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Schizophrenia, autism and other neurological disorders are caused by a complex interaction between inherited genetic risk and environmental experiences. The overarching goal of the group are to reveal molecular mechanisms of gene by environment interactions related to altered neural development and liability for brain disorders. Our research uses a hybrid of human stem cell models, post-mortem tissue and computational approaches to interrogate the contribution of epigenetic regulation and somatic mosaicism to brain diseases. Our previous work has demonstrated that the human brain exhibits extensive genetic variability between neurons within the same brain, termed "somatic mosaicism" due to mobile DNA elements which mediate large somatic DNA copy number variants. We study environment-responsive mechanisms and consequences for somatic mosaicism and are discovering the landscape of somatic mosaicism in the brain. We also study the epigenetic regulation of cell specification and activity-d...ependent states within the human dorsal lateral prefrontal cortex and striatum. view more
Esther Oh Lab
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.
Dr. Haughey directs a disease-oriented research program that address questions in basic neurobiology, and clinical neurology. The primary research interests of the laboratory are:
1. To identify biomarkers markers for neurodegenerative diseases including HIV-Associated Neurocognitive Disorders, Multiple Sclerosis, and Alzheimer’s disease. In these studies, blood and cerebral spinal fluid samples obtained from ongoing clinical studies are analyzed for metabolic profiles through a variety of biochemical, mass spectrometry and bioinformatic techniques. These biomarkers can then be used in the diagnosis of disease, as prognostic indicators to predict disease trajectory, or as surrogate markers to track the effectiveness of disease modifying interventions.
2. To better understand how the lipid components of neuronal, and glial membranes interact with proteins to regulate signal transduction associated with differentiation, motility, inflammatory signaling, survival, and neuronal excitab...ility.
3. To understand how extracellular vesicles (exosomes) released from brain resident cells regulate neuronal excitability, neural network activity, and peripheral immune responses to central nervous system damage and infections.
4. To develop small molecule therapeutics that regulate lipid metabolism as a neuroprotective and restorative strategy for neurodegenerative conditions. view less
The APL Health Technologies program's functional restoration focus area includes two portfolios with particular relevance in neurology. The first focuses on motor restoration, using teams with expertise in robotics, microsensors, haptics, artificial intelligence and brain-machine interfaces. One set of projects, currently sponsored by Defense Advanced Research Projects Agency (DARPA) and the Henry Jackson Foundation, centers on a bionic arm technology that integrates with bone and muscle in amputee patients, restoring a variety of normal functions to the patient like cooking, folding clothing, hand shaking, and hand gestures. This portfolio explores direct brain control of the bionic limb, through work led by Dr. Nathan Crone of Johns Hopkins Neurology and Dr. Pablo Celnik of Johns Hopkins Physical Medicine and Rehabilitation. Another set of related work aims to restore motor function by better understanding and using brain signals through brain-machine interfaces. This work is current...ly funded by the National Science Foundation and industry partners. Also in the functional restoration focus area is the vision restoration portfolio. In a partnership with Second Sight and the Mann Fund, the work aims to enhance function of a bionic eye, which couples a retinal implant with a computer vision system to restore vision in blind individuals with retinitis pigmentosa. Current work in the human-machine teaming focus area includes a portfolio that is building artificial intelligence systems that improve radiologic and ophthalmic diagnostics. Another portfolio, currently focused in the surgical setting, enhances the physician's ability to visualize and manipulate the physical world, such as with orthopaedic surgery. view more
Healthy Brain Program
The Brain Health Program is a multidisciplinary team of faculty from the departments of neurology, psychiatry, epidemiology, and radiology lead by Leah Rubin and Jennifer Coughlin. In the hope of revealing new directions for therapies, the group studies molecular biomarkers identified from tissue and brain imaging that are associated with memory problems related to HIV infection, aging, dementia, mental illness and traumatic brain injury. The team seeks to advance policies and practices to optimize brain health in vulnerable populations while destigmatizing these brain disorders.
Current and future projects include research on: the roles of the stress response, glucocorticoids, and inflammation in conditions that affect memory and the related factors that make people protected or or vulnerable to memory decline; new mobile apps that use iPads to improve our detection of memory deficits; clinical trials looking at short-term effects of low dose hydrocortisone and randomized to 28 day...s of treatment; imaging brain injury and repair in NFL players to guide players and the game; and the role of inflammation in memory deterioration in healthy aging, patients with HIV, and other neurodegenerative conditions. view less
The Human Brain Physiology and Stimulation Laboratory studies the mechanisms of motor learning and develops interventions to modulate motor function in humans. The goal is to understand how the central nervous system controls and learns to perform motor actions in healthy individuals and in patients with neurological diseases such as stroke. Using this knowledge, we aim to develop strategies to enhance motor function in neurological patients.
To accomplish these interests, we use different forms of non-invasive brain stimulation techniques, such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), as well as functional MRI and behavioral tasks.
The Institute for Computational Medicine's mission is to develop quantitative approaches for understanding the mechanisms, diagnosis and treatment of human disease through biological systems modeling, computational anatomy, and bioinformatics. Our disease focus areas include breast cancer, brain disease and heart disease.
The institute builds on groundbreaking research at both the Johns Hopkins University Whiting School of Engineering and the School of Medicine.
Currently supported research includes pathophysiology of fetal brain development with intrauterine insults, ultrasound and bio- markers of fetal well-being and biomarkers for fetal disease stratification and response to treatment (such as magnesium sulfate administration or head cooling as in cases of neuroinflammation).
James Barrow Laboratory
The James Barrow Laboratory studies drug discovery at the Lieber Institute. He leads research related to medicinal chemistry, biology, and drug metabolism, with the goal of validating novel mechanisms and advancing treatments for disorders of brain development.
James Knierim Laboratory
Research in the James Knierim Laboratory attempts to understand the flow of information through the hippocampal formation and the computations performed by the various subfields of the hippocampus and its inputs from the entorhinal cortex. To address these issues, we use multi-electrode arrays to record the extracellular action potentials from scores of well-isolated hippocampal neurons in freely moving rats.
These neurons, or "place cells," are selectively active when the rat occupies restricted locations in its environment and help to form a cognitive map of the environment. The animal uses this map to navigate efficiently in its environment and to learn and remember important locations. These cells are thought to play a major role in the formation of episodic (autobiographical) memories. Place cells thus constitute a tremendous opportunity to investigate the mechanisms by which the brain transforms sensory input into an internal, cognitive representation of the world and then use...s this representation as the framework that organizes and stores memories of past events. view more