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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.

    Research Areas: biomedicine, soft tissues, biomedical engineering, organs

    Principal Investigator

    Andrew Douglas, Ph.D.

    Department

    Biomedical Engineering

  • Andrew Laboratory: Center for Cell Dynamics

    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.

    Research Areas: immunology, cancer, epithelial tube, nervous system, molecular biology

    Lab Website

    Principal Investigator

    Deborah Andrew, M.S., Ph.D.

    Department

    Cell Biology

  • Cardiology Bioengineering Laboratory

    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.
    view more

    Research Areas: magnetic resonance imaging, CPR models, cardiac mechanics, MRI-guided therapy, ischemic tachycardia, arrhythmia, cardiology, sudden cardiac death, cardiopulmonary resuscitation, computational modeling

    Lab Website

    Principal Investigator

    Henry Halperin, M.D.

    Department

    Medicine

  • 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

    Research Areas: antiretroviral drugs, infectious disease, HIV protease inhibitors, HIV, drugs, accelerator mass spectrometry

    Principal Investigator

    Charles Flexner, M.D.

    Department

    Medicine

  • 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

    Research Areas: Head and neck squamous cell carcinoma, Human papillomavirus, Alternative splicing, epigenetics, Chromatin structure, Cancer genomics, head and neck cancer

  • Elisseeff Lab

    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

    Research Areas: stem cells, biomedical engineering, tissues

    Lab Website

    Principal Investigator

    Jennifer Elisseeff, Ph.D.

    Department

    Ophthalmology

  • 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.

    Research Areas: energy metabolism, insulin resistance, hormones, diabetes, metabolic homeostasis

    Principal Investigator

    Guang Wong, Ph.D.

    Department

    Physiology

  • In-vivo Cellular and Molecular Imaging Center

    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.

    Research Areas: optical imaging, molecular characterization of tumor tissue, bioinformatics, molecular oncology, biostatistics, probe development, molecular characterization of cells, cancer imaging

  • J. Marie Hardwick Laboratory

    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

    Research Areas: cell death

  • 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.

    Research Areas: cancer, molecular genetics, genomics, pathogenesis, liver diseases, hepatocellular carcinoma

    Principal Investigator

    James Hamilton, M.D.

    Department

    Medicine

  • Jeremy Nathans Laboratory

    The Jeremy Nathans Laboratory is focused on neural and vascular development, and the role of Frizzled 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.

    Research Areas: vascular development, biochemistry, cell biology, neurodevelopment, genomics, Frizzled receptors, neuroscience

  • Kenneth W. Kinzler Laboratory

    Dr. Kinzler’s laboratory has focused on the genetics of human cancer. They have identified a variety of genetic mutations that underlie cancer, including mutations of the APC pathway that appear to initiate the majority of colorectal cancers and IDH1/2 mutations that underlying many gliomas. In addition, they have developed a variety of powerful tools for analysis of expression and genetic alterations in cancer.
    Most recently, they have pioneered integrated whole genome analyses of human cancers through expression, copy number, and mutational analyses of all the coding genes in several human cancer types including colorectal, breast, pancreatic and brain. The identification of genetic differences between normal and tumor tissues provide new therapeutic targets, new opportunities for the early diagnosis of cancer, and important insights into the neoplastic process.

    Research Areas: cancer, molecular genetics

    Lab Website

    Principal Investigator

    Kenneth Kinzler, Ph.D.

    Department

    Oncology

  • Mass Spectrometry Core

    The Mass Spectrometry Core identifies and quantifies proteins that change expression in well-characterized protein fractions from cancerous cells or tissues. This includes identifying and quantifying changes in binding partners and post-translational modifications. Column chromatography and gel electrophoresis-based one and two-dimensional separations of protein complexes coupled to mass spectrometry are used. Techniques such as difference gel electrophoresis (DIGE), isobaric tag for relative and absolute quantitation (iTRAQ) and 18O-labeling as well as non-labeling methods (MudPit, multi-dimensional protein identification technology) are available for quantifying relative differences in protein expression and post-translational modifications. We developed methods to detect post-translational modifications such as LCMS methods to accurately determine the intact mass of proteins, selective fluorescent labeling of S-nitrosothiols (S-FLOS) to detect nitrosated cysteines in proteins, and i...on mapping methods to map post-translational modifications that produce a signature mass or mass difference when the modified peptide is fragmented. view more

    Research Areas: mass spectrometry, proteomics, cancer

  • Molecular Mechanisms of Cellular Mechanosensing (Robinson Lab)

    The Robinson Lab studies the way in which mechanical stress guide and direct the behavior of cells, including when they are part of tissues, organs and organ systems.

    Research Areas: cellular mechanosensing, tissues, organs, molecular biology

  • 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.

    Research Areas: imaging, protein trafficking, diarrhea, bioinformatics, molecular biology

    Principal Investigator

    Nicholas Zachos, Ph.D.

    Department

    Medicine

  • Ocular Vasculogenesis and Angiogenesis Lab (OVAL)

    The lab studies the development of blood vessels in the eye and how they change in diseases like retinopathy of prematurity, sickle cell and diabetic retinopathies, and age-related macular degeneration (AMD). The ultimate goal of the lab is to develop a new generation of therapies that, when delivered to the eye, allow the tissues of the eye to essentially treat themselves only when needed. The goal is to have the tissues generate their own therapeutics when needed, and stop production when the condition is resolved. These therapies will help reduce the need for repeated treatment and provide focused therapy, rather than treating the body with chemicals.

    Research Areas: vascular development, age-related mascular degeneration, sickle cell diseases, nanotechnology, retinopathy of prematurity, diabetic retinopathy

    Lab Website

    Principal Investigator

    Gerard Lutty, Ph.D.

    Department

    Ophthalmology

  • Robert Anders Lab

    Dr. Anders’ laboratory focuses on the basic processes that lead to cancer. His team approaches these questions through the use of both experimental models and examination of human tissues. His team is specifically interested in interrogating the immune microenvironment of cancer, detecting circulating cancer cells and preventing cancer metastasis.

    Research Areas: cancer, translational research, immunotherapy, liver cancer

    Lab Website

    Principal Investigator

    Robert Anders, M.D., Ph.D.

    Department

    Oncology
    Pathology

  • Seth Blackshaw Lab

    The Seth Blackshaw Lab uses functional genomics and proteomics to rapidly identify the molecular mechanisms that regulate cell specification and survival in both the retina and hypothalamus. We have profiled gene expression in both these tissues, from the start to the end of neurogenesis, characterizing the cellular expression patterns of more than 1,800 differentially expressed transcripts in both tissues. Working together with the lab of Heng Zhu in the Department of Pharmacology, we have also generated a protein microarray comprised of nearly 20,000 unique full-length human proteins, which we use to identify biochemical targets of developmentally important genes of interest.

    Research Areas: retina, central nervous system, biochemistry, hypothalamus, proteomics, genomics

    Lab Website

    Principal Investigator

    Seth Blackshaw, Ph.D.

    Department

    Neuroscience

  • Sheng Wu Laboratory

    The Sheng Wu Laboratory studies the insulin/androgen receptor (AR) actions on the developmental and regulation of the reproductive and metabolic functions. We use multiple animal models (obesity, androgen implantation, and conditional knockout) to investigate the pathophysiology of polycystic ovarian syndrome (PCOS) and the developmental factors and their target tissues that contribute to PCOS manifestation.

    Research Areas: reproduction, insulin, polycystic ovarian syndrome, endocrinology, androgen receptor

    Principal Investigator

    Sheng Wu, M.Sc., Ph.D.

    Department

    Pediatrics

  • The Arking Lab

    The Arking Lab studies the genomics of complex human disease, with the primary goal of identifying and characterizing genetics variants that modify risk for human disease. The group has pioneered the use of genome-wide association studies (GWAS), which allow for an unbiased screen of virtually all common genetic variants in the genome. The lab is currently developing improved GWAS methodology, as well as exploring the integration of additional genome level data (RNA expression, DNA methylation, protein expression) to improve the power to identify specific genetic influences of disease.

    The Arking Lab is actively involved in researching:
    • autism, a childhood neuropsychiatric disorder
    • cardiovascular genomics, with a focus on electrophysiology and sudden cardiac death (SCD)
    • electrophysiology is the study of the flow of ions in biological tissues

    Dan E. Arking, PhD, is an associate professor at the McKusick-Nathans Institute of Genetic Medicine and Department of Medicine, D...ivision of Cardiology, Johns Hopkins University. view more

    Research Areas: autism, genetics, aging, cardiovascular diseases, sudden cardiac death

    Principal Investigator

    Dan Arking, Ph.D.

    Department

    Medicine

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