Department of
Neuroscience

2017 SURI Mentors

Sadie Bergeron, PhD 
Assistant Professor in Biology

The Bergeron Lab is investigating how specific molecular genetic pathways and distinct environmental contexts contribute to altered brain development and function in zebrafish with regard to neurodevelopmental disorders in humans in which patients typically have altered sensory processing (i.e. ASD, schizophrenia). Previous work has linked the transcription factor, gsx1, to the development of neurons in mouse and zebrafish that are important for normal sensory processing in a behavioral paradigm that reveals disrupted acoustic startle responsiveness in human patients with schizophrenia. Our lab seeks to identify the neuroanatomical changes that are present upon loss ofgsx1 and the gene that it is most closely related to, gsx2, as all of the unique and overlapping roles that these two transcription factors have across the different brain regions in which they are expressed have yet to be determined. We also wish to characterize changes in sensory driven behaviors upon loss of these two transcription factors; primarily visual/light-mediated and auditory. It is also our long-term goal to identify transcriptional targets of gsx1 and gsx2 to know if any of these are disease related genes in humans. Techniques our lab uses include zebrafish husbandry, behavioral testing in an animal model system, microscopy (light, fluorescence, confocal), in situhybridization to detect mRNA expression, immunohistochemistry, working with DNA and RNA molecules (extracting from tissue, in vitro transcription, molecular cloning), PCR, RT-PCR, FACS, agarose gel electrophoresis and imaging, and fragment analysis. It is widely known that the developing brain is shaped by a combination of both genetic and environmental factors, however the mechanisms that dictate the consequences of the interactions of these two factors at the cellular and molecular levels are still largely unknown. The zebrafish is an emerging model system for studies or neurodevelopmental disorders in humans at the cellular, molecular, and behavioral levels. Its value is in their rapid development and transparency for imaging. They also share ~70% of their genes with humans and many analogous brain structures by their neuroanatomical position and function at just 6 days old.

Potential projects include:

  1. Examine markers of neuronal differentiation, neurotransmitter identity, cell proliferation and survival in the developing brain of zebrafish mutants for the transcription factors gsx1 and gsx2
  2. (2)  Develop and validate new tools to genetically isolate distinct populations of gsx1 and gsx2 neural progenitors.

Julie Brefczynski- Lewis, PhD 
Research Assistant Professor of Physiology & Pharmacology

In the Brefczynski-Lewis lab, we are examining the relationship between mental and physical health and how stress reliving exercises can affect both. We utilize a variety of multimodal techniques such as fMRI, heart rate variability, cortisol measures and a novel brain imaging device called AMPET, the wearable PET scanner.  The latter is a part of a BRAIN initiative project that involves novel techniques for imaging the human brain. Although the summer project will emphasize the testing of a stress coping Smartphone app on heart rate and other measures when faced with real world stress, summer students will get a taste of imaging with this completely unique brain imaging device.

Potential projects include:

  1. Testing of a stress coping smartphone app on heart rate and other measures when faced with real-world stress
  2. Novel techniques for imaging the human brain using a wearable PET scanner

  

Candice Brown, PhD 
Assistant Professor of Neurobiology & Anatomy

Our laboratory uses a combination of molecular, cellular, biochemical, and behavioral approaches to study the effects of acute systemic inflammation, e.g. sepsis, septic shock, or ischemic stroke, on brain inflammatory pathways that affect blood-brain barrier (BBB) integrity. We integrate this research with the study of sex differences in order in to better understand how male brains and female brains respond differently to acute systemic inflammation. To carry out our research, we employ a combination of in vivo mouse models of experimental sepsis, in vitro cell and tissue culture models that mimic sepsis, and recruit sepsis patients in collaboration with the Department of Emergency Medicine. Severe inflammation and infection are typically associated with a loss of blood-brain barrier integrity and long-term cognitive dysfunction in up to 70% of sepsis patients; however, the molecular mechanisms that cause these changes are unclear. The goal of our research is to: 1) elucidate the molecular mechanisms employed by BMECs to suppress pro-inflammatory pathways and support BBB integrity; and 2) identify the short-term and long-term repercussions of BBB dysfunction on cognition, mood, and sensorimotor behaviors. Techniques we use include small animal surgery and handling: mouse models of experimental sepsis or ovariectomy; mouse behavioral testing paradigms for cognition, motor function, and mood behaviors; data analysis and biostatistics for proteomics and metabolomics data sets; cardiac perfusion, tissue dissection (including brain and specific brain regions), brain sectioning; immunocytochemistry and immunohistochemistry. West Virginia leads the nation in the prevalence of cardiovascular disease, diabetes, and obesity. These disorders increase the risk of acquiring infections that lead to sepsis. Since sepsis is a leading cause of short-term and long-term disability, former sepsis patients often exhibit cognitive impairment, motor dysfunction, and an increased susceptibility for developing neurodegenerative disorders. Understanding the molecular mechanisms through which sepsis disrupts BBB integrity will translate into the development of potential therapeutics as well as changes in current clinical practice to limit subsequent neurological dysfunction and disability in sepsis patients.

Potential projects include:

  1. Determine the interaction between sepsis severity and biological sex on cognitive, mood, and sensorimotor behaviors in a mouse model of experimental sepsis.
  2. Use proteomics and metabolomics approaches to assess novel brain inflammatory pathways that are activated after sepsis in mouse brain tissue, mouse serum, and human sepsis patient serum samples.

 

Andrew Dacks, PhD 
Assistant Professor of Biology

We study neuromodulation which is the alteration of neuronal response properties and synaptic weights.  Neuromodulation is often used by the nervous system to affect sensory coding to optimize behavior to meet current physiological demands.  Our lab uses molecular techniques, anatomy, physiology and behavior to understand the organizing principles controlling this fundamental feature of the brain. We focus on the effects of serotonin in the olfactory system using the fruit fly, Drosophila melanogaster as our model organism.  We study a pair of serotonergic neurons that provide serotonin to a large proportion of the brain and can be genetically manipulated across animals. We are currently pursuing two major questions; 1) How and under what circumstances are these two serotonergic neurons regulated? 2) How do these two serotonergic neurons affect odor-guided behavior? Techniques we use include calcium imaging, optogenetics, immunocytochemistry, and behavioral assays. Neuromodulation is a ubiquitous feature of the brain and the dysfunction of serotonin in particular is associated with many neurological disorders including bipolar disorder, depression and schizophrenia.  Understanding the mechanistic basis for the regulation of this process and the behavioral consequences of neuromodulation are fundamental for understanding the consequences of when this neuromodulation goes awry.

Potential projects include:

  1. Determine how circadian circuitry regulates serotonergic neurons in the olfactory system
  2. Determine the role of serotonin in regulating olfactory sensitivity.

Kevin Daly, PhD 
Professor of Biology

Our lab studies the basis of sensory neural function using molecular, anatomical, cellular and behavioral approaches. My laboratory has recently described a histaminergic neural circuit, which consists of just two neurons projecting from motor centers controlling olfactory-guided locomotion behavior and modifies primary olfactory processing; to what end remains unclear. Currently we are seeking to determine the functional role of this circuit along with understanding its development and its presence/absence across a broad taxonomic range. The student will be exposed to a variety of techniques including detailed behavior analysis, intracellular and extracellular multiunit electrophysiology, immunohistochemistry, and behavior pharmacology. Corollary discharge circuits provide sensory pathways with critical information about ongoing behaviors from motor pathways. The diversity of corollary discharge circuit architecture and function is extensive and  they have been observed in nearly every sensory domain except olfaction until now. Failure of these circuits forms the physiological basis of sensory hallucinations in schizophrenia and is associated with most of the other major diseases of the brain. The basic research performed during this summer internship will provide insights into healthy and dysfunctional circuit function, which we expect to translate into new approaches for treatment of such diseases.

Potential projects include:

  1. Determine the extent of expression of a corollary discharge circuit that modulates primary olfactory function across different species.
  2. Characterize the functional role of corollary discharge on odor guided behavior.

Steven Kinsey, PhD 
Assistant Professor of Psychology

Our lab focuses on the endogenous cannabinoid (i.e., cannabis-like) system, using models of anxiety, depression, pain, and inflammation to probe drug treatments for a range of ailments, in mice. We recently developed new mouse models of drug withdrawal in mice and are using cannabinoid drugs to challenge withdrawal-induced behaviors, with the goal of developing new drug withdrawal treatments for people. We are also investigating cannabinoid drugs administered alone and in combination with existing pain and anti-inflammatory drugs to reduce neuropathic pain with limited side effects. In addition to basic mouse handling, SURI students in our lab prepare drugs, run multiple behavioral tests generally relating to pain, emotionality, stress, and memory. We also routinely run hormone and cytokine assays (i.e., ELISAs) from tissues and primary tissue cell cultures (e.g., culture white blood cells from spleens), as well as immunohistochemistry. Some of the novel drug treatments our lab has worked on are now being developed for use in people within the next 5 years. Thus, our work has short-term application to help combat pain and addiction in people.

Potential projects include:

  1. Determine the physiological level (e.g., foot, spinal cord, brain?) where cannabinoids block neuropathic pain elicited by peripheral nerve injury.
  2. Measure the efficacy of different methods of cannabinoid receptor activation in reducing opioid withdrawal-related behaviors.

James W. Lewis, PhD 
Associate Professor of Neurobiology & Anatomy

Our lab studies mechanisms of multisensory and hearing perception, and spoken language processing, using either evoked response potential (ERP) methods or 3 Tesla functional magnetic resonance imaging (fMRI). This includes studying aspects of human auditory system function ranging from processing of low-level features of sound (acoustic signal processing principles) to intermediate- and high-level perceptual features of action sounds and speech processing (cognitive processing), which together mediate our sense of recognition of the every day sounds we hear. We primarily use computational approaches and methods for studying brain function, and thus applicants with a solid background in computer sciences, physics, mathematics, or engineering are preferred.

Potential projects include:

  1. Study of CNS and physiological effects of transcutaneous electrical neural stimulation (TENS) as a treatment therapy/therapies. 
  2. fMRI study identifying auditory and multisensory cortical processing networks in neurotypical and autistic populations.
  3. fMRI meta-analysis of audio-visual interaction sites in the human brain, with relation to clinical assessments for autism diagnoses.

Paul Lockman, PhD 
Professor and Chair of Pharmaceutical Sciences

Our lab focuses on the movement of drugs into brain, how they get there, and how to improve it. Currently chemotherapy fails in women with brain metastases that originated from breast cancer. We are attempting to create novel methods to improve how much drug gets to the tumor.  And we are trying to prevent single cancer cells from entering into brain – thus preventing the formation of brain metastases of breast cancer. We perform cell culture, fluorescent and light microscopy, mathematical modelling, small animal surgeries and injections, bioluminescent imaging. Currently women with metastatic breast cancer have few effective treatment options. Chemotherapy rarely reaches effective concentrations, surgery for the most part is palliative to reduce symptoms and radiation has significant side effects. It is the hope of our lab that we will reduce the mortality and morbidity associated with brain metastases of breast cancer.

Potential projects include:

  1. Determine chemotherapeutic drug uptake in brain metastases of breast cancer
  2. Evaluate drug distribution into brain in stroke conditions

  

Xuefang “Sophie” Ren, MD 
Research Assistant Professor of Physiology & Pharmacology

Our lab takes in vitro, in vivo and ex vivo approaches to study stroke mechanisms and therapeutics. We recently identified mitochondria play an important role in BBB opening. We are further to investigate the regulators that enhance mitochondrial function and protect BBB opening in stroke. Techniques we use include experimental stroke animal model, cell culture model, PCR, Laser-scanning confocal microscopy, live-cell imaging, and immunocytochemistry. Stroke is the fourth leading cause of death and the leading cause of disability among Americans today. By all current estimates, more than one million brain attacks will occur per year in the U.S by 2030. Due to the devastating impairments an individual can encounter after suffering a stroke, there is an immediate need for better understanding of the mechanisms to develop effective treatments. Our study will hopefully provide possible therapy with significant potential to improve quality of life for patients suffering from stroke.

Potential projects include:

  1. Determine the role of miR-34a in blood-brain barrier (BBB) opening
  2. Determine the role of mitochondria in BBB opening
  3. Determine the role of miR-34a in stroke

Vincent Setola, PhD 
Assistant Professor of Physiology & Pharmacology 
David Sidervoski, PhD 
Professor and Chair of Physiology & Pharmacology

(joint research topics)

The Setola and Siderovski labs both study the roles of Regulators of G Protein Signaling (RGS proteins) on neurotransmitter signaling. We are particularly interested in RGS proteins that affect processes in the central and peripheral nervous systems.  For example, our recent work with a mouse strain lacking Rgs12 expression indicates that RGS12 deficiency can reduce hyperlocomotion in response to psychoactive drugs like amphetamine but conversely heighten the pain reduction caused by opioid drugs. We are interested in identifying the particular brain regions and neuronal circuitry involved in these behavioral manifestations. In a related project, the Setola laboratory is surveying a panel of candidate genes, including those encoding RGS proteins, in patients who have been diagnosed with Opioid Abuse Disorder -- testing for gene variations that correlate with drug-seeking behavior and relapse from abstinence programs. Senior graduate students Joshua Gross and Shane Kaski will provide day-to-day laboratory supervision; in addition, Ms. Kim Wix is a senior research technician in the Setola lab and will assist the student with all facets of animal handling. 

Potential projects include:

  1. Testing the behavioral responses of RGS12-deficient mice to psychoactive substances and drugs-of-abuse
  2. Testing candidate human genes for variations that correlate with drug-seeking behavior and relapse from abstinence programs

 

George Spirou, PhD 
Professor of Otolaryngology, and Co-Director of the WVU Blanchette Rockefeller Neurosciences Institute

The Spirou Lab studies the formation of cell groups and appropriate synaptic connections among cell groups during early brain development. Important questions that we address are how neurons cluster spatially into functional units, what factors cause the genesis of synaptic contacts, and how competition among neural projections for a target neuron is resolved. A range of techniques are used in these studies, including cutting-edge laser-based imaging, electrophysiological recording of synaptic currents and cell activity, cell and tissue culture, transgenic animals, fluorescence immunocytochemistry and live-cell imaging, and measures of gene expression using microarray analysis and quantitative PCR. By determining mechanisms for synapse formation in the developing brain, new strategies can be tested as potential therapies for neurodegeneration due to disease or injury.

Potential projects include:

  1. Time-lapse imaging of calyx growth and cellular electrical activity in organotypic culture with manipulation of signaling factors that mediate this process.
  2. Immersive 3D virtual reality analysis of structural dynamics during synapse formation.

  

Eric Tucker, PhD 
Associate Professor of Neurobiology & Anatomy

Our lab takes cellular, molecular, and genetic approaches to study development of the cerebral cortex. We recently identified the c-Jun N-terminal kinase (JNK) signaling pathway as a key mediator of cortical interneuron migration in the developing cerebral cortex. We now seek to uncover molecular mechanisms operating up and down stream of JNK signaling to facilitate interneuron migration, in vivo. Techniques we use include mouse developmental genetics and embryology, cellular and molecular biology, tissue culture: primary neuronal cell culture and organotypic slice culture, ex vivo manipulation of gene expression by electroporation, laser-scanning confocal microscopy, live-cell imaging, and immunocytochemistry. Many neurological and neuropsychiatric disorders, including epilepsy, autism, and schizophrenia, are thought to arise during embryonic development and result from deficiencies in cortical interneurons. Unraveling genetic mechanisms underlying development of inhibitory interneurons will hopefully translate into future treatments for these devastating disorders of cortical circuitry.

Potential projects include:

  1. Resolve cellular and molecular mechanisms underlying migration of cortical interneurons.
  2. Determine how genetic disruption of JNK signaling impacts assembly of inhibitory circuitry in the cerebral cortex.

 

Cole Vonder Haar, PhD 
Assistant Professor of Psychology

Our lab utilizes extensive behavioral testing in order to investigate questions regarding neural injury such as traumatic brain injury and stroke. In one line of research, we are exploring the link between depressive-like behaviors and traumatic brain injury. Recent studies have emphasized comorbidities between TBI and the development of psychiatric disease. In another line of research, we are determining the role of microglia in brief ischemic events and how this may increase tolerance to later stroke. A better understanding of these mechanisms could lead to therapeutics benefiting both stroke and TBI victims. Techniques we use include operant behavioral testing, stereotaxic surgery, multiple injury models (controlled cortical impact, CHIMERA, photothrombotic stroke), immunohistochemistry, and ELISA. Brain injury, in the form of stroke and traumatic brain injury, represents a significant health burden in the United States and worldwide. Individuals with brain injuries are vulnerable to a host of psychiatric diseases, including depression, impulse control problems, and addiction. To understand the causal links, improvement of animal behavioral models and better understanding of pathophysiological changes are needed.

Potential projects include:

  1. Characterize motivational deficits after frontal traumatic brain injury in rats.
  2. (2)  Explore the role of microglia in ischemic preconditioning on functional outcomes.

Sergiy Yakovenko, PhD 
Assistant Professor of Exercise Physiology

The focus of our interdisciplinary lab is to study the coordinated action of neural, muscular, and skeletal systems controlling goal-directed and stereotypic movements. The neuro-musculo-skeletal (NMS) system evolved to control mechanical actions, e.g. walking, running, balancing and reaching. Since these and other common behaviors are produced by the integrated action of multiple components of the NMS system, investigating the details of this emergent organization of movement control is a major challenge. Our laboratory addresses this challenge with an interdisciplinary approach that combines multi-electrode recording and stimulation techniques with advanced computational tools in the field of neuromechanics. The understanding of the interactions between neural and mechanical systems will improve our understanding of brain function and its repair with prostheses. Key questions that we are addressing in our laboratory are: What is the pattern of interactions between multiple redundant neuromechanical mechanisms involved in the control of movement? What are the evolutionary constraints of the neuromechanical organization? What mechanisms are responsible for the way we acquire new motor skills? How can we use the hierarchy and redundancy of control pathways to overcome movement deficits due to stroke and spinal cord injury? Primary techniques used in the lab are high-density microelectrode recording and stimulation in the motor cortex (rodents), EMG, motion capture, dynamics with split-belt treadmill instrumented with force plates for biomechanical and control systems analyses of locomotion in humans and lower animals. Stroke is a prevalent trauma in our population with a new stroke happening every 4 min in U.S., and it is the leading cause of long-term disability. The vast majority of strokes results in sensorimotor dysfunctions that can be treated with extensive rehabilitation. Unraveling motor control system mechanisms responsible for the seamless integration between spinal and supraspinal pathways will help to develop implantable and exoskeletal prostheses to restore lost functionality.

Potential projects include:

  1. Neuromusculoskeletal model of locomotion for studies of motor dysfunctions.
  2. Plasticity of motor cortex during asymmetric locomotion