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Displaying 1 to 16 of 16 results for enzymes

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  • Bioenergetics Core

    Mitochondrial dysfunction has long been a consistent observation in Parkinson's disease. To understand the consequences of Parkinson's disease causing genetic mutations on the function of mitochondria, the Bioenergetics Core B will provide the following analyses to the projects in the Udall Center at Johns Hopkins: (1) Measuring rates of respiration, oxygen consumption and ATP generation, (2) Measuring calcium dynamics, (3) Measuring reactive oxygen and reactive nitrogen species, (4) Measuring the activity of the electron transport chain enzymes and metabolic enzymes, and (5) Measuring plasma versus mitochondrial membrane potential and mitochondrial membrane permeability

    Research Areas: enzymes, cell biology, bioenergetics, respiration, Parkinson's disease, mitochondria, neurology

    Lab Website

    Principal Investigator

    Valina Dawson, Ph.D.

    Department

    Neurology

  • Caren L. Freel Meyers Laboratory

    The long-term goal of the Caren L. Freel Meyers Laboratory is to develop novel approaches to kill human pathogens, including bacterial pathogens and malaria parasites, with the ultimate objective of developing potential therapeutic agents.

    Toward this goal, we are pursuing studies of bacterial isoprenoid biosynthetic enzymes comprising the methylerythritol phosphate (MEP) pathway essential in many human pathogens. Studies focus on understanding mechanism and regulation in the pathway toward the development of selective inhibitors of isoprenoid biosynthesis. Our strategies for creating new anti-infective agents involve interdisciplinary research in the continuum of organic, biological and medicinal chemistry. Molecular biology, protein expression and biochemistry, and synthetic chemistry are key tools for our research.

    Research Areas: bacterial pathogens, biochemistry, enzymes, infectious disease, protein expression, synthetic chemistry, isoprenoid biosynthesis, malaria, pharmacology, chemistry, molecular biology

  • Christopher A. Ross Lab

    Dr. Ross and his research team have focused on Huntington's disease and Parkinson's disease, and now are using insights from these disorders to approach more complex diseases such as schizophrenia and bipolar disorder. They use biophysical and biochemical techniques, cell models, and transgenic mouse models to understand disease processes, and to provide targets for development of rational therapeutics. These then can provide a basis for developing small molecule interventions, which can be used both as probes to study biology, and if they have favorable drug-like properties, for potential therapeutic development. We have used two strategies for identifying lead compounds. The first is the traditional path of identification of specific molecular targets, such as enzymes like the LRRK2 kinase of Parkinson’s disease. Once structure is known, computational approaches or fragment based lead discovery, in collaboration, can be used. The second is to conduct phenotypic screens using ce...ll models, or in a collaboration, natural products in a yeast model. Once a lead compound is identified, we use cell models for initial tests of compounds, then generate analogs, and take compounds that look promising to preclinical therapeutic studies in animal models. The ultimate goal is to develop therapeutic strategies that can be brought to human clinical trials, and we have pioneered in developing biomarkers and genetic testing for developing strategies. view more

    Research Areas: psychiatric disorders

  • Daniel Raben Laboratory

    The Raben Laboratory is focused on understanding the biochemistry and chemistry underlying the molecular aspects involved in regulating lipid metabolizing signaling enzymes and the physiological roles of this regulation. Controlling lipid-metabolizing enzymes involves modulating their sub-cellular distribution and their intrinsic enzymatic activity. Researchers in the Raben laboratory examine three families of lipid-metabolizing signaling enzymes: diacylglycerol kinases, phospholipases D, and phospholipases C.

    Research Areas: biochemistry, lipid-metabolizing enzymes, cellular signaling, chemistry

    Principal Investigator

    Daniel Raben, Ph.D.

    Department

    Biological Chemistry

  • Erika Darrah Lab

    The Erika Darrah Lab is primarily interested in the mechanisms underlying the development and progression of autoimmunity in rheumatoid arthritis (RA), with a particular focus on the peptidyl arginine deiminase (PAD) enzymes. We’re focused on understanding the development of PAD4-activating autoantibodies over time and how they contribute to the development of erosive disease. Studies are underway to determine if the newly discovered antibody is mimicking a naturally occurring PAD4 binding partner and to identify potentially pro-inflammatory effects of citrullinated proteins on effector cells of the immune system.

    Research Areas: antibodies, autoimmune diseases, peptidylarginine deiminase enzymes, rheumatoid arthritis

    Lab Website

    Principal Investigator

    Erika Darrah, Ph.D.

    Department

    Medicine

  • Felipe Andrade Laboratory

    Research in the laboratory of Felipe Andrade, M.D., Ph.D., focuses on the mechanisms of systemic autoimmune diseases, particularly as they relate to the role of cytotoxic granule proteases in autoimmunity and viral clearance, mechanisms of autoantigen citrullination and pathways that control immune effector functions in autoimmune diseases. We currently focus on two principal areas: (1) defining the mechanisms that generate citrullinated autoantigens in vivo in rheumatoid arthritis and (2) understanding the pathways that control the activity of the peptidylarginine deiminase (PAD) enzymes in human neutrophils.

    Research Areas: autoantigens, autoimmune diseases, cytotoxic granule proteases, peptidylarginine deiminase enzymes, rheumatoid arthritis

    Principal Investigator

    Felipe Andrade, M.D., Ph.D.

    Department

    Medicine

  • Frueh Laboratory

    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.

    Research Areas: enzymes, proteomics, imaging, drugs, antibiotics, nuclear magnetic resonance, molecular biology

  • Richard F. Ambinder Lab

    Epstein-Barr virus and Kaposi's sarcoma herpesvirus are found in association with a variety of cancers. Our laboratory studies are aimed at better defining the role(s) of the virus in the pathogenesis of these diseases and the development of strategies to prevent, diagnose or treat them. We have become particularly interested in the unfolded protein response in activation of latent viral infection. Among the notions that we are exploring is the possibility that activation of virus-encoded enzymes will allow the targeted delivery of radation. In addition, we are investigating a variety of virus-related biomarkers including viral DNA, antibody responses, and cytokine measurements that may be clinically relevant.

    Research Areas: virology, antiviral therapy

  • Richard John Jones Lab

    The Richard J. Jones Lab studies normal and cancerous stem cells in order to make clinical improvements in areas such as blood and marrow transplantation (BMT). We discovered one of the most common stem-cell markers, Aldefluor, which identifies cells based on their expression of aldehyde dehydrogenase 1 (ALDH1), and have used this marker to detect and characterize normal stem cells and cancer stem cells from many hematologic malignancies. We also developed post-transplant cyclophosphamide and effective related haploidentical BMT.

    Research Areas: enzymes, stem cells, blood and marrow transplantation, leukemia, cancer

    Principal Investigator

    Richard Jones, M.D.

    Department

    Medicine

  • Saraswati Sukumar Lab

    Our lab is focused on using comprehensive gene expression, methylation and sequencing and metabolomics analysis to identify alterations in breast cancer, and exploiting these for early detection and therapy. Among deferentially expressed genes, our lab has focused on the HOX genes. HOX genes are intimately involved in the development of resistance to both chemotherapy and to agents targeting the estrogen receptor. Our work explores the alternate pathways that are activated by HOX proteins leading to this resistance and novel treatments to overcome resistance in both tissue culture and xenograft models. In addition, epigenetically silenced genes and a metabolic reprogramming in tumors also trigger novel early detection and therapeutic strategies. We are testing the utility of differentiation therapy through reactivating RAR-beta in breast cancer using histone deacetylase inhibitors with great success. Also, we are targeting enzymes involved in gluconeogenesis and glycolysis with small ...molecule FDA-approved antimetabolites to achieve antitumor effects. view more

    Research Areas: breast cancer, genetics

    Lab Website

    Principal Investigator

    Saraswati Sukumar, Ph.D.

    Department

    Oncology

  • Sean T. Prigge Lab

    Current research in the Sean T. Prigge Lab explores the biochemical pathways found in the apicoplast, an essential organelle found in malaria parasites, using a combination of cell biology and genetic, biophysical and biochemical techniques. We are particularly focused on the pathways used for the biosynthesis and modification of fatty acids and associated enzyme cofactors, including pantothenate, lipoic acid, biotin and iron-sulfur clusters. We want to better understand how the cofactors are acquired and used, and whether they are essential for the growth of blood-stage malaria parasites.

    Research Areas: biochemistry, enzymes, immunology, apicoplasts, malaria, molecular microbiology

  • Shanthini Sockanathan Laboratory

    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 more

    Research Areas: glia, biochemistry, neurons, imaging, developmental biology, genomics, spinal cord, behavior, molecular biology

    Lab Website

    Principal Investigator

    Shanthini Sockanathan, D.Phil.

    Department

    Neuroscience

  • Stivers Lab

    The Stivers Lab is broadly interested in the biology of the RNA base uracil when it is present in DNA. Our work involves structural and biophysical studies of uracil recognition by DNA repair enzymes, the central role of uracil in adapative and innate immunity, and the function of uracil in antifolate and fluoropyrimidine chemotherapy. We use a wide breadth of structural, chemical, genetic and biophysical approaches that provide a fundamental understanding of molecular function. Our long-range goal is to use this understanding to design novel small molecules that alter biological pathways within a cellular environment. One approach we are developing is the high-throughput synthesis and screening of small molecule libraries directed at important targets in cancer and HIV-1 pathogenesis.

    Research Areas: biophysics, enzymes, cell biology, uracil, cancer, HIV, DNA, RNA

  • Structural Enzymology and Thermodynamics Group

    The Structural Enzymology and Thermodynamics Group uses a combination of molecular biology, biochemistry and structural biology to understand the catalytic mechanisms of several enzyme families. Additionally, researchers in the group are studying protein-ligand interactions using structural dynamics. They are able to apply their knowledge of the mechanisms of these enzymes and of binding energetics to develop targets for drug design.

    Research Areas: biochemistry, enzymes, structural biology, molecular biology

  • Urban Lab

    The Urban Lab studies rhomboid proteases--a class of enzymes that cut proteins to initiate signaling between cells as a form of communication that organizes embryo development. Current studies in the lab focus on the biophysics of how these enzymes function inside the cell membrane, where it's hard for catalysis to take place. Because rhomboid intramembrane proteolysis plays a central role in malaria infection and Parkinson's disease pathogenesis, these studies may have therapeutic implications.

    Research Areas: enzymes, cell biology, membrane biophysics, structural biology, synthetic chemistry, malaria, Parkinson's disease, rhomboid proteases

  • William G. Nelson Laboratory

    Normal and neoplastic cells respond to genome integrity threats in a variety of different ways. Furthermore, the nature of these responses are critical both for cancer pathogenesis and for cancer treatment. DNA damaging agents activate several signal transduction pathways in damaged cells which trigger cell fate decisions such as proliferation, genomic repair, differentiation, and cell death. For normal cells, failure of a DNA damaging agent (i.e., a carcinogen) to activate processes culminating in DNA repair or in cell death might promote neoplastic transformation. For cancer cells, failure of a DNA damaging agent (i.e., an antineoplastic drug) to promote differentiation or cell death might undermine cancer treatment.

    Our laboratory has discovered the most common known somatic genome alteration in human prostatic carcinoma cells. The DNA lesion, hypermethylation of deoxycytidine nucleotides in the promoter of a carcinogen-defense enzyme gene, appears to result in inactivation of th...e gene and a resultant increased vulnerability of prostatic cells to carcinogens.
    Studies underway in the laboratory have been directed at characterizing the genomic abnormality further, and at developing methods to restore expression of epigenetically silenced genes and/or to augment expression of other carcinogen-defense enzymes in prostate cells as prostate cancer prevention strategies.

    Another major interest pursued in the laboratory is the role of chronic or recurrent inflammation as a cause of prostate cancer. Genetic studies of familial prostate cancer have identified defects in genes regulating host inflammatory responses to infections.
    A newly described prostate lesion, proliferative inflammatory atrophy (PIA), appears to be an early prostate cancer precursor. Current experimental approaches feature induction of chronic prostate inflammation in laboratory mice and rats, and monitoring the consequences on the development of PIA and prostate cancer.
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    Research Areas: cellular biology, cancer, epigenetics, DNA

    Lab Website

    Principal Investigator

    William Nelson, M.D., Ph.D.

    Department

    Oncology

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