Researchers in the Center for Cell Dynamics study spatially and temporally regulated molecular ...events in living cells, tissues and organisms. The team develops and applies innovative biosensors and imaging techniques to monitor dozens of critical signaling pathways in real time. The new tools help them investigate the fundamental cellular behaviors that underlie embryonic development, wound healing, cancer progression, and functions of the immune and nervous systems. view more

Our long-term goal is to investigate the mechanisms by which genetic factors such as PPARG and ...C/EBPs orchestrate formation of fat cells and adipose tissues as a whole. We use computer simulations and biological models in answering major questions in the field. Currently, we seek to determine genetic factors that independently regulate PPARG isoform 2 but not isoform 1 (and vice-versa). The overall aim is to develop a therapeutic strategy where the desirable effects of one isoform in tackling insulin resistance could be harvested in the absence of the other isoform. view more

The Cardiology Bioengineering Laboratory, located in the Johns Hopkins Hospital, focuses on the... applications of advanced imaging techniques for arrhythmia management. The primary limitation of current fluoroscopy-guided techniques for ablation of cardiac arrhythmia is the inability to visualize soft tissues and 3-dimensional anatomic relationships.

Implementation of alternative advanced modalities has the potential to improve complex ablation procedures by guiding catheter placement, visualizing abnormal scar tissue, reducing procedural time devoted to mapping, and eliminating patient and operator exposure to radiation.

Active projects include
• Physiological differences between isolated hearts in ventricular fibrillation and pulseless electrical activity
• Successful ablation sites in ischemic ventricular tachycardia in a porcine model and the correlation to magnetic resonance imaging (MRI)
• MRI-guided radiofrequency ablation of canine atrial fibrillation, and diagnosis and intervention for arrhythmias
• Physiological and metabolic effects of interruptions in chest compressions during cardiopulmonary resuscitation

Henry Halperin, MD, is co-director of the Johns Hopkins Imaging Institute of Excellence and a
professor of medicine, radiology and biomedical engineering. Menekhem M. Zviman, PhD is the laboratory manager.
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A. Laboratory activities include the use of accelerator mass spectrometry (AMS) techniques to m...easure intracellular drugs and drugs metabolites. AMS is a highly sensitive method for detecting tracer amounts of radio-labeled molecules in cells, tissues, and body fluids. We have been able to measure intracellular zidovudine triphosphate (the active anabolite of zidovudine) in peripheral blood mononuclear cells from healthy volunteers given small doses of 14C-zidovudine, and have directly compared the sensitivity of AMS to traditional LC/MS methods carried out in our laboratory.

B. Clinical research activities investigate the clinical pharmacology of new anti-HIV therapies and drug combinations. Specific drug classes studied include HIV reverse transcriptase inhibitors, protease inhibitors, entry inhibitors (selective CCR5 and CXCR4 antagonists), and integrase inhibitors. Scientific objectives of clinical studies include characterization of early drug activity, toxicity, and pharmacokinetics. Additional objectives are characterization of pathways of drug metabolism, and identification of clinically significant harmful and beneficial drug interactions mediated by hepatic and intestinal cytochrome P450 isoforms. view more

The mission of the Elisseeff Lab is to engineer technologies to repair lost tissues. We aim to ...bridge academic research and technology discovery to treat patients and address clinically relevant challenges related to tissue engineering. To accomplish this goal we are developing and enabling materials, studying biomaterial structure-function relationships and investigating mechanisms of tissue development to practically rebuild tissues. The general approach of tissue engineering is to place cells on a biomaterial scaffold that is designed to provide the appropriate signals to promote tissue development and ultimately restore normal tissue function in vivo. Understanding mechanisms of cellular interactions (both cell-cell and cell-material) and tissue development on scaffolds is critical to advancement of the field, particularly in applications employing stem cells. Translation of technologies to tissue-specific sites and diseased environments is key to better design, understanding, and ultimately efficacy of tissue repair strategies. We desire to translate clinically practical strategies, in the form of biomaterials/medical devices, to guide and enhance the body's natural capacity for repair. To accomplish the interdisciplinary challenge of regenerative medicine research, we maintain a synergistic balance of basic and applied/translational research. view more

The Wong Lab seeks to understand mechanisms employed by cells and tissues to maintain metabolic... homeostasis. We are currently addressing how adipose- and skeletal muscle-derived hormones (adipokines and myokines), discovered in our lab, regulate tissue crosstalk and signaling pathways to control energy metabolism. We use transgenic and knockout mouse models, as well as cell culture systems, to address the role of the CTRP family of hormones in physiological and disease states. We also aim to identify the receptors that mediate the biological functions of CTRPs. view more

The In-vivo Cellular and Molecular Imaging Center conducts multidisciplinary research on cellul...ar 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. view more

Our research is focused on understanding the basic mechanisms of programmed cell death in disea...se pathogenesis. Billions of cells die per day in the human body. Like cell division and differentiation, cell death is also critical for normal development and maintenance of healthy tissues. Apoptosis and other forms of cell death are required for trimming excess, expired and damaged cells. Therefore, many genetically programmed cell suicide pathways have evolved to promote long-term survival of species from yeast to humans. Defective cell death programs cause disease states. Insufficient cell death underlies human cancer and autoimmune disease, while excessive cell death underlies human neurological disorders and aging. Of particular interest to our group are the mechanisms by which Bcl-2 family proteins and other factors regulate programmed cell death, particularly in the nervous system, in cancer and in virus infections. Interestingly, cell death regulators also regulate many other cellular processes prior to a death stimulus, including neuronal activity, mitochondrial dynamics and energetics. We study these unknown mechanisms.

We have reported that many insults can trigger cells to activate a cellular death pathway (Nature, 361:739-742, 1993), that several viruses encode proteins to block attempted cell suicide (Proc. Natl. Acad. Sci. 94: 690-694, 1997), that cellular anti-death genes can alter the pathogenesis of virus infections (Nature Med. 5:832-835, 1999) and of genetic diseases (PNAS. 97:13312-7, 2000) reflective of many human disorders. We have shown that anti-apoptotic Bcl-2 family proteins can be converted into killer molecules (Science 278:1966-8, 1997), that Bcl-2 family proteins interact with regulators of caspases and regulators of cell cycle check point activation (Molecular Cell 6:31-40, 2000). In addition, Bcl-2 family proteins have normal physiological roles in regulating mitochondrial fission/fusion and mitochondrial energetics to facilitate neuronal activity in healthy brains. view more

The main research interests of the James Hamilton Lab are the molecular pathogenesis of hepatoc...ellular carcinoma and the development of molecular markers to help diagnose and manage cancer of the liver. In addition, we are investigating biomarkers for early diagnosis, prognosis and response to various treatment modalities. Results of this study will provide a molecular classification of HCC and allow us to identify targets for chemoprevention and treatment. Specifically, we extract genomic DNA and total RNA from liver tissues and use this genetic material for methylation-specific PCR (MSP), cDNA microarray, microRNA microarray and genomic DNA methylation array experiments. view more

The Jeremy Nathans Laboratory is focused on neural and vascular development, and the role of Fr...izzled receptors in mammalian development. We use gene manipulation in the mouse, cell culture models, and biochemical reconstitution to investigate the relevant molecular events underlying these processes, and to genetically mark and manipulate cells and tissues. Current experiments are aimed at defining additional Frizzled-regulated processes and elucidating the molecular mechanisms and cell biologic results of Frizzled signaling within these various contexts. Complementing these areas of biologic interest, we have ongoing technology development projects related to genetically manipulating and visualizing defined cell populations in the mouse, and quantitative analysis of mouse visual system function. view more