Our group is interested in a broad array of clinical and translational investigations spanning the evaluation of basic pathophysiology in patients undergoing cardiac procedures, development and evaluation of new therapeutic strategies, and improving patient selection and outcomes following interventional procedures. We are comprised of a core group of faculty and dedicated research nurses as well as fellows, residents, and students. Projects range from investigator-initiated single-center observational studies to industry-sponsored multicenter phase 3 randomized controlled trials. We have established a database of all patients who have undergone TAVR at Johns Hopkins, which is providing the basis for several retrospective analyses and will serve as the foundation for future studies of TAVR. We are also engaged in collaborative projects with other groups from the Department of Medicine and other Departments including Cardiac Surgery, Anesthesiology, Radiology, Psychiatry, and Biomedical Engineering. Members of our group are actively involved with the Johns Hopkins Center for Bioengineering Innovation and Design (CBID) in the development of novel minimally-invasive cardiovascular devices.

The Cardiology Bioengineering Laboratory, located in the Johns Hopkins Hospital, focuses on the applications of advanced imaging techniques for arrhythmia management. The primary limitation of current fluoroscopy-guided techniques for ablation of cardiac arrhythmia is the inability to visualize soft tissues and 3-dimensional anatomic relationships. Implementation of alternative advanced modalities has the potential to improve complex ablation procedures by guiding catheter placement, visualizing abnormal scar tissue, reducing procedural time devoted to mapping, and eliminating patient and operator exposure to radiation. Active projects include • Physiological differences between isolated hearts in ventricular fibrillation and pulseless electrical activity • Successful ablation sites in ischemic ventricular tachycardia in a porcine model and the correlation to magnetic resonance imaging (MRI) • MRI-guided radiofrequency ablation of canine atrial fibrillation, and diagnosis and intervention for arrhythmias • Physiological and metabolic effects of interruptions in chest compressions during cardiopulmonary resuscitation Henry Halperin, MD, is co-director of the Johns Hopkins Imaging Institute of Excellence and a professor of medicine, radiology and biomedical engineering. Menekhem M. Zviman, PhD is the laboratory manager.

Epilepsy affects 1-3% of the population and can have a profound impact on general health, employment and quality of life. Medial temporal lobe epilepsy (MTLE) develops in some patients following head injury or repeated febrile seizures. Those affected may first suffer spontaneous seizures many years after the initial insult, indicating that the neural circuit undergoes a slow pathologic remodeling over the interim. There are currently no methods of preventing the development of MTLE. It is our goal to better understand the process in order to slow, halt, and ultimately reverse it. Our laboratory draws on electrophysiology, molecular biology, and morphology to study the contribution of dysregulated neurogenesis and newborn neuron connectivity to the development of MTLE. We build on basic research in stem cell biology, hippocampal development, and synaptic plasticity. We work closely with colleagues in the Institute for Cell Engineering, Neurology, Neurosurgery, Biomedical Engineering, and Radiology. As physician neuropathologists our grounding is in tissue alterations underlying human neurologic disease; using human iPSC-derived neurons and surgical specimens we focus on the pathophysiological processes as they occur in patients. By understanding changes in cell populations and morphologies that affect the circuit, and identifying pathologic alterations in gene expression that lead to the cell-level abnormalities, we hope to find treatment targets that can prevent the remodeling and break the feedback loop of abnormal activity > circuit change > abnormal activity.

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.