BBSP Faculty

Laminar organization of neurons in cerebral cortex is critical for normal brain function. Two distinct cellular events guarantee the emergence of laminar organization– coordinated sequence of neuronal migration, and generation of radial glial cells that supports neurogenesis and neuronal migration. Our goal is to understand the cellular and molecular mechanisms underlying neuronal migration and layer formation in the mammalian cerebral cortex. Towards this goal, we are studying the following three related questions: 1. What are the signals that regulate the establishment, development and differentiation of radial glial cells, a key substrate for neuronal migration and a source of new neurons in cerebral cortex?2. What are the signals for neuronal migration that determine how neurons reach their appropriate positions in the developing cerebral cortex?3. What are the specific cell-cell adhesion related mechanisms that determine how neurons migrate and coalesce into distinct layers in the developing cerebral cortex?

Building a functioning brain requires an elaborate network of interactions between neurons and glia. We use mouse genetics, primary cell culture, quantitative proteomics, molecular biology, and super resolution microscopy to study glial cells during brain development. We are particularly interested in how astrocytes acquire their complex morphology and communicate with neighboring astrocytes, neurons, and oligodendrocytes. Furthermore, we are investigating how glial dysfunction drives the pathogenesis of brain disorders such as autism, schizophrenia, and leukodystrophy.

What if you can target and deliver a drug directly to the side of disease in the body? It is possible, when you use smart living creatures pro-inflammatory response cells, such as monocytes, T-lymphocytes or dendritic cells. You can load these cells with the drug and inject these carriers into the blood stream. They will migrate to the inflammation site (for example, across the blood brain barrier) and release the drug. Thus, you can reduce the inflammation and protect the cells (for example, neurons) in patients with Parkinson’s and Alzheimer diseases.

My Lab focuses on studies of neural circuits underlying attention, executive function and stress response in the human brain, as well as the breakdown in these functions in neuropsychiatric and neurodevelopment disorders such as schizophrenia, substance abuse, depression and autism. We are particular interested in identifying neural precursors and predictors of illness in high-risk adolescents, including risk for psychosis, mood disorders and substance abuse. Our research uses multimodal imaging integrating functional magnetic resonance imaging, electrophysiological scalp recording, experimental psychology and neuropsychological assessment techniques to explore the behavioral and neurophysiological dimensions of information processing. Much of the current work focuses on mapping the role of stress neurobiology in predicting severity of anxiety and anhedonia in adolescents and procuring risk for severe psychiatric developmental disorders.

Research in my lab examines the neurobiological mechanisms underlying alcoholism and addiction. At present studies are focused on the interaction between stress-related systems and sensitivity to alcohol, in order to better understand the mechanisms that underlie increased alcohol drinking during stressful episodes. We use an array of behavioral (e.g., operant self-administration, drug discrimination) and behavioral pharmacology techniques, including targeted brain regional drug injections, to functionally evaluate the role of specific molecular targets. In parallel to the behavioral studies, we use immunohistochemistry and Western blot techniques to examine alterations in the expression of various molecular targets following stress exposure. We are also applying these techniques to examine and integrate the study of depression that emerges following stress hormone exposure.

My lab uses a cognitive neuroscience approach to understand the neurobiology of drug addiction in humans. The tools we use include fMRI, cognitive testing, physiological monitoring, pharmacology, and genetic testing. We specifically seek to determine 1) how the brain learns new stimulus-response associations and replaces learned associations, 2) the neurobiological mechanisms underlying the tendency to select immediate over delayed rewards, and 3) the neural bases of addiction-related attentional bias.

The Brenman lab studies how a universal energy and stress sensor, AMP-activated protein kinase (AMPK) regulates cellular function and signaling. AMPK is proposed to be a therapeutic target for Type 2 diabetes and Metabolic syndrome (obesity, insulin resistance, cardiovascular disease). In addition, AMPK can be activated by LKB1, a known human tumor suppressor. Thus AMPK signaling is not only relevant to diabetes but also cancer. We are interested in molecular genetic and biochemical approaches to understand how AMPK contributes to neurodegeneration, metabolism/cardiac disease and cancer.

Research in the Carelli laboratory is in the area of behavioral neuroscience. Our studies focus on the neurobiological basis of motivated behaviors, including drug addiction. Electrophysiology and electrochemistry procedures are used during behavior to examine the role of the brain ‘reward’ circuit in natural (e.g., food) versus drug (e.g., cocaine) reward. Studies incorporate classical and operant conditioning procedures to study the role of the nucleus accumbens (and dopamine) and associated brain regions in learning and memory, as they relate to motivated behaviors.

The goal of our research is to understand how astrocytes develop and how they interact with neural elements during nervous system formation, function, and maintenance. Our lab uses fruit fly Drosophila and zebrafish Danio rerio to explore fundamental aspects of astrocyte biology. We leverage the powerful genetics and unparalleled molecular toolsets in flies to uncover gene function, and we exploit the advanced live-imaging techniques in zebrafish to study astrocyte-neuron interactions in vivo.

Our goal is to understand the fundamental cell biology underlying processes such as neurodevelopment, angiogenesis, and the metastasis of cancer cells. Most of our experiments focus on molecular motors such as myosin-X and on the finger-like structures known as filopodia. We generally utilize advanced imaging techniques such as TIRF and single-molecule imaging in conjunction with mammalian cell culture. We also use molecular biology and biochemistry and are in the process of developing a mouse model to investigate the functions of myosin-X and filopodia. We are looking for experimentally driven students who have strong interests in understanding the molecular basis of dynamic cellular processes such as filopodial extension, mechanosensing, and cell migration.

The Cohen Lab investigates how functional brain networks in humans interact and reconfigure when confronted with changing cognitive demands, when experiencing transformations across development, and when facing disruptions in healthy functioning due to disease. We are also interested in how this neural flexibility contributes to flexibility in control and the ability to learn, as well as the consequences of dysfunction in this flexibility. We use behavioral, neuroimaging, and clinical approaches taken from neuroscience, psychology, and mathematics to address our research questions.

My research aims to uncover the molecular aspects of protein aggregation diseases (also called PAD) which include neurodegenerative diseases (such as Alzheimer’s disease and Amyotrophic Lateral Sclerosis), myofibrillar myopathies (such as muscular dystrophies), as well as the formation of age-related cataracts.  Although very distinct, these disorders share a common underlying pathogenic mechanism.  Using a combination of biochemistry and in vitro approaches, cell biology, and primary cells / transgenic mouse models, we will investigate the post-translational modifications (PTMs) that drive these disease processes. Ultimately, this research will provide a platform for future drug discovery efforts against these devastating diseases.

Lipids are crucial molecules for life. They play important roles in building membranes, storing energy, and cell signaling. We are interested in how lipids move around both within cells and between cells, for example from astrocytes to neurons. The lab uses cutting-edge microscopy techniques including live-cell imaging, superresolution microscopy, and multispectral imaging. We use these approaches to understand how defects in lipid trafficking contribute to metabolic and neurodegenerative diseases.

The overriding goal of Dr. Coleman’s work is to identify novel treatments for alcohol use disorders (AUD) and associated peripheral disease pathologies. Currently, this includes: the role of neuroimmune Signaling in AUD pathology, the role of alcohol-associated immune dysfunction in associated disease states, and novel molecular and subcellular mediators of immune dysfunction such as extracellular vesicles, and regenerative medicine approaches such as microglial repopulation.

The Cyr laboratory studies cellular mechanisms for cystic fibrosis and prion disease. We seek to determine how protein misfolding leads to the lung pathology associated with Cystic Fibrosis and the neurodegeneration associated with prion disease.

Our lab studies brain network connectivity in the healthy brain and in neurological and neuropsychiatric patient populations. We focus on the organizational, dynamical, and computational properties of large-scale brain networks and determine how these properties contribute to human behavior in health and disease. We strive to advance the basic understanding of brain structure and function, while making discoveries that can be translated to clinical practice.

We study how mammalian cells regulate their survival and death (apoptosis). We have focused our work on identifying unique mechanisms by which these pathways are regulated in neurons, stem cells, and cancer cells. We utilize various techniques to examine this in primary cells as well as in transgenic and knock out mouse models in vivo. Our ultimate goal is to discover novel cell survival and death mediators that can be targeted for therapy in neurodegeneration and cancer.

Sleep is an essential and evolutionarily conserved process that modifies synapses in the brain to support cognitive functions such as learning and memory. We are interested in understanding the molecular mechanisms of synaptic plasticity with a particular interest in sleep. Using mouse models of human disease as well as primary cultured neurons, we are applying this work to understanding and treating neurodevelopmental disorders including autism and intellectual disability. The lab focuses on biochemistry, pharmacology, animal behavior and genetics.

Humans have a remarkable ability to learn from their environment after birth, but this plasticity also makes them susceptible to environmental insults.  At the cellular level, learning is accomplished by changing the strength of the synaptic connections between neurons.  Therefore, the Dudek lab is working to identify the underlying processes of synaptic plasticity.  Using molecular techniques, patch clamp recordings and confocal microscopic imaging from neurons in brain slices and culture, we ask how neuronal activity controls gene transcription and brain circuitry and what determines why some brain regions are more plastic than others.  These studies are likely to shed light on environmental causes of psychiatric diseases such as schizophrenia and autism.

Our lab studies the underlying structural and functional substrates of behavior in disease using rodent models. Specifically our goal is to develop a better understanding of how cellular function in the CNS is affected by drug-related substances (opioids, cannabinoids) in the context of HIV infection. That includes the study of how drugs of abuse exacerbate the pathogenesis of neuroAIDS but also the study of targets within the endocannabinoid system for the potential treatment of HIV. We use various in vivo and in vitro techniques, including primary cell culture models, behavioral conditioning tasks, live cell imaging, and electrophysiology.

Our goal is to revolutionize the treatment of psychiatric and neurological illness by developing novel brain stimulation paradigms. We identify and target network dynamics of physiological and pathological brain function. We combine computational modeling, optogenetics, in vitro and in vivo electrophysiology in animal models and humans, control engineering, and clinical trials. We strive to make our laboratory a productive, collaborative, and happy workplace.

Dr. Gilmore’s research group is applying state-of–the-art magnetic resonance imaging and image analysis techniques to study human brain development in 0-6 year olds.  Approaches include structural, diffusion tensor, and resting state functional imaging, with a focus on cortical gray and white matter development and its relationship to cognitive development.  Studies include normally developing children, twins, and children at high risk for schizophrenia and bipolar illness.  We also study the contributions of genetic and environmental risk factors to early brain development in humans.  A developing collaborative project with Flavio Frohlich, PhD will use imaging to study white and gray matter development in ferrets and its relationship with cortical oscillatory network development.

My research combines behavioral, patient-based, and functional neuroimaging approaches to investigate the cognitive neuroscience of human learning and memory. My primary research focus is in elucidating the cognitive processes and neural mechanisms mediating relational memory – the form of memory which represents relationships among items or informational elements. In everyday life, relational memory processes play a critical role in linking or binding together the various cognitive, affective, and contextual components of a learning event into an integrated memory trace. I am interested in exploring the cognitive and neural processes mediating relational memory in young adults and examining how these processes change with healthy aging and neurodegenerative disease (particularly Alzheimer’s disease).

Fundamentally, our research is focused on how the nervous and immune systems are developmentally educated by infectious and non-infectious stressors across the “gum-to-gut” axis. One current major focus of the lab is to elucidate how early life stress impacts the developing gut and dentition using zebrafish as an ideal — and translational — model organism. We utilize a combination of advanced imaging, next-generation sequencing, and genetic approaches to achieve a greater understanding of how early life events dictate health outcomes across the lifespan and generations. In addition to these primary research interests, we maintain active collaborations with other groups within the Adams School of Dentistry and across campus.

During cell shape change and motility, a dynamic cytoskeleton produces the force to initiate plasma membrane protrusion, while vesicle trafficking supplies phospholipids and membrane proteins to the expanding plasma membrane. Extracellular cues activate intracellular signaling pathways to elicit specific cell shape changes and motility responses through coordinated cytoskeletal dynamics and vesicle trafficking. In my lab we are investigating the role of two ubiquitin ligases, TRIM9 and TRIM67, in the cell shape changes that occur during neuronal development. We utilize a variety techniques including high resolution live cell microscopy, gene disruption, mouse models, and biochemistry to understand the complex coordination of cytoskeletal dynamics and membrane trafficking driving neuronal shape change and growth cone motility in primary neurons.

The Hantman Lab is interested in how functions emerge from network activity in the nervous system. Particularly, we study how the nervous system generates patterns of activity that control our bodies in the world. Our approach combines genetics, anatomy, physiology, perturbations, and a dynamical systems approach.

The Neurotoxicology Group examines the role of microglia interactions with neurons and the associated immune-mediated responses in brain development and aging as they relate to the initiation of brain damage, the progression of cell death, and subsequent repair/regenerative capabilities.  We have an interest in the neuroimmune response with regards to neurodegenerative diseases such as, Alzheimer’s disease.

Research in my laboratory focuses on the effects of air pollution and other environmental pollutants on the cardiovascular and respiratory systems. We use both traditional as well as novel physiological approaches (radiotelemetry, HF echocardiography, physiological challenge testing) to determine not only the short-term effects of exposure, but also the long-term consequences on health, particularly in the development of chronic diseases (e.g. heart disease). Rodent models are used to study the effects of real-world air pollution concentrations on the central and local neural controls of the cardiovascular and respiratory systems that render a host susceptible to adverse health events. Newer exciting research is focused on public health aspects such as nutrition (e.g. vitamin deficiencies) and non-environmental stressors (e.g. noise, climate change, social disruption) as modifiers of air pollution health effects. These studies examine the epigenetic changes that occur in early life or during development that result in physiological effects and future susceptibility.

My research interests involve the structure of inhibitory neuronal networks and how these networks change to produce adverse behavioral outcomes. My main interest is how the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) regulates neuronal networks via both synaptic and extrasynaptic forms of inhibition and how alterations in inhibitory networks contribute to clinical conditions such as alcohol use disorder, nicotine, addiction, or stress. My work has focused primarily on three brain regions: the nucleus tractus solitaries (NTS), central and basolateral amygdala, and ventral tegmental area. In each of these areas I have identified local inhibitory networks that control overall excitability and that are dysregulated by exposure to acute and or chronic exposure to alcohol or nicotine.

Flexibility of the brain allows the same sensory cue to have very different meaning to the animal depending on past experience (i.e. learning and memory) or current context. Our goal is to understand this process at the levels of synaptic plasticity, neural circuit and behavior. Our model system is a simple brain of the fruit fly, Drosophila. We employ in vivo electrophysiology and two-photon calcium imaging together with genetic circuit manipulation. Taking advantage of this unique combination, we aim to find important circuit principles that are shared with vertebrate systems.

Our preclinical research is based on the concept that drugs of abuse gain control over behavior by hijacking molecular mechanisms of neuroplasticity within brain reward circuits. Our lab focuses on three main research questions: (1) Discover the neural circuits and molecular mechanisms that mediate the reinforcing and pleasurable subjective effects of alcohol and other drugs, (2) Identify the long-term effects of cocaine and alcohol abuse during adolescence, (3) Identify novel neural targets and validate pharmacological compounds that may be used to treat problems associated with alcohol and drug abuse. The lab culture is collaborative and dynamic, innovative, and team-based. We are looking for colleagues who share an interest in understanding how alcohol hijacks reward pathways to produce addiction.

Antiretroviral therapy (ART) is effective in suppressing HIV-1 replication in the periphery, however, it fails to eradicate HIV-1 reservoirs in patients. The main barrier for HIV cure is the latent HIV-1, hiding inside the immune cells where no or very low level of viral particles are made. This prevents our immune system to recognize the latent reservoirs to clear the infection. The main goal of my laboratory is to discover the molecular mechanisms how HIV-1 achieves its latent state and to translate our understanding of HIV latency into therapeutic intervention.

Several research programs are undertaking in my lab with a focus of epigenetic regulation of HIV latency, including molecular mechanisms of HIV replication and latency establishment, host-virus interaction, innate immune response to viral infection, and the role of microbiome in the gut health. Extensive in vitro HIV latency models, ex vivo patient latency models, and in vivo patient and rhesus macaque models of AIDS are carried out in my lab. Multiple tools are applied in our studies, including RNA-seq, proteomics, metabolomics, highly sensitive digital droplet PCR and tissue RNA/DNAscope, digital ELISA, and modern and traditional molecular biological and biochemical techniques. We are also very interested in how non-CD4 expression cells in the Central Nervous System (CNS) get infected by HIV-1, how the unique interaction among HIV-1, immune cells, vascular cells, and neuron cells contributes to the initial seeding of latent reservoirs in the CNS, and whether we can target the unique viral infection and latency signaling pathways to attack HIV reservoirs in CNS for a cure/remission of HIV-1 and HIV-associated neurocognitive disorders (HAND). We have developed multiple tools to attack HIV latency, including latency reversal agents for “Shock and Kill” strategy, such as histone deacetylase inhibitors and ingenol family compounds of protein kinase C agonists, and latency enforcing agents for deep silencing of latent HIV-1. Several clinical and pre-clinical studies are being tested to evaluate their potential to eradicate latent HIV reservoirs in vivo. We are actively recruiting postdocs, visiting scholars, and technicians. Rotation graduate students and undergraduate students are welcome to join my lab, located in the UNC HIV Cure Center, for these exciting HIV cure research projects.

We use studies of HIV/SIV evolution to reveal information about viral dynamics in vivo. This typically involves genetic and/or phenotypic analyses of viral populations in samples from HIV-infected humans or SIV-infected nonhuman primates (NHPs). We are currently exploring the mechanisms that contribute to neurocognitive impairment in HIV-infected people by sequencing viral populations in the CNS of humans and NHPs not on antiretroviral therapy. We are also using these approaches to examine viral populations that persist during long-term antiretroviral therapy in an effort to better understand the viral reservoirs that must be targeted in order to cure HIV-infected people.

Emotional behavior is regulated by a host of chemicals, including neurotransmitters and neuromodulators, acting on specific circuits within the brain. There is strong evidence for the existence of both endogenous stress and anti-stress systems. Chronic exposure to drugs of abuse and stress are hypothesized to modulate the relative balance of activity of these systems within key circuitry in the brain leading to dysregulated emotional behavior. One of the primary focuses of the Kash lab is to understand how chronic drugs of abuse and stress alter neuronal function, focusing on these stress and anti-stress systems in brain circuitry important for anxiety-like behavior. In particular, we are interested in defining alterations in synaptic function, modulation and plasticity using a combination of whole-cell patch-clamp physiology, biochemistry and mouse models.  Current projects are focused on the role of a unique population of dopamine neurons in alcoholism and anxiety.

Our primary goal is to identify how our brain processes sound inputs to detect complex patterns, such as our language. Using mouse auditory cortex as a model system, we combine multiple cutting-edge techniques (e.g. in vivo whole-cell recording, two-photon calcium imaging, and optogenetics) in behaving animals to dissect the circuits that connect vocal inputs to behavioral outputs. Findings in the simple mouse cortex should provide a first step towards the ultimate understanding of the complex human brain circuits that enable verbal communication, and how they fail in psychiatric disorders.

Maintaining health and reducing disease-risk requires the brain to properly transduce signals across specialized regions and cell types. My lab studies neural signaling at the primary cilium, an antenna-like organelle that helps cells sense and respond to environmental cues. The function of primary cilia in the adult brain remains enigmatic. To probe cilia function, the lab will utilize mouse models, neural cultures, human brain samples, single-cell transcriptomics, proteomics, and microscopy. Ultimately, we aim to identify therapeutic targets for diseases like Alzheimer’s and Parkinson’s.

Trauma and stress are common in life. While most individuals recover following trauma/stress exposure, a substantial subset will go on to develop adverse neuropsychiatric outcomes such as chronic pain, posttraumatic stress disorder (PTSD), depression, and postconcussive symptoms. Our research is focused on understanding individual vulnerability to such outcomes and to identify novel biomarkers and targets for therapeutic intervention. We use translational research approaches, including bioinformatics analysis of large prospective human cohort data, animal model research, and systems and molecular biology to better understand pathogenic mechanisms. We are particularly interested in the genetic and psychiatric/social factors influencing adverse outcome development, as well as biological sex differences that contribute to higher rates of these outcomes in women vs men.

Our lab group is interested in the behavior, sensory ecology, neuroethology, and conservation biology of animals, particularly those that live in the ocean. Research focuses include: (1) physiology and ecology of animals that migrate long distances; (2) navigational mechanisms of sea turtles, spiny lobsters, monarch butterflies, and salmon; (3) neuroethology and behavioral physiology of invertebrate animals; (4) use of the Earth’s magnetic field in animal navigation; (5) technoethology (the use of novel computer and electronic technology to study behavior).

Psychoneuroimmunology; the effects of conditioning on lymphocyte reactivity

My research focuses on molecular mechanisms of mammalian nervous system development. We investigate mechanisms by which developing neurons migrate to the neocortex and form connections.

Our fundamental interest is in how the nervous system processes sensory information. We have been studying these problems using in vitro preparations that allow us to examine how single cells in the auditory cortex and auditory brainstem operate to integrate synaptic input, generate precisely timed action potentials, and adapt to changes in sensory input produced by hearing loss.  This has involved investigations into the kinds of ion channels expressed in particular subsets of cells, determination of the kinetics and voltage dependence of those channels, studies of synaptic transmission, and the generation of computational models that reflect our current understanding of how these cells operate and produce responses to acoustic stimuli.  A longstanding interest has been in the types of processing that take place in the elaborate network of cells in cerebral cortex. The structure and function of neurons in the auditory cortex depends extensively on sensory experience. We are now studying the functional spatial organization of auditory cortical neural networks at the level of connections between classes individual cells, using optical methods in normal mice and mice with noise-induced hearing loss.

Research in the McElligott lab focuses on the circuits and plasticity that underlie the development and manifestation of psychiatric illness, specifically disorders on the affective spectrum including alcohol use disorders, drug abuse and anxiety disorders. The lab has expertise in studying neurotransmission from the level of signaling in individual cells through behavior utilizing a variety of techniques including: whole-cell electrophysiology, in vivo and ex vivo fast-scan cyclic voltammetry (FSCV), circuit manipulations (optogenetics, chemogenetics, caspase ablation), and behavioral assays.  There are several ongoing projects in the lab. One area we are focused on explores the role of neurons in the central nucleus of the amygdala (CeA) that express the neuropeptide neurotensin and the role these neurons play in alcohol related phenotypes. Additionally we are interested in exploring how norepinephrine modulates neurotransmission within the brain and how the norepinephrine system itself is modulated in models of substance abuse and post-traumatic stress. Beyond these studies, we are actively engaged in several other collaborative projects with other labs at UNC, as well as around the world.

Dr. Meeker’s research is focused on the mechanisms of HIV neuropathogenesis and the development of therapeutic strategies for the treatment of neuroinflammation. Inflammatory changes within the brain caused by the viral infection initiate a toxic cascade that disrupts normal neural function and can eventually lead to neuronal death. To explore the mechanisms responsible for this damage, we investigate changes in calcium homeostasis, glutamate receptor function and inflammatory responses in primary neuronal, microglial and macrophage cultures. New therapeutic approaches targeted to signal transduction pathways and calcium regulation that protect the neurons and reduce inflammation are under investigation.

My laboratory has two main interests: 1) Regulation of P2Y receptor signaling and trafficking in epithelial cells and platelets. Our laboratory investigates the cellular and molecular mechanisms by which P2Y receptors are differentially targeted to distinct membrane surfaces of polarized epithelial cells and the regulation of P2Y receptor signaling during ADP-promoted platelet aggregation. 2) Antibiotic resistance mechanisms. We investigate the mechanisms of antibiotic resistance in the pathogenic bacterium, Neisseria gonorrhoeae. Our laboratory investigates how acquisition of mutant alleles of existing genes confers resistance to penicillin and cephalosporins. We also study the biosynthesis of the gonococcal Type IV pilus and its contribution to antibiotic resistance.

Our research focuses on the genetic and cellular mechanisms that underlie how prenatal exposure to alcohol and other drugs, such as cannabinoids, disrupt normal brain development. We use a wide variety of molecular and cell biology tools including RNA-seq (whole transcriptomic profiling), mouse transgenics, and confocal imaging to understand how drugs alter cell signaling pathways and transcriptional regulation in development. Our work also studies key regulatory pathways, such as Sonic hedgehog (Shh) and other primary cilia-mediated signals, during normal and aberrant embryonic development.

Our lab develops computer-driven optical instrumentation for applications in biology and neurosciences, beyond traditional imaging systems. Our research is interdisciplinary and welcomes backgrounds in optical engineering, computer sciences, biology or neurosciences. Our primary goal is to develop optical brain-machine interfaces and other technologies that use advanced light sources and detectors to probe and manipulate cellular functions deep into tissue at depths where traditional microscopy tools can no longer retrieve images.

My lab is driven to understand the neuronal pathologies underlying neurodevelopmental disorders, and to use this information to identify novel therapeutics.  We focus our research on monogenic autism spectrum disorders, including Angelman, Rett, and Pitt-Hopkins syndromes.  We employ a diverse number of techniques including: electrophysiology, molecular biology, biochemistry, mouse engineering, and in vivo imaging.

Research in our lab is focused on understanding how cocaine abuse affects glial cell physiology, in particular neuron-astrocyte communication.  We utilize the rat cocaine self-administration/reinstatement model, which allows us to test hypotheses regarding not only how chronic cocaine use affects properties of astrocytes and the tripartite synapse, but also how compounds affecting glial cells may influence synaptic processing within the brain’s reward neurocircuitry and behavioral measures of drug seeking.

The Robinson lab currently explores the neurodynamics of reinforcement pathways in the brain by using state-of-the-art, in vivo recording techniques in freely moving rats. Our goal is to understand the interplay of mesostriatal, mesocortical and corticostriatal circuits that underlie action selection, both in the context of normal development and function, and in the context of psychiatric disorders that involve maladaptive behavior, such as alcohol use disorder, adolescent vulnerability to drug use and addiction, cocaine-induced maternal neglect and binge-eating disorders.

Psychiatric disorders such as Anxiety and Autism Spectrum Disorders are often characterized by a rapid and amplified arousal response to stimuli (hyperarousal), which is often followed by a motivational drive to avoid such stimuli. Our lab studies the neuronal circuits that drive hyperarousal states by monitoring neuronal activity with single-cell precision using in vivo calcium imaging techniques in both head-fixed (two-photon microscopy) and freely-moving (miniature head-mounted microscopes) mice to record and track the activity of hundreds of individual neurons with both genetic and projection specificity.

The ultimate goal of our studies is to discover novel ways to treat human disease using G-protein coupled receptors.

Pain is a complex experience with sensory and emotional components. While acute pain is essential for survival, chronic pain is a debilitating disease accompanied by persistent unpleasant emotions. Efficient medications against chronic pain are lacking, and the absence of alternative to opioid analgesics has triggered the current Opioid Epidemic. Our lab studies how our nervous system generates pain perception, at the genetic, molecular, cellular, neural circuit, and behavioral levels. We also seek to understand how opioids alter activity in neural circuits to produce analgesia, but also side effects such as tolerance, addiction and respiratory depression. To this aim, we investigate the localization, trafficking and signaling properties of opioid receptors in neurons. These studies clarify pain and opioid mechanisms for identifying novel non-addictive drug targets to treat pain and strategies to dissociate opioid analgesia from deleterious effects.

The Schisler Lab is geared towards understanding and designing therapies for diseases involving proteinopathies- pathologies stemming from protein misfolding, aggregation, and disruption of protein quality control pathways. We focus on cardiovascular diseases including the now more appreciated overlap with neurological diseases such as CHIPopathy (or SCAR16, discovered here in our lab) and polyQ diseases. We use molecular, cellular, and animal-based models often in combination with clinical datasets to help drive our understanding of disease in translation to new therapies.

I am building a career in both clinical and translational research of brain tumors, primary and those resulting from metastasis. Clinically, I primarily see adult brain tumor patients and conduct/initiate clinical trials to meet the needs of this patient population. On the research side, I have a long-standing research interest in clinically-important membrane transport proteins. I conducted genetic and biochemical research on transporters, channels, and pumps during my doctoral research at the University of Cambridge, my postdoctoral study at Yale University, and various institutions (Yale, Johns Hopkins University, Cambridge) while training in medicine at Cambridge. Membrane transport proteins I have worked on include the proton-ATPase (mentor: C. Slayman) and the TAP transporter (mentor: P. Lehner), which are critical to antigen processing. After receiving my medical degree, I pursued advanced medical and additional research training in the U.S. (Johns Hopkins, Harvard) and received continuous funding from the NIH to pursue this research (NINDS-R25, NCI-K12, NINDS-K08). My first independent appointment as an Assistant Professor, Neuro-oncologist was at Emory University in 2016. At the University of Cincinnati, I was the Associate Director of the UC Brain Tumor Center and a recipient of the Harold C. Schott Endowed Chair.

At this time, my lab is focused on: (1) the development of a therapeutic approach for the treatment of primary and pediatric brain tumors, as well as cancers that commonly metastasize to the CNS (lung and melanoma); and (2) translation of technological advances that may impact treatment and quality of life in patients with cancer.

The Shiau Lab is integrating in vivo imaging, genetics, genome editing, functional genomics, bioinformatics, and cell biology to uncover and understand innate immune functions in development and disease. From single genes to individual cells to whole organism, we are using the vertebrate zebrafish model to reveal and connect mechanisms at multiple scales. Of particular interest are 1) the genetic regulation of macrophage activation to prevent inappropriate inflammatory and autoimmune conditions, and 2) how different tissue-resident macrophages impact vertebrate development and homeostasis particularly in the brain and gut, such as the role of microglia in brain development and animal behavior.

Dr. Shih is the Director of Small Animal Magnetic Resonance Imaging (MRI) at the Biomedical Research Imaging Center. His lab has implemented multi-model MRI techniques at high magnetic field to measure cerebral blood oxygenation, blood flow, blood volume, and oxygen metabolism changes in preclinical animal models. Dr. Shih’s lab is also developing simultaneous functional MRI (fMRI) and electrophysiology recording techniques at high spatial resolution to elucidate the pathophysiological mechanisms of neurovascular diseases. They will apply these techniques to (i) explore/validate functional connectivity network and neurovascular coupling in the rodent brain, (ii) study tissue characteristics after stroke, and (iii) investigate deep brain electrical stimulation, optogenetic stimulation, and pharmacogenetic stimulation in normal and Parkinsonian animal models.

Our lab examines cytoskeletal dynamics, the molecules that regulate it and the biological processes it is involved in using live cell imaging, in vitro reconstitution and x-ray crystallography.  Of particular interest are the microtubule +TIP proteins that dynamically localize to microtubule plus ends, communicate with the actin network, regulate microtubule dynamics, capture kinetochores and engage the cell cortex under polarity-based cues.

Our primary research interest is to identify the mechanisms that regulate neural circuit organization and function at distinct stages of adult neurogenesis, and to understand how circuit-level information-processing properties are remodeled by the integration of new neurons into existing circuits and how disregulation of this process may contribute to various neurological and mental disorders. Our long-range goals are to translate general principles governing neural network function into directions relevant for understanding neurological and psychiatric diseases. We are addressing these questions using a combination of cutting-edge technologies and approaches, including optogenetics, high-resolution microscopy, in vitro and in vivo electrophysiology, genetic lineage tracing and molecular biology.

We are a lab exploring how variations in the genome change the structure and development of the brain, and in doing so, create risk for neuropsychiatric illness. We study genetic effects on multiple aspects of the human brain, from macroscale phenotypes like gross human brain structure measured with MRI to molecular phenotypes like gene expression and chromatin accessibility measured with genome-sequencing technologies. We also use neural progenitor cells as a modifiable and high fidelity model system to understand how disease-associated variants affect brain development.

The Tarantino lab studies addiction and anxiety-related behaviors in mouse models using forward genetic approaches. We are currently studying a chemically-induced mutation in a splice donor site that results in increased novelty- and cocaine-induced locomotor activity and prolonged stress response. We are using RNA-seq to identify splice variants in the brain that differ between mutant and wildtype animals. We are also using measures of initial sensitivity to cocaine in dozens of inbred mouse strains to understand the genetics, biology and pharmacokinetics of acute cocaine response and how initial sensitivity might be related to addiction. Finally, we have just started a project aimed at studying the effects of perinatal exposure to dietary deficiencies on anxiety, depression and stress behaviors in adult offspring. This study utilizes RNA-seq and a unique breeding design to identify parent of origin effects on behavior and gene expression in response to perinatal diet.

Local mRNA translation is critical for axon regeneration, synapse formation, and synaptic plasticity. While much of research has focused on local translation in dendrites and in peripheral axons, less is known about local translation in smaller diameter central axons due to the technical difficulty of accessing them. We developed microfluidic technology to allow access to axons, as well as nascent boutons and fully functional boutons. We identified multiple transcripts that are targeted to cortical and hippocampal axons in rat (Taylor et al. J Neurosci 2009). Importantly, this work countered the prevailing view that local mRNA translation does not occur in mature axons. We are actively investigating transcripts in axons that may play a role in establishing proper synaptic connections. We are also using our technology to identify transcripts targeted to axons and boutons in human neurons. These studies are a critical step towards the identification of key genes and signaling molecules during synapse development, axonal regeneration, and proper circuit function.

My primary research interests are directed at the neurobiology of alcoholism. To study the central mechanisms involved with neurobiological responses to ethanol, I use both genetic and pharmacological manipulations. There are many factors that may cause an individual to progress from a moderate or social drinker to an alcoholic. In addition to environmental influences, there is growing evidence in both the human and animal literature that genetic factors contribute to alcohol abuse. Furthermore, the risk for developing alcoholism is likely not associated with a single gene, but rather with multiple genes that interact with environmental factors to determine susceptibility for uncontrolled drinking. Some of the questions that my laboratory is currently addressing are: 1) Does central neuropeptide Y (NPY) signaling modulate neurobiological responses to ethanol and ethanol consumption, 2) Do melanocortin peptides modulate ethanol intake? and 3) Does cAMP-dependent kinase (PKA) play a role in voluntary ethanol consumption and/or other effects produced by ethanol?

Social behavior is composed of a variety of distinct forms of interactions and is fundamental to survival. Several neural circuits must act in concert to allow for such complex behavior to occur and perturbations, either genetic and/or environmental, underlie many psychiatric and neurodevelopment disorders. The Walsh lab focuses on gaining an improved understanding of the biological basis of behavior using a multi-level approach to elucidate the molecular and circuit mechanisms underlying motivated social behavior. The goal of our research is to uncover how neural systems govern social interactions and what alterations occur in disease states to inform the development of novel therapeutics or treatment strategies.

One of the major focuses of the Walsh lab is on understanding how genetic mutations, as well as experience, lead to circuit adaptations that govern impaired behavior seen in mouse models of autism spectrum disorders (ASD). Our systems level analysis includes: 1) modeling these disorders with well described genetic markers, 2) defining causal relationships between activity within discrete anatomical structures in the brain that are critical to the physiology of the symptom under investigation (e.g. sociability), 3) performing deep characterization of the physiological profiles of these circuits and using that information to target specific receptors or molecules that may not have been considered for the treatment of specific ASD symptoms.

The vertebrate retina is an extension of the central nervous system that controls visual signaling and circadian rhythm.  Our laboratory is interested in how the retina adapts to changing light intensities in the natural environment.  We are presently studying the regulation of 2 G protein-coupled receptor kinases, GRK1 and GRK7, that participate in signal termination in the light-detecting cells of the retina, the rods and cones.  Signal termination helps these cells recover from light exposure and adapt to continually changing light intensities.  Recently, we determined that GRK1 and GRK7 are phosphorylated by cAMP-dependent protein kinase (PKA).  Since cAMP levels are regulated by light in the retina, phosphorylation by PKA may be important in recovery and adaptation.  Biochemical and molecular approaches are used in 2 model organisms, mouse and zebrafish, to address the role of PKA in retina function. Keywords:  cAMP, cone, G protein-coupled receptor, GPCR, GRK, kinase, neurobiology, opsin, PKA, retina, rhodopsin rod, second messenger, signal transduction, vision.

Early life and adult pain can have drastic effects on neurodevelopment and overall quality of life. In the Williams’ Pain, Aging, and Interdisciplinary Neurobehavioral (P.A.I.N.) Lab, our research focuses on behavioral neuroscience and the mechanisms of neurobiology and neurophysiology of pain processing, with a special emphasis on the neonatal. The ultimate research goal is to better understand, recognize, and alleviate pain in the newborn to improve the quality of life in adulthood by uncovering new assessment tools and interventional strategies. Our research interests include the mechanisms of neurobiology and neurophysiology of pain processing, neonatal pain, chronic pain, neurobehavior, osteoarthritis, translational medicine, anesthesia/analgesics, and evoked and non-evoked pain assessment tools. The P.A.I.N. Lab has both pre-clinical and clinical studies to help close the gap in translation.

We try to bridge the gap between genetic risk factors for psychiatric illnesses and neurobiological mechanisms by decoding the regulatory relationships of the non-coding genome. In particular, we implement Hi-C, a genome-wide chromosome conformation capture technique to identify the folding principle of the genome in human brain. We then leverage this information to identify the functional impacts of the common variants associated with neuropsychiatric disorders.

The EnYang Lab explores interdisciplinary fields to unravel the intricate workings of neural networks within the brain, focusing on how they execute computations, foster imagination, and respond to emotional states. Using larval zebrafish as an animal model, the lab observes, decodes, and perturbs the entire neural networks at single-cell resolution during cognitive tasks. Through the integration of whole-brain imaging, brain-machine interface (BMI), Virtual Reality, optogenetic manipulation, deep learning, and other modern technologies, the lab aims to decipher cognitive abilities in the brain and translate findings into engineering solutions, potentially impacting fields like learning disorders and psychiatric management.

Our research is focused on two general areas:  1. Autism and 2. Pain.  Our autism research is focused on topoisomerases and other transcriptional regulators that were recently linked to autism.  We use genome-wide approaches to better understand how these transcriptional regulators affect gene expression in developing and adult neurons (such as RNA-seq, ChIP-seq, Crispr/Cas9 for knocking out genes).  We also assess how synaptic function is affected, using calcium imaging and electrophysiology.   In addition, we are performing a large RNA-seq screen to identify chemicals and drugs that increase risk for autism.   /  / Our pain research is focused on lipid kinases that regulate pain signaling and sensitization.  This includes work with cultured dorsal root ganglia (DRG) neurons, molecular biology and behavioral models of chronic pain.  We also are working on drug discovery projects, with an eye towards developing new therapeutics for chronic pain.