The Kristina Nielsen Laboratory investigates neural circuits in the visual cortex that are responsible for encoding objects to understand how the visual system performs object recognition. We aim to reveal the fine-scale organization of neural circuits, with an emphasis on higher-level visual areas. We use two-photon microscopy to perform high-resolution functional imaging of visual areas in the non-human primate. We also investigate how the function of higher visual areas changes over the course of brain development in ferrets, by measuring the activity of single neurons in these areas, as well as determining the animal's visual capabilities at various developmental stages. In both types of investigations, we also rely on detailed anatomical techniques to precisely observe how the function of neuronal circuits is related to their structure.

The Shanthini Sockanathan Laboratory uses the developing spinal cord as our major paradigm to define the mechanisms that maintain an undifferentiated progenitor state and the molecular pathways that trigger their differentiation into neurons and glia. The major focus of the lab is the study of a new family of six-transmembrane proteins (6-TM GDEs) that play key roles in regulating neuronal and glial differentiation in the spinal cord. We recently discovered that the 6-TM GDEs release GPI-anchored proteins from the cell surface through cleavage of the GPI-anchor. This discovery identifies 6-TM GDEs as the first vertebrate membrane bound GPI-cleaving enzymes that work at the cell surface to regulate GPI-anchored protein function. Current work in the lab involves defining how the 6-TM GDEs regulate cellular signaling events that control neuronal and glial differentiation and function, with a major focus on how GDE dysfunction relates to the onset and progression of disease. To solve these questions, we use an integrated approach that includes in vivo models, imaging, molecular biology, biochemistry, developmental biology, genetics and behavior.

The Paul Worley Lab examines the molecular basis of learning and memory. In particular, we cloned a set of immediate early genes (IEGs) that are rapidly transcribed in neurons involved in information processing, and that are essential for long term memory. IEG proteins can directly modify synapses and provide insight into cellular mechanisms that support synapse-specific plasticity.

The Christopher Potter Lab functions at an intersection between systems and cellular neuroscience. We are interested in how neurons and circuits function in the brain to achieve a common goal (olfaction), but we also develop, utilize and build tools (molecular and genetic) that allow us to directly alter neuronal functions in a living organism. The specific focus of my laboratory is to understand how the insect brain receives, interprets, and responds to odors. Insects rely on their sense of smell for all major life choices, from foraging to mating, from choosing where to lay eggs to avoiding predators and dangers. We are interested in understanding at the neuronal level how odors regulate these behaviors. Our long-term aim is to apply this knowledge to better control insects that pose a threat to human health. Our general approach towards achieving this goal is to develop and employ new genetic methods that enable unprecedented control over neural circuits in both the model organism Drosophila melanogaster and human malaria vector Anopheles gambiae.

Research in the Raymond Koehler Lab explores cerebrovascular physiology and cerebral ischemic injury caused by stroke and cardiac arrest, using protein analysis, immunohistochemistry and histology. We also study ischemic preconditioning, neonatal hypoxic-ischemic encephalopathy and the mechanisms of abnormal cerebrovascular reactivity after ischemia. We 're examining ways to improve tissue oxygenation and seek to better understand the mechanisms that connect an increase in cerebral blood flow to neuronal activity.

The Wolfgang Laboratory is interested in understanding the metabolic properties of neurons and glia at a mechanistic level in situ. Some of the most interesting, enigmatic and understudied cells in metabolic biochemistry are those of the nervous system. Defects in these pathways can lead to devastating neurological disease. Conversely, altering the metabolic properties of the nervous system can have surprisingly beneficial effects on the progression of some diseases. However, the mechanisms of these interactions are largely unknown. We use biochemical and molecular genetic techniques to study the molecular mechanisms that the nervous system uses to sense and respond to metabolic cues. We seek to understand the neurometabolic regulation of behavior and physiology in obesity, diabetes and neurological disease. Current areas of study include deconstructing neurometabolic pathways to understand the biochemistry of the nervous system and how these metabolic pathways impact animal behavior and physiology, metabolic heterogeneity and the evolution of metabolic adaptation.

Our laboratory conducts basic and translational research aimed at better understanding the pathogenesis of multiple sclerosis (MS) and the role of the immune system in CNS disease, particularly the processes that drive progressive disability such as neurodegeneration and remyelination failure. We currently have three parallel research programs: 1. Metabolism as a modulator of MS: We are studying how basic metabolic pathways regulate the immune system and how these pathways might be exploited to protect neurons and myelin-forming oligodendrocytes from injury. 2. Identifying pathways by which nitric oxide (NO) and other free radicals cause neuronal and axonal damage. Our lab is identifying specific signaling pathways initiated by NO and other free radicals that can be targeted by drugs to produce neuroprotection. 3. Modulating the innate immune system in MS: In collaboration with others at Johns Hopkins, we are studying ways to enhance the reparative functions of microglia while preventing maladaptive responses. This work has identified bryostatin-1 as a potential drug that may be re-purposed for this task.

Dr. Fridman's research group invents and develops bioelectronics for Neuroengineering and Medical Instrumentation applications. We develop innovative medical technology and we also conduct the necessary biological studies to understand how the technology could be effective and safe for people. Our lab is currently focused on developing the ""Safe Direct Current Stimulation"" technology, or SDCS. Unlike the currently available commercial neural prosthetic devices, such as cochlear implants, pacemakers, or Parkinson's deep brain stimulators that can only excite neurons, SDCS can excite, inhibit, and even sensitize them to input. This new technology opens a door to a wide range of applications that we are currently exploring along with device development: e.g. peripheral nerve stimulation for suppressing neuropathic pain, vestibular nerve stimulation to correct balance disorders, vagal nerve stimulation to suppress an asthma attack, and a host of other neuroprosthetic applications. Medical Instrumentation MouthLab is a ""tricorder"" device that we invented here in the Machine Biointerface Lab. The device currently obtains all vital signs within 60s: Pulse rate, breathing rate, temperature, blood pressure, blood oxygen saturation, electrocardiogram, and FEV1 (lung function) measurement. Because the device is in the mouth, it has access to saliva and to breath and we are focused now on expanding its capability to obtaining measures of dehydration and biomarkers that could be indicative of a wide range of internal disorders ranging from stress to kidney failure and even lung cancer.

The research conducted in the Mumm Lab (Dept. of Ophthalmology, Wilmer Eye Institute) is focused on understanding how neural circuits are formed, how they function, and how they can be regenerated, to develop new therapies for retinal regeneration. Toward that end, we investigate the development, function, and regeneration of disease-relevant neurons and neural circuits responsible for vision. An emphasis is placed on translating what can be learned in regenerative model systems to develop novel therapies for stimulating dormant regenerative capacities in humans, Therefore, we apply what we learn from a naturally regenerative species, the zebrafish, toward the development of novel therapies for restoring visual function to patients. We place an emphasis on unique perspectives zebrafish afford to biological studies, such as in vivo time-lapse imaging of cellular behaviors and cell-cell interactions, and high-throughput chemical and genetic screening. We have pioneered several technologies to support this work including multicolor imaging of neural circuit formation, a selective cell ablation methodology, and a quantitative high-throughput phenotypic screening platform. Together, these approaches are providing novel insights into how the degeneration and regeneration of discrete retinal cell types is controlled.

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.