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.

The research goals of the Functional Neurosurgery Laboratory include the development of computational models to understand how brain function is affected by neurological conditions and how this abnormal function might be corrected or minimized by neuromodulation through electrical stimulation. The lab uses data collected from patients during epilepsy monitoring or in the operating room during DBS procedures to construct and calibrate the computational models. The models can be manipulated to explore functional changes and treatment possibilities. The other primary goal of the laboratory is the development of a neuromodulation system that applies stimulation pulses at specific phases of brain oscillatory activity. This technique is being explored in the context of Parkinson's disease as well as memory function, and may lead to less invasive therapeutic treatment system with more effective stimulation.

Complexity in signaling networks is often derived from co-opting one set of molecules for multiple operations. Understanding how cells achieve such sophisticated processing using a finite set of molecules within a confined space--what we call the ""signaling paradox""--is critical to biology and engineering as well as the emerging field of synthetic biology. In the Inoue Lab, we have recently developed a series of chemical-molecular tools that allow for inducible, quick-onset and specific perturbation of various signaling molecules. Using this novel technique in conjunction with fluorescence imaging, microfabricated devices, quantitative analysis and computational modeling, we are dissecting intricate signaling networks. In particular, we investigate positive-feedback mechanisms underlying the initiation of neutrophil chemotaxis (known as symmetry breaking), as well as spatio-temporally compartmentalized signaling of Ras and membrane lipids such as phosphoinositides. In parallel, we also try to understand how cell morphology affects biochemical pathways inside cells. Ultimately, we will generate completely orthogonal machinery in cells to achieve existing, as well as novel, cellular functions. Our synthetic, multidisciplinary approach will elucidate the signaling paradox created by nature.