2016 Participating Mentors
Aric Agmon, PhD:
Professor, Neurobiology & Anatomy
Our lab uses in-vitro and in-vivo electrophysiology to study the synaptic connectivity of the cerebral cortex in the mouse, with emphasis on thalamocortical connections with inhibitory cortical interneurons. We use genetically modified mice to label specific components of the pathway with fluorescent proteins or to express designer channels, which allow us to stimulate the pathway with light (“optogenetics”) or with drugs (“chemogenetics”). The cerebral cortex is – by some accounts - the most complex piece of matter in the universe, but we believe that it can be understood by deciphering its “wiring diagram” – the pattern of synaptic connectivity between the different cell types that it comprises. We attempt to “crack the cortical code” by (1) identifying these different cell type, and (2) determining how they “talk” to each other. Depending on the student and the project, the student may learn to (1) track freely behaving mice using computer-assisted video tracking software, (2) train mice in an object-discrimination task, (3) use viral injections to express genetically-encoded constructs in specific neuronal populations, (4) prepare live thalamocortical slices for time-lapse confocal imaging, (4) process mouse brain tissue for near super-resolution confocal imaging. The cerebral cortex is where all sensory information gets processed and where decisions about appropriate motor actions are made. In humans, the cerebral cortex is also where our uniquely human functions such as thoughts, creativity and language are believed to arise. Any disruption to cortical structure or function, e.g. as a result of genetic malformation, trauma, stroke, or neurodegeneration, can be devastating to the afflicted individuals and their families. Understanding the basic synaptic circuitry underlying cortical function can therefore help researchers develop interventions that may prevent, ameliorate and even repair the damaged cortex, or develop neural prosthetics that will take over the compromised functions.
- Perform live imaging of developing thalamocortical axons in brain slices from embryonic mice.
- Use optogenetics or chemogenetics to silence specific populations of neurons in freely behaving mice.
- Use novel activity-dependent fluorescent markers to map the connections between thalamus and cortex in behaving mice.
Julie Brefczynski-Lewis, PhD:
Research Assistant Professor, 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.
- Testing of a stress coping Smartphone app on heart rate and other measures when faced with real-world stress.
- Novel techniques for imaging the human brain using a wearable PET scanner.
Candice Brown, PhD:
Assistant Professor, Neurobiology & Anatomy
Our laboratory uses a combination of molecular, cellular, biochemical, and behavioral approaches to study the effects of acute systemic inflammation, e.g. infections that result in sepsis and septic shock, on brain microvascular endothelial cell (BMEC) pro-inflammatory pathways and on 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 and in vitro cell and tissue culture models that mimic sepsis. The blood-brain barrier (BBB) is a selective chemical and structural interface that is composed primarily of brain microvascular endothelial cells (BMECs). Inflammation and infection are typically associated with a loss of BBB integrity and an increase in BBB permeability; 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. Students will have the opportunity to learn the following techniques: Small animal surgery: mouse model of experimental sepsis – cecal ligation and puncture, ovariectomy; Mouse behavioral testing paradigms for cognition, motor function, and anxiety/depression-like behaviors; Cardiac perfusion, tissue dissection (including brain and specific brain regions), brain sectioning; Cell culture: brain endothelial cells and astrocytes; Immunocytochemistry and immunohistochemistry; Brightfield, fluorescence, and confocal microscopy; High-throughput image analysis.
- Determine the short-term and long-term effects of acute systemic inflammation (e.g. sepsis) on cognition, sensorimotor behaviors, and mood in a mouse model of experimental sepsis.
- Determine spatial and temporal differences in blood-brain barrier integrity and permeability due to acute systemic inflammation in a mouse model of experimental sepsis.
Andrew Dacks, PhD:
Assistant Professor, 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 have two primary questions. 1) How and under what circumstances does the nervous system regulate neuromodulation? 2) How does the expression of individual neuromodulatory receptors by specific populations of neurons result in the overall effects of neuromodulation on network activity and animal behavior? Neuromodulation is a ubiquitous feature of the brain and as such it’s dysfunction is associated with many neurological disorders including bipolar disorder, depression and schizophrenia. Understanding the mechanistic basis for the regulation of this process and the consequences of neuromodulatory receptor expression are fundamental for understanding the consequences of when this neuromodulation goes awry. Students will have the opportunity to learn: Calcium imaging, optogenetics, immunocytochemistry, behavioral assays.
- Determine the mechanisms of circadian regulation of serotonergic modulation of olfactory processing.
- Determine the contribution of individual receptors to the effects of serotonin on olfactory processing.
Kevin Daly, PhD:
Woodburn Professor, 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.
- Determine the extent of expression of a corollary discharge circuit that modulates primary olfactory function across different species.
- Characterize the functional role of corollary discharge on odor guided behavior.
Valeriya Gritsenko, PhD:
Assistant Professor, Human Performance - Physical Therapy
Our lab conducts experimental and computational studies of the neural control of movement in both healthy people and stroke patients. We are trying to understand how the neural motor command to muscles is produced from both sensory signals and internal predictive signals. Primary techniques used in the lab are 3D motion capture to record movement of body segments, electromyography to record muscle activity, transcranial magnetic stimulation to activate the brain, electrical stimulation to activate peripheral nerves, and virtual reality to design experimental conditions. We also create biomechanical models of human limbs and run dynamic simulations to test different hypotheses about the neural control mechanisms. Structural MRI and DTI with 3T scanner. Our studies are aimed at quantifying and automating clinical movement assessment and translating research findings into clinical practice. We are using these approaches to develop home-based rehabilitation techniques, including telemedicine and computer games for physical therapy, to treat movement impairment due to stroke, Parkinson’s disease, or spinal cord injury.
- Muscle and neural synergies during reaching with varying dynamic loads in healthy humans and people with stroke.
- MRI of arm anatomy for dynamic musculoskeletal modeling in MATLAB and OpenSim.
Steven Kinsey, PhD:
Assistant Professor, Psychology
The Kinsey lab studies the cannabinoid system. Although it is not well known, because the receptors were just recently discovered, the cannabinoid system is responsible for the effects cannabis has in the brain and other parts of the body. This summer, our lab will work on two major projects involving cannabinoids, using mice. The first has to do with developing new treatments for rheumatoid arthritis. The goal is to tap into the anti-inflammatory effects of cannabinoids while avoiding the psychogenic "high". The second project will investigate new mouse models of THC withdrawal. Although not as big a problem in our region as opioids, cannabis is an addictive drug that can be difficult for many people to quit, and the goal of these studies is to develop pharmacological treatments for cannabis withdrawal for use in people. A SURI in our lab would have the opportunity to work on one or both projects and will gain experience using behavioral, immunological, and pharmacological techniques.
- Develop potential new treatments for rheumatoid arthritis using the anti-inflammatory effects of cannabinoids while avoiding the psychogenic "high."
- Investigate new mouse models of THC withdrawal, which would help in the development of pharmacological treatments for cannabis withdrawal.
Saravanan Kolandaivelu, PhD:
Research Assistant Professor, WVU Eye Institute
Our goal is to decipher the importance of post-translational lipid protein modification in function and survival of retinal neurons. In particular, our main objective is to study the role of dynamic post-translational lipid modification “palmitoylation” in protein assembly, stability and sorting to various compartments in the photoreceptor cells. The role of palmitoylation in retina is poorly understood mainly due to lack of our knowledge about protein substrates that are modified by palmitoyl group and enzymes that are involved in this modification. We identified several palmitoylated proteins in retinal neurons. Currently, we are working to uncover the molecular mechanism behind palmitoylation in photoreceptor function and survival using animal models and in-vitro tissue culture expression studies. Students will have the opportunity to learn: Generation and characterization of animal models using Crisp/Cas9, various cellular and molecular biology techniques includes gene cloning, protein expression, immunoblotting, immunocytochemistry, laser-scanning confocal microscopy, mammalian tissue cultures studies, and electroretinogram (ERG). Our research will significantly advance for understanding and how the photoreceptor proteins are trafficked and sorted to various cellular compartments and the role of lipid modification in photoreceptor neurons survival and function. We strongly believe that these studies have the strong potential to reveal an important “missing link” between protein lipid modification and retinal function which will significantly advance the knowledge in the field of photoreceptor cell biology.
- Mechanism behind human blinding disease.
- Post translational lipid modification and blinding diseases.
James W. Lewis, PhD:
Associate Professor, 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.
- ERP studies examining how vocalizations produced by the human vocal tract are differentially processed in the brain, with application to intelligent hearing aid design.
- FMRI study identifying auditory and multisensory cortical processing networks in both neurotypical and autistic populations.
Paul Lockman, PhD:
Professor & Chair, 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. Students will have the opportunity to learn: cell culture, fluorescent and light microscopy, mathematical modelling, small animal surgeries and injections, and 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.
- Determine chemotherapeutic drug uptake in brain metastases of breast cancer .
- Evaluate drug distribution into brain in stroke conditions .
George Spirou, PhD:
Professor, Otolaryngology; Director, Centers for Neuroscience
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.
- 1Time-lapse imaging of calyx growth and cellular electrical activity in organotypic culture with manipulation of signaling factors that mediate this process.
- Immersive 3D virtual reality analysis of structural dynamics during synapse formation.
Eric Tucker, PhD:
Assistant Professor, 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. 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. A student would have the opportunity to learn: 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, Immunocytochemistry.
- Resolve cellular and molecular mechanisms underlying migration of cortical interneurons.
- Determine how genetic disruption of JNK signaling impacts assembly of inhibitory circuitry in the cerebral cortex.
Sergiy Yakovenko, PhD:
Assistant Professor, Human Performance - Exercise Physiology
Neural Engineering Laboratory: 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. Questions we are trying to answer: 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.
- Neuromusculoskeletal model of locomotion for studies of motor dysfunctions.
- Plasticity of motor cortex during asymmetric locomotion.