeated fentanyl exposure induces a progressively ramping network of widespread high beta and low gamma oscillations, we then identified a distinct brain network that selectively encodes the emergence and severity of opioid withdrawal. This network, termed EN-Withdrawal , is characterized by regional gamma oscillations and widely synchronized delta/theta oscillations. Its activity patterns predict the emergence of spontaneous and naloxone-precipitated withdrawal across multiple independent cohorts, generalizing across mice, sex, opioids, and dosing regimens, while persisting over multiple days of withdrawal. Using a novel, data-driven severity index, we find that network activity scales with individual behavioral severity without simply reflecting ongoing somatic behaviors or general aversion, suggesting that EN-Withdrawal underlies a withdrawal-induced internal state. Strikingly, network activity predicts the escalation of fentanyl self-administration on a mouse-by-mouse basis in experienced, but not drug-naïve, animals. These findings reveal a neurophysiological substrate of the negative reinforcement cycle of addiction that shapes individual vulnerability.

  PublisherDOI

• Illuminating consciousness

  Frontiers in Psychology · 2026-05-08

  articleOpen access

  What consciousness is, and how it relates to the body and nature at large, are among the most enduring questions in human history. Notable thinkers have long grappled with its definition, mechanisms, and purpose. In this review, we examine both historical and contemporary perspectives on consciousness across philosophy, science, medicine, and practice. By integrating diverse perspectives and lines of evidence, from neuroscientific models to clinical applications and contemplative methods, we aim to synthesize insights into a more holistic framework of consciousness. Our objective is two-fold: first, to identify common themes and persistent gaps in knowledge, and second, to highlight critical opportunities for future investigation. In doing so, we advance a working model of consciousness that considers how consciousness is constructed, how it can be measured and modified, and why it may be central not only to survival, but also to human flourishing.

  PublisherDOI

• Developing algorithmic psychiatry via multi-level spanning computational models

  Cell Reports Medicine · 2025-04-28 · 3 citations

  reviewOpen access

  Modern psychiatry faces challenges in translating neurobiological insights into treatments for severe illnesses. The mid-20th century witnessed the rise of molecular mechanisms as pathophysiological and treatment models, with recent holistic proposals keeping this focus unaltered. In this perspective, we explore how psychiatry can utilize systems neuroscience to develop a vertically integrated understanding of brain function to inform treatment. Using schizophrenia as a case study, we discuss scale-related challenges faced by researchers studying molecules, circuits, networks, and cognition and clinicians operating within existing frameworks. We emphasize computation as a bridging language, with algorithmic models like hierarchical predictive processing offering explanatory potential for targeted interventions. Developing such models will not only facilitate new interventions but also optimize combining existing treatments by predicting their multi-level effects. We conclude with the prognosis that the future is bright, but that continued investment in research closely driven by clinical realities will be critical.

  PublisherDOI

• Sex-specific regulation of microglial MyD88 in HMGB1-Induced anxiety phenotype in mice

  Neurobiology of Stress · 2025-03-23 · 4 citations

  articleOpen access

  Stress is a significant risk factor for the development and recurrence of anxiety disorders. Stress can profoundly impact the immune system, and lead to microglial functional alterations in the medial prefrontal cortex (mPFC), a brain region involved in the pathogenesis of anxiety. High mobility group box 1 protein (HMGB1) is a potent pro-inflammatory stimulus and danger-associated molecular pattern (DAMP) released from neuronal and non-neuronal cells following stress. HMGB1 provokes pro-inflammatory responses in the brain and, when administered locally, alters behavior in the absence of other stressors. In this study, we administered dsHMGB1 into the mPFC of male and female mice for 5 days to investigate the cellular and molecular mechanisms underlying HMGB1-induced behavioral dysfunction, with a focus on cell-type specificity and potential sex differences. Here, we demonstrate that dsHMGB1 infusion into the mPFC elicited behavior changes in both sexes but only altered microglial morphology robustly in female mice. Moreover, preventing microglial changes with cell-specific ablation of the MyD88 pathway prevented anxiety-like behaviors only in females. These results support the hypothesis that microglial MyD88 signaling is a critical mediator of HMGB1-induced stress responses, particularly in adult female mice. • Infusion of HMGB1 to PFC causes behavioral changes in male and female adult mice. • Females demonstrate a more robust increase in microglial reactivity in response to HMGB1 administration. • Conditional knockout of MyD88 prevents changes in behavior and microglial reactivity in females in response to HMGB1.

  PublisherDOI

• Juneteenth in STEMM and the barriers to equitable science

  UNC Libraries · 2025-03-19

  articleOpen access
  PublisherDOI

• Long-term editing of brain circuits in mice using an engineered electrical synapse

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-26 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Abstract Electrical signaling across distinct populations of brain cells underpins cognitive and emotional function; however, approaches that selectively regulate electrical signaling between two cellular components of a mammalian neural circuit remain sparse. Here, we engineered an electrical synapse composed of two connexin proteins found in Morone americana (white perch fish) – connexin34.7 and connexin35 – to accomplish mammalian circuit modulation. By exploiting protein mutagenesis, devising a new in vitro system for assaying connexin hemichannel docking, and performing computational modeling of hemichannel interactions, we uncovered a structural motif that contributes to electrical synapse formation. Targeting these motifs, we designed connexin34.7 and connexin35 hemichannels that dock with each other to form an electrical synapse, but not with other major connexins expressed in the mammalian central nervous system. We validated this electrical synapse in vivo using C. elegans and mice, demonstrating that it can strengthen communication across neural circuits composed of pairs of distinct cell types and modify behavior accordingly. Thus, we establish ‘ L ong-term in tegration of C ircuits using conne x ins’ (LinCx) for precision circuit-editing in mammals.

  PublisherOA PDFDOI

• Methods for In Vivo Circuit Analysis

  2025-01-01

  book-chapter

  Abstract Breakthroughs in understanding neural circuit activity hold much promise for developing next-generation therapeutics for psychiatric disorders. Determination of how dynamic activity is coordinated across brain regions to effect specific behavioral function (or dysfunction) has the capacity to enable the development of therapeutics with increased specificity and fewer side effects. This chapter discusses the advantages and limitations of different methodologies for measuring and manipulating neural circuit activity in humans and in animal models. Methodologies that can be carried out in humans include functional magnetic resonance imaging; functional near-infrared spectroscopy; positron emission tomography; magnetoencephalography; and electroencephalography, including scalp and intracranial electroencephalography. Methodologies used specifically in animal models include in vivo electrophysiology, fiber photometry, and microendoscopy. Targeted neural circuit manipulations combined with these measurements are already being applied to a wide range of experimental and therapeutic strategies that illuminate routes to circuit-based treatments for complex brain disorders.

  PublisherDOI

• Synaptic editing of frontostriatal circuitry prevents excessive grooming in SAPAP3-deficient mice

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-29

  preprintOpen accessSenior authorCorresponding

  Synaptic dysfunction has been implicated as a key mechanism underlying the pathophysiology of psychiatric disorders. Most pharmacological therapeutics for schizophrenia, autism spectrum disorder, obsessive-compulsive disorder, and major depressive disorder temporarily augment chemical synapse function. Nevertheless, medication non-compliance is a major clinical challenge, and behavioral dysfunction often returns following pharmacotherapeutic discontinuation. Here, we deployed a designer electrical synapse to edit a single class of chemical synapses in a genetic mouse model of obsessive-compulsive disorder (OCD). Editing these synapses in juvenile mice normalized circuit function and prevented the emergence of pathological repetitive behavior in adulthood. Thus, we establish precision circuit editing as a putative strategy for preventative psychotherapeutics.

  PublisherOA PDFDOI

Recent grants

• MULTIREGIONAL ELECTRICAL ENCODING OF SOCIAL AGGRESSION

  NIH · $2.9M · 2021–2026

• Dissecting and modifying temporal dynamics underlying major depressive disorder

  NIH · $3.4M · 2019–2024

• Environmental Toxins and Microglia-Synapse Interactions in Autism

  NIH · $2.1M · 2016–2021

• NIH Grant R01MH099192

  NIH · $2.2M · 2018

Frequent coauthors

• David Carlson

  94 shared

• Stephen D. Mague

  90 shared

• Sunil Kumar

  86 shared

• Dalton Hughes

  Howard Hughes Medical Institute

  75 shared

• Neil M. Gallagher

  Cornell University

  73 shared

• Rainbo Hultman

  University of Iowa

  66 shared

• Marc G. Caron

  Duke University Hospital

  62 shared

• Cameron Blount

  Walter Reed Army Institute of Research

  58 shared

Education

• General Residency, Psychiatry and Behavioral Science

  Duke Medicine

  2016

• MD, School of Medicine

  Duke Medicine

  2009

• PhD, Neurobiology

  Duke University

  2007

• BS, Chemical Engineering

  University of Maryland, Baltimore County

  2001

Awards & honors

• College of Fellows. American Institute for Medical and Biolo…
• HHMI Investigator. Howard Hughes Medical Institute (2021)
• Elected Member. National Academy of Medicine (2021)