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Researchers in the Adam Sapirstein Lab focus on the roles played by phospholipases A2 and their lipid metabolites in brain injury. Using in vivo and in vitro models of stroke and excitotoxicity, the team is examining the roles of the cytosolic, Group V, and Group X PLA2s as well as the function of PLA2s in cerebrovascular regulation. Investigators have discovered that cPLA2 is necessary for the early electrophysiologic changes that happen in hippocampal CA1 neurons after exposure to N-methyl-d-aspartate (NMDA). This finding has critical ramifications in terms of the possible uses of selective cPLA2 inhibitors after acute neurologic injuries.
The Aliaksei Pustavoitau Lab conducts research on models and mechanisms of impaired consciousness in patients who have suffered acute brain injury. Examples of our work include a study on the mechanisms of neurologic failure in critical illness and another on the use of intensivist-driven ultrasound at the PICU bedside. We also have a longstanding interest in patient safety and quality of care in the ICU setting.
Principal Investigator
Department
The Amit Pahwa Lab conducts research on a variety of topics within internal medicine. Our most recent studies have explored misanalysis of urinalysis results, urinary fractional excretion indices in the evaluation of acute kidney injury and nocturnal enuresis as a risk factor for falls in older women. We also investigate cancer diagnostics and treatments. In this area, our recent research has included studying cutaneous shave biopsies for diagnosing primary colonic adenocarcinoma as well as growth inhibition and apoptosis in human brain tumor cell lines using selenium.
The overall goal of the Auditory Brainstem Library is to understand how abnormal auditory input from the ear affects the brainstem, and how the brain in turn affects activity in the ear through efferent feedback loops. Our emphasis is on understanding the effects of different forms of acquired hearing loss (genetic, conductive, noise-induced, age-related, traumatic brain injury-related) and environmental noise. We are particularly interested in plastic changes in the brain that compensate for some aspects of altered auditory input, and how those changes relate to central auditory processing deficits, tinnitus, and hyperacusis. Understanding these changes will help refine therapeutic strategies and identify new targets for treatment. We collaborate with other labs in the Depts. of Otolaryngology, Neuroscience, Neuropathology, the Wilmer Eye Institute, and the Applied Physics Laboratory at Johns Hopkins, in addition to labs outside the university to increase the impact and clinical relev...ance of our research. view more
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, obsessiv...e-compulsive disorders, depression and anxiety. view more
Research in the Biophotonics Imaging Technologies (BIT) Laboratory focuses on developing optical imaging and nano-biophotonics technology to reduce the random sampling errors in clinical diagnosis, improve early disease detection and guidance of biopsy and interventions, and improve targeted therapy and monitoring treatment outcomes. The imaging technologies feature nondestructiveness, unique functional and molecular specificity, and multi-scale resolution (from organ, to architectural morphology, cellular, subcellular and molecular level). The nano-biophotonics technologies emphasize heavily on biocompatibility, multi-function integration and fast track clinical translation. These imaging and nano-biophotonics technologies can also be potentially powerful tools for basic research such as for drug screening, nondestructive assessment of engineered biomaterials in vitro and in vivo, and for studying brain functions on awake animals under normal or controlled social conditions.
The goal of the Johns Hopkins Brain Cancer Biology and Therapy Laboratory is to locate the genetic and genomic changes that lead to brain cancer. These molecular changes are evaluated for their potential as therapeutic targets and are often mutated genes, or genes that are over-expressed during the development of a brain cancer. The brain cancers that the Riggins Laboratory studies are medulloblastomas and glioblastomas. Medulloblastomas are the most common malignant brain tumor for children and glioblastomas are the most common malignant brain tumor for adults. Both tumors are difficult to treat, and new therapies are urgently needed for these cancers. Our laboratory uses large-scale genomic approaches to locate and analyze the genes that are mutated during brain cancer development. The technologies we now employ are capable of searching nearly all of a cancer genome for molecular alterations that can lead to cancer. The new molecular targets for cancer therapy are first located by l...arge scale gene expression analysis, whole-genome scans for altered gene copy number and high throughput sequence analysis of cancer genomes. The alterations we find are then studied in-depth to determine how they contribute to the development of cancer, whether it is promoting tumor growth, enhancing the ability for the cancer to invade into normal tissue, or preventing the various fail-safe mechanisms programmed into our cells. view more
The Brain Science Institute (BSi) brings together both basic and clinical neuroscientists from across the Johns Hopkins campuses. The BSi represents one of the largest and most diverse groups in the university. The BSi's mission is to solve fundamental questions about brain development and function and to use these insights to understand the mechanisms of brain disease. This new knowledge will provide the catalyst for the facilitation and development of effective therapies. The goals of our research are to foster new programs in basic neuroscience discovery; initiate a translational research program that will develop new treatments for brain-based diseases; and encourage collaboration, interdisciplinary teams, and new thinking that will have a global influence on research and treatment of the nervous system.
The Brown Lab is focused on the function of the cerebral cortex in the brain, which underlies our ability to interact with our environment through sensory perception and voluntary movement. Our research takes a bottom-up approach to understanding how the circuits of this massively interconnected network of neurons are functionally organized, and how dysfunction in these circuits contributes to neurodegenerative diseases like amyotrophic lateral sclerosis and neuropsychiatric disorders, including autism and schizophrenia. By combining electrophysiological and optogenetic approaches with anatomical and genetic techniques for identifying cell populations and pathways, the Brown Lab is defining the synaptic interactions among different classes of cortical neurons and determining how long-range and local inputs are integrated within cortical circuits. In amyotrophic lateral sclerosis, corticospinal and spinal motor neurons progressively degenerate. The Brown Lab is examining how abnormal ...activity within cortical circuits contributes to the selective degeneration of corticospinal motor neurons in an effort to identify new mechanisms for treating this disease. Abnormalities in the organization of cortical circuits and synapses have been identified in genetic and anatomical studies of neuropsychiatric disease. We are interested in the impact these abnormalities have on cortical processing and their contribution to the disordered cognition typical of autism and schizophrenia. view more
Researchers in the C. David Mintz Lab seek to better understand the specific methods by which anesthesia can impair a patient’s brain development. Recent studies have investigated the ways in which anesthetics interfere with axon guidance in developing mouse neocortical neurons via a GABAA receptor mechanism, as well as the method by which anesthetics interfere with the polarization of developing cortical neurons.
Principal Investigator
Department
Dr. Colantuoni and his colleagues explore human brain development and molecular mechanisms that give rise to risk for complex brain disease. His team uses genomic technologies to examine human brain tissue as well as stem models and vast public data resources.
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 D...rosophila melanogaster and human malaria vector Anopheles gambiae. view more
Our laboratory investigates the neural bases of sound processing in the human brain. We combine electrophysiology recordings (intracranial, scalp), behavioral paradigms, and statistical modeling methods to study the cortical dynamics of normal and impaired auditory perception. We are interested in measuring and modeling variability in spatiotemporal cortical response patterns as a function of individual listening abilities and acoustic sound properties. Current studies are investigating the role of high-frequency (>30 Hz) neural oscillations in human auditory perception.
The Cochlear Neurotransmission Group studies the generation and propagation of neural signals in the inner ear. Our laboratories use biophysical, electrophysiological, molecular biological and histological methods to determine fundamental molecular mechanisms by which neurotransmitters are released from primary sensory cells ('hair cells') to excite second order neurons carrying information to the brain. We apply these same techniques to study inhibitory feedback produced by brain neurons that project to and regulate the sensitivity of the cochlea.
The Cohen Lab studies neural circuits underlying reward, mood and decision making. We seek to understand how neural circuits control fundamental mammalian behaviors. Many disorders, including depression, schizophrenia, drug addiction and Parkinson's disease, appear to involve dysfunction of monoaminergic signaling. Using cell-type-specific tools and well-controlled behavioral tasks in mice, we aim to understand the function of monoaminergic circuits in behavior. We hope these basic discoveries will lead to an understanding of the biology of the brain and better treatments for disorders of the brain.
Work in the Courtney Robertson Lab is focused on identifying interventions that could minimize the neurological deficits that can persist after pediatric traumatic brain injury (TBI). One study used a preclinical model to examine potential disruption of mitochondrial function and alterations in cerebral metabolism. It was found that a substantial amount of mitochondrial dysfunction is present in the first six hours after TBI. In addition, we are using nuclear magnetic resonance spectroscopy to evaluate global and regional alterations in brain metabolism after TBI. We're also collaborating with researchers at the University of Pennsylvania to compare mitochondrial function after head injury in different clinically relevant models.
The Daniel Weinberger Laboratory focuses on the neurobiological mechanisms of genetic risk for developmental brain disorders. We study the genetic regulation of the transcriptome in normal human brain across the human life span and in brains from patients with various psychiatric disorders. We also study the impact of genetic variation on aspects of human brain development and function linked with risk for schizophrenia and related psychiatric disorders. Our lab uses unique molecular and clinical datasets and biological materials from a large sample of families with affected and unaffected offspring and normal volunteers. These datasets include DNA, lymphoblast and fibroblast cell lines, and extensive quantitative phenotypes related to genetic risk for schizophrenia, including detailed cognitive assessments and various neuroimaging assays. In other research, we are working on a human brain transcriptome project that is RNA sequencing over 1,000 human brain samples in various regi...ons and based also on sorting of specific celliular phentypes. We are exploring the molecular processing of the gene and its implications for cognition and aspects of human temperament. view more
The David Linden Laboratory has used both electrode and optical recording in cerebellar slice and culture model systems to explore the molecular requirements for induction and expression of these phenomena. Along the way, we discovered a new form of plasticity. In addition, we have expanded our analysis to include use-dependent synaptic and non-synaptic plasticity in the cerebellar output structure, the deep nuclei.
Our investigations are central to understanding the cellular substrates of information storage in a brain area where the behavioral relevance of the inputs and outputs is unusually well defined. In addition, our investigations have potential clinical relevance for cerebellar motor disorders and for disorders of learning and memory generally.
Utilizing a combination of tissue-based, cell-based, and molecular approaches, our research goals focus on abnormal telomere biology as it relates to cancer initiation and tumor progression, with a particular interest in the Alternative Lengthening of Telomeres (ALT) phenotype. In addition, our laboratories focus on cancer biomarker discovery and validation with the ultimate aim to utilize these novel tissue-based biomarkers to improve individualized prevention, detection, and treatment strategies.
The Connor Laboratory focuses on understanding the neural algorithms that make object vision possible. The goal of our research is to explain the neural basis of visual experience and contribute to designs for more powerful machine vision systems and brain-machine interfaces.
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
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.
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.
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
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
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