The In-vivo Cellular and Molecular Imaging Center conducts multidisciplinary research on cellular and molecular imaging related to cancer. We provide resources, such as consultation on biostatistics and bioinformatics and optical imaging and probe development, to understand and effectively treat cancer. Our molecular oncology experts consult on preclinical studies, use of human tissues, interpretation of data and molecular characterization of cells and tumor tissue.

Established in 2004, the MRB Molecular Imaging Service Center and Cancer Functional Imaging Core provides comprehensive molecular and functional imaging infrastructure to support the imaging research needs of the Johns Hopkins University faculty. Approximately 55-65 different Principal Investigators use the center annually. The MRB Molecular Imaging Service Center is located behind the barrier within the transgenic animal facility in the basement of MRB. The MRB location houses a 9.4T MRI/S scanner for magnetic resonance imaging and spectroscopy, an Olympus multiphoton microscope with in vivo imaging capability, a PET-CT scanner, a PET-SPECT scanner, and a SPECT-CT scanner for nuclear imaging, multiple optical imaging scanners including an IVIS Spectrum, and a LI COR near infrared scanner, and an ultrasound scanner. A brand new satellite facility in CRB2-LB03 opens in 2019 to house a simultaneous 7T PET-MR scanner, as well as additional imaging equipment, to meet the growing molecular and functional imaging research needs of investigators. To image with us, MRB Animal Facility training and Imaging Center Orientation are required to obtain access to the MRB Animal Facility and to the MRB Molecular Imaging Center (Suite B14). The MRB Animal Facility training group meets at 9:30 am on Thursdays at the Turner fountain/MRB elevator lobby. The Imaging Center orientation group meets at 1 pm on Thursdays at the Turner fountain, and orientation takes approximately 30 min. Please keep in mind that obtaining access to both facilities requires time, so please plan in advance.

Our research explores and integrates cutting-edge techniques in body composition analysis, nuclear endocrinology, metabolic and molecular imaging, and innovative machine learning methods.

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 metastasis, 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.

We investigate the brain networks and neurotransmitters involved in symptoms of movement disorders, such as Parkinson's disease, and the mechanisms by which modulating these networks through electrical stimulation affects these symptoms. We are particularly interested in the mechanisms through which neuromodulation therapies like deep brain stimulation affect non-motor brain functions, such as cognitive function and mood. We use imaging of specific neurotransmitters, such as acetylcholine and dopamine, to understand the changes in brain chemistry associated with the clinical effects of deep brain stimulation and to predict which patients are likely to have changes in non-motor symptoms following DBS. Through collaborations with our neurosurgery colleagues, we explore brain function by making recordings during DBS surgery during motor and non-motor tasks. Dr. Mills collaborates with researchers in the Department of Neurosurgery, the Division of Geriatric and Neuropsychiatry in the Department of Psychiatry and Behavioral Sciences and in the Division of Nuclear Medicine within the Department of Radiology to translate neuroimaging and neurophysiology findings into clinical applications.

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.

The Frueh Laboratory uses nuclear magnetic resonance (NMR) to study how protein dynamics can be modulated and how active enzymatic systems can be conformed. Non-ribosomal peptide synthetases (NRPS) are large enzymatic systems that biosynthesize secondary metabolites, many of which are used by pharmaceutical scientists to produce drugs such as antibiotics or anticancer agents. Dr. Frueh's laboratory uses NMR to study inter- and intra-domain modifications that occur during the catalytic steps of NRPS. Dr. Frueh and his team are constantly developing new NMR techniques to study these complicated enzymatic systems.

The Hey-Kyoung Lee Lab is interested in exploring the cellular and molecular changes that happen at synapses to allow memory storage. We use various techniques, including electrophysiological recording, biochemical and molecular analysis, and imaging, to understand the cellular and molecular changes that happen during synaptic plasticity. Currently, we are examining the molecular and cellular mechanisms of global homeostatic synaptic plasticity using sensory cortices as model systems. In particular, we found that loss of vision elicits global changes in excitatory synaptic transmission in the primary visual cortex. Vision loss also triggers specific synaptic changes in other primary sensory cortices, which we postulate underlies sensory compensation in the blind. One of our main research goals is to understand the mechanisms underlying such cross-modal synaptic plasticity. We are also interested in elucidating the events that occur in diseased brains. In collaboration with other researchers, we are analyzing various mouse models of Alzheimer's disease, especially focusing on the possible alterations in synaptic plasticity mechanisms.

The Penet lab is within the Division of Cancer Imaging Research in the Department of Radiology and Radiological Science. The lab research focuses on using multimodal imaging techniques to better understand the microenvironment and improve cancer early detection, especially in ovarian cancer. By combining MRI, MRS and optical imaging, we are studying the tumor microenvironment to understand the role of hypoxia, tumor vascularization, macromolecular transport and tumor metabolism in tumor progression, metastasis and ascites formation in orthotopic models of cancer. We also are studying the role of tumor-associated macrophages in tumor progression.

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.