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Andrew Douglas Lab
Research in the Andrew Douglas Lab investigates topics within the field of biomedical engineering. Our studies primarily focus on soft biological tissues and organs, such as the heart and tongue. Our current research areas include the nonlinear mechanics of solids, the mechanical response of compliant biological tissues, finite deformation elasticity, and the static and dynamic fracture of ductile materials.
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.
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.
Charles W. Flexner Laboratory
A. Laboratory activities include the use of accelerator mass spectrometry (AMS) techniques to measure 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 pharmacok...inetics. 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
Daria Gaykalova Lab
The Daria Gakalova Lab defines the functional role of epigenetics in transcriptional regulation of head and neck squamous cell carcinoma (HNSCC) progression. To evaluate the whole-genome distribution of various histone marks, her team is using chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-Seq) for primary tissues, a method recently developed by her lab. The research group of Daria Gaykalova was the first to demonstrate the cancer-specific distribution of H3K4me3 and H3K27ac marks and their role in cancer-related gene expression in HNSCC. The research showed that an aberrant chromatin alteration is a central event in carcinogenesis and that the therapeutic control of chromatin structure can prevent the primary of secondary cancerization. Further preliminary data suggest that the differential enrichment of these disease-specific histone marks and DNA methylation correlate with alternative splicing events (ASE) formation. For this project, Dr. Gaykalova... and her team employed a novel bioinformatical tool for the detection of cancer-specific ASEs. Through thorough functional validation of the individual ASEs, the lab demonstrated that each of them has a unique mechanism of malignant transformation of the cells. Due to high disease specificity, ASEs represent the perfect biomarkers of the neoantigens and have direct application to clinical practice. 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
Guang William Wong Lab
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.
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.
Our research is focused on understanding the basic mechanisms of programmed cell death in disease 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 cel...lular 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
James Hamilton Lab
The main research interests of the James Hamilton Lab are the molecular pathogenesis of hepatocellular 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.