The Esther Oh Lab is interested in developing biological markers for pre-clinical stages of Alzheimer's disease (AD). Our current research involves using transgenic models of AD to develop peripheral injections of monoclonal antibodies against amyloid-beta as a tool to detect a level of amyloid-beta that would be correlative to the amyloid-beta level in the brain.

Research in the Bakker Memory Laboratory is focused on understanding the mechanisms and brain networks underlying human cognition with a specific focus on the mechanisms underlying learning and memory and the changes in memory that occur with aging and disease. We use a variety of techniques including neuropsychological assessments, experimental behavioral assessments and particularly advanced neuroimaging methods to study these questions in young and older adults and patients with mild cognitive impairment, Alzheimer’s disease, Parkinson’s disease and epilepsy. Through our collaborations with investigators in both basic science and clinical departments, including the departments of Psychiatry and Behavioral Sciences, Psychological and Brain Sciences, Neurology and Public Health, our research also focuses on brain systems involved in spatial navigation and decision-making as well as cognitive impairment in neuropsychiatric conditions such as schizophrenia, eating disorders, obsessive-compulsive disorders, depression and anxiety.

The mission of the laboratory of vestibular neurophysiology is to advance the understanding of how the body perceives head motion and maintains balance - a complex and vital function of everyday life. Although much is known about the vestibular part of the inner ear, key aspects of how the vestibular receptors perceive, process and report essential information are still mysterious. Increasing our understanding of this process will have tremendous impact on quality of life of patients with vestibular disorders, who often suffer terrible discomfort from dizziness and vertigo. The laboratory group's basic science research focuses on the vestibulo-ocular reflexes - the reflexes that move the eyes in response to motions of the head. They do this by studying the vestibular sensors and nerve cells that provide input to the reflexes; by studying eye movements in humans and animals with different vestibular disorders, by studying effects of electrical stimulation of vestibular sensors, and by using mathematical models to describe these reflexes. Researchers are particularly interested in abnormalities of the brain's inability to compensate for vestibular disorders.

Vascular research led by Rafael Tamargo, M.D., the Walter E. Dandy Professor of Neurosurgery, explores treatment of aneurysms, arteriovenous malformations, cavernous malformations, and arteriovenous fistulas of the brain and spinal cord. Basic science research has focused on endothelial cell-leukocyte interactions (inflammation) after subarachnoid hemorrhage and identifying drugs that might inhibit this inflammatory response as well as the narrowing of blood vessels.

The Veit Stuphorn Laboratory studies the neurophysiological mechanisms that underlie decision making and self-control. We record the activity of single neurons in awake animals that are engaged in decision-making processes. This allows us to identify the types of signals that neurons in specific parts of the brain represent and the computations they carry out. We also study human subjects in the same tasks with the help of fMRI. These parallel experiments provide comparative information about decision processes in human and non-human primates.

The Raman laboratory is within the Division of Cancer Imaging Research in the Department of Radiology and Radiological Science. The focus of the laboratory is bench-to-bed side cancer research. We integrate molecular and cellular biology, developmental biology, cancer biology, molecular imaging techniques to study cancer formation and progression. Many of the projects in the lab investigate dysregulated genes in cancer and the translatability of this information to a clinical setting. One such project is to functionally decipher the role of a RNA helicase gene, DDX3, in the biogenesis of multiple cancer types such as breast, lung, brain, sarcoma, colorectal and prostate. Additionally, using a rational drug design approach, a small molecule inhibitor of DDX3 (RK-33) was synthesized and its potential for clinical translation is being investigated.

Research in the Vestibular NeuroEngineering Lab (VNEL) focuses on restoring inner ear function through “bionic” electrical stimulation, inner ear gene therapy, and enhancing the central nervous system’s ability to learn ways to use sensory input from a damaged inner ear. VNEL research involves basic and applied neurophysiology, biomedical engineering, clinical investigation and population-based epidemiologic studies. We employ techniques including single-unit electrophysiologic recording; histologic examination; 3-D video-oculography and magnetic scleral search coil measurements of eye movements; microCT; micro MRI; and finite element analysis. Our research subjects include computer models, circuits, animals and humans. For more information about VNEL, click here. VNEL is currently recruiting subjects for two first-in-human clinical trials: 1) The MVI Multichannel Vestibular Implant Trial involves implantation of a “bionic” inner ear stimulator intended to partially restore sensation of head movement. Without that sensation, the brain’s image- and posture-stabilizing reflexes fail, so affected individuals suffer difficulty with blurry vision, unsteady walking, chronic dizziness, mental fogginess and a high risk of falling. Based on designs developed and tested successfully in animals over the past the past 15 years at VNEL, the system used in this trial is very similar to a cochlear implant (in fact, future versions could include cochlear electrodes for use in patients who also have hearing loss). Instead of a microphone and cochlear electrodes, it uses gyroscopes to sense head movement, and its electrodes are implanted in the vestibular labyrinth. For more information on the MVI trial, click here. 2) The CGF166 Inner Ear Gene Therapy Trial involves inner ear injection of a genetically engineered DNA sequence intended to restore hearing and balance sensation by creating new sensory cells (called “hair cells”). Performed at VNEL with the support of Novartis and through a collaboration with the University of Kansas and Columbia University, this is the world’s first trial of inner ear gene therapy in human subjects. Individuals with severe or profound hearing loss in both ears are invited to participate. For more information on the CGF166 trial, click here.

In the Lee Martin Laboratory, we are testing the hypothesis that selective vulnerability--the phenomenon in which only certain groups of neurons degenerate in adult onset neurological disorders like amyotrophic lateral sclerosis and Alzheimer's disease--is dictated by brain regional connectivity, mitochondrial function and oxidative stress. We believe it is mediated by excitotoxic cell death resulting from abnormalities in excitatory glutamatergic signal transduction pathways, including glutamate transporters and glutamate receptors as well as their downstream intracellular signaling molecules. We are also investigating the contribution of neuronal/glial apoptosis and necrosis as cell death pathways in animal (including transgenic mice) models of acute and progressive neurodegeneration. We use a variety of anatomical and molecular neurobiological approaches, including neuronal tract-tracing techniques, immunocytochemistry, immunoblotting, antipeptide antibody production, transmission electron microscopy and DNA analysis to determine the precise regional and cellular vulnerabilities and the synaptic and molecular mechanisms that result in selective neuronal degeneration.

The neuroimaging and Modulation Laboratory (NIMLAB) investigates neural correlates of cognition and behavior using neuroimaging methods such as functional magnetic resonance imaging (fMRI) and neuromodulation techniques such as transcranial magnetic stimulation (TMS). We are looking in depth at the contributions of the cerebellum and cerebro-cerebellar circuits to cognition; the effects of chronic heavy alcohol consumption on cognition and brain activation underlying cognitive function; how aging in humans affects neural systems that are important for associative learning and stimulus awareness; and the integration of transcranial magnetic stimulation with functional MRI.

In our laboratory we study the brain mechanisms of eye movements and spatial orientation. -How magnetic stimulation through transcranial devices affects cortical brain regions -Neural mechanisms underlying balance, spatial orientation and eye movement -Mathematical models that describe the function of ocular motor systems and perception of spatial orientation -Short- and long-term adaptive processes underlying compensation for disease and functional recovery in patients with ocular motor, vestibular and perceptual dysfunction Developing and testing novel diagnostic tools, treatments, and rehabilitative strategies for patients with ocular motor, vestibular and spatial dysfunction