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Nicholas Zachos Lab
Researchers in the Nicholas Zachos Lab work to understand variations in protein trafficking that occur during pathophysiological conditions that cause ion and water transport that result in diarrhea. We recently identified a clathrin-independent endocytic pathway responsible for elevated intracellular calcium-mediated inhibition of NHE3 activity in intestinal epithelial cells. We use advanced imaging techniques, including confocal and multi-photon microscopy, to characterize protein trafficking of intestinal transporters. We also perform functional assays using fluorescent probes (ratiometric and non-ratiometric) to measure ion transport in cell culture models, intact intestinal tissues and human small intestinal enteroids.
How do brain dynamics give rise to our sensory experience of the world? The O'Connor lab works to answer this question by taking advantage of the fact that key architectural features of the mammalian brain are similar across species. This allows us to leverage the power of mouse genetics to monitor and manipulate genetically and functionally defined brain circuits during perception. We train mice to perform simple perceptual tasks. By using quantitative behavior, optogenetic and chemical-genetic gain- and loss-of-function perturbations, in vivo two-photon imaging, and electrophysiology, we assemble a description of the relationship between neural circuit function and perception. We work in the mouse tactile system to capitalize on an accessible mammalian circuit with a precise mapping between the sensory periphery and multiple brain areas. Our mission is to reveal the neural circuit foundations of sensory perception; to provide a framework to understand how circuit dysfunction causes ...mental and behavioral aspects of neuropsychiatric illness; and to help others fulfill creative potential and contribute to human knowledge. view more
The O’Rourke Lab uses an integrated approach to study the biophysics and physiology of cardiac cells in normal and diseased states.
Research in our lab has incorporated mitochondrial energetics, Ca2+ dynamics, and electrophysiology to provide tools for studying how defective function of one component of the cell can lead to catastrophic effects on whole cell and whole organ function. By understanding the links between Ca2+, electrical excitability and energy production, we hope to understand the cellular basis of cardiac arrhythmias, ischemia-reperfusion injury, and sudden death.
We use state-of-the-art techniques, including single-channel and whole-cell patch clamp, microfluorimetry, conventional and two-photon fluorescence imaging, and molecular biology to study the structure and function of single proteins to the intact muscle. Experimental results are compared with simulations of computational models in order to understand the findings in the context of the system as a whole....
Ongoing studies in our lab are focused on identifying the specific molecular targets modified by oxidative or ischemic stress and how they affect mitochondrial and whole heart function.
The motivation for all of the work is to understand
• how the molecular details of the heart cell work together to maintain function and
• how the synchronization of the parts can go wrong
Rational strategies can then be devised to correct dysfunction during the progression of disease through a comprehensive understanding of basic mechanisms.
Brian O’Rourke, PhD, is a professor in the Division of Cardiology and Vice Chair of Basic and Translational Research, Department of Medicine, at the Johns Hopkins University. view more
Pediatric Cardiology Core Imaging Laboratory
The lab’s assets include three MRI systems available for pediatric studies, cardiac imaging processing, cardiovascular imaging and therapeutic ultrasound. A robust echocardiogram program conducts 10,000 transthoracic echocardiograms and 1,300 fetal echocardiograms per year, and maintains a database with 10 years of data.
Psychiatric Neuroimaging (PNI) is active in neuropsychiatric research using imaging methods such as MRI, fMRI, PET and DTI to understand the mechanisms and brain networks underlying human cognition. PNI faculty have published hundreds of papers on a variety of brain disorders which include but are not limited to Alzheimer's disease, Parkinson's disease, bipolar disorder, and eating disorders. Faculty in the division have been awarded numerous peer-reviewed grants by the National Institutes of Health, foundations and other funding organizations.
Quantitative Imaging Technologies
Research in the Quantitative Imaging Technologies lab — a component of the Imaging for Surgery, Therapy and Radiology (I-STAR) Lab — focuses on novel technologies to derive accurate structural and physiological measurements from medical images. Our team works on optimization of imaging systems and algorithms to support a variety of quantitative applications, with recent focus on orthopedics and bone health. For example, we have developed an ultra-high resolution imaging chain for an orthopedic CT system to enable in-vivo measurements of bone microstructure. Our interests also include automated methods to extract quantitative information from images, including anatomical and micro-structural measurements, and shape analysis.
The main research goals of my laboratory are: (1) to identify and study the biology of novel cancer selective targets whose enzymatic function can be exploited for therapeutic and diagnostic purposes; (2) to develop methods to target novel agents for activiation by these cancer selective targets while avoiding or minimizing systemic toxicity; (3) to develop novel agents for imaging cancer sites at earliest stages. To accomplish these objectives the lab has originally focused on the development of prodrugs or protoxins that are inactive when given systemically via the blood and only become activated by tumor or tissue specific proteases present within sites of tumor. Using this approach, we are developing therapies targeted for activation by the serine proteases prostate-specific antigen (PSA), human glandular kallikrein 2 (hK2) and fibroblast activation protein (FAP) as well as the membrane carboxypeptidase prostate-specific membrane antigen (PSMA). One such approach developed in the l...ab consists of a potent bacterial protoxin that we have reengineered to be selectively activated by PSA within the Prostate. This PSA-activated toxin is currently being tested clinically as treatment for men with recurrent prostate cancer following radiation therapy. In a related approach, a novel peptide-cytotoxin prodrug candidate that is activated by PSMA has been identified and is this prodrug candidate is now entering early phase clinical development. In addition, we have also identified a series of potent inhibitors of PSA that are now under study as drug targeting and imaging agents to be used in the treatment and detection of prostate cancer.
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 the...se questions, we use an integrated approach that includes in vivo models, imaging, molecular biology, biochemistry, developmental biology, genetics and behavior. view less
Shelby Kutty Laboratory
Shelby Kutty, M.D., Ph.D., is an authority on cardiovascular imaging, including echocardiography, magnetic resonance imaging and computed tomography of congenital heart disease. His areas of academic interest have focused on myocardial function assessment, therapeutic ultrasound and cardiovascular outcomes. Kutty’s research includes developing new imaging technology applications such as a smartphone application that uses patients’ echocardiographic images to track their progress. His work gives pediatric cardiologists better ways to predict outcomes in their patients and provide the most effective and appropriate treatments.
The Sujatha Kannan Lab works to develop therapeutic strategies for preventing perinatal brain injuries from occurring during development. We use a unique combination of nanotechnology, animal model development and in vivo imaging to better understand the mechanism and progression of cellular and metabolic conditions that lead to perinatal brain injury, with a focus on autism and cerebral palsy.
The Pathak lab is within the Division of Cancer Imaging Research in the Department of Radiology and Radiological Science. We develop novel imaging methods, computational models and visualization tools to ‘make visible’ critical aspects of cancer, stroke and neurobiology. Our research broadly encompasses the following areas: Functional and Molecular Imaging; Clinical Biomarker Development; Image-based Systems Biology and Visualization and Computational Tools. We are dedicated to mentoring the next generation of imagers, biomedical engineers and visualizers. Additional information can be found at www.pathaklab.org or by emailing Dr. Pathak.
Venu Raman Research Lab
The Raman laboratory is within the Division of Cancer Imaging Research in the Department of Radiology and Radiological Science. The focus of the laboratory is bench-to-bed side cancer research. We integrate molecular and cellular biology, developmental biology, cancer biology, molecular imaging techniques to study cancer formation and progression. Many of the projects in the lab investigate dysregulated genes in cancer and the translatability of this information to a clinical setting. One such project is to functionally decipher the role of a RNA helicase gene, DDX3, in the biogenesis of multiple cancer types such as breast, lung, brain, sarcoma, colorectal and prostate. Additionally, using a rational drug design approach, a small molecule inhibitor of DDX3 (RK-33) was synthesized and its potential for clinical translation is being investigated.
The Weiss Lab, which features a multi-disciplinary team at Johns Hopkins as well as at Cedars Sinai Medical Center in Los Angeles, is dedicated to identifying the most important clinical, genetic, structural, contractile and metabolic causes of sudden cardiac death as well as the means to reverse the underlying pathology and lower risk.
Current projects include research into energy metabolism in human heart failure and creatine kinase metabolism in animal models of heart failure.
Robert G. Weiss, MD, is professor of medicine, Radiology and Radiological Science, at the Johns Hopkins University.
Wojciech Zbijewski Lab
Research in the Wojciech Zbijewski Lab — a component of the Imaging for Surgery, Therapy and Radiology (I-STAR) Lab — focuses on system modeling techniques to optimize the x-ray CT imaging chain. We’re specifically interested in: 1) using numerical models to improve the task-based optimization of image quality; 2) exploring advanced modeling of physics in statistical reconstruction; 3) using accelerated Monte Carlo methods in CT imaging; and 4) conducting experimental validation of such approaches and applying them to the development of new imaging methods.
Dr. Wu leads a multi-disciplinary team with collaborators from the Bloomberg School of Public Health, JHU Whiting School of Engineering, and JHU Krieger School of Arts and Sciences. She conducts ongoing investigations with the Multicenter AIDS Cohort Study and Women’s Inter-agency Health Study. Her lab’s goals are to develop, implement, and validate novel imaging-based metrics of cardiac structure and function to improve risk prediction and stratification at the individual patient-level.
Predictors of Sudden Cardiac Death by Magnetic Resonance Imaging
Subclinical myocardial disease in people living with HIV
Individualized risk prediction
Cardiac structural and mechanical modeling
The Zanvyl Krieger Mind/Brain Institute is dedicated to the study of the neural mechanisms of higher brain functions using modern neurophysiological, anatomical and computational techniques. Our researchers use various approaches to understand information processing and its influence on perception, memory, abstract thought, complex behavior and consciousness. Systems and cognitive laboratories use neurophysiology, brain imaging and psychophysics to develop a quantitative, network-level understanding of cognitive information processing. Other researchers use analytical approaches such as system identification, dimensionality reduction, information theory and network modeling to understand information processing. Other areas of research in the Institute include the study of how visual and tactile information processing leads to perception and understanding of two- and three-dimensional objects. Another focus is on neural processing and recognition of speech and other complex sounds. St...ill other laboratories study neural mechanisms of attention, memory formation, motor learning, decision-making and executive control of behavior. view more
Dr. Bhujwalla’s lab promotes preclinical and clinical multimodal imaging applications to understand and effectively treat cancer. The lab’s work is dedicated to the applications of molecular imaging to understand cancer and the tumor environment. Significant research contributions include 1) developing ‘theranostic agents’ for image-guided targeting of cancer, including effective delivery of siRNA in combination with a prodrug enzyme 2) understanding the role of inflammation and cyclooxygenase-2 (COX-2) in cancer using molecular and functional imaging 3) developing noninvasive imaging techniques to detect COX-2 expressing in tumors 4) understanding the role of hypoxia and choline pathways to reduce the stem-like breast cancer cell burden in tumors 5) using molecular and functional imaging to understand the role of the tumor microenvironment including the extracellular matrix, hypoxia, vascularization, and choline phospholipid metabolism in prostate and breast cancer invasion and metast...asis, with the ultimate goal of preventing cancer metastasis and 6) molecular and functional imaging characterization of cancer-induced cachexia to understand the cachexia-cascade and identify novel targets in the treatment of this condition. view less