Edward A. Doisy Department of Biochemistry

Primary Faculty

Education
Ph.D., 2002, University of Barcelona
Research Interests
Our laboratory is interested in sterol homeostasis and in the molecular mechanisms involved in the conversion of macrophages into foam cells. This latter process is particularly relevant in several human pathologies, including atherosclerosis and different pulmonary lipidosis syndromes.
Recent Publications
  • Impaired cholesterol efflux in senescent macrophages promotes age-related macular degeneration.
    Sene A, Khan AA, et al. Cell Metab. (2013) 17(4):549-61.
  • MicroRNA-144 regulates hepatic ABCA1 and plasma HDL following activation of the nuclear receptor FXR.
    de Aguiar Vallim T, Tarling E, et al. Circ Res. (2013) Mar 21 [Epub ahead of print].
  • Anti-miR-22 therapy does not alter the progression of atherosclerosis in low-density lipoprotein receptor-deficient mice.
    Marquart TJ, Wu J, et al. Arterioscler Thromb Vasc Biol. (2013) 33(3):455-8.
  • Cholesterol efflux analyses using stable isotopes and mass spectrometry.
    Brown RJ, Shao F, et al. Anal Biochem. (2012) 433(1):56-64.
  • miR-33 controls the expression of biliary transporters, and mediates statin-and diet-induced hepatotoxicity.
    Allen RM, Marquart TJ, et al. EMBO Mol Med. (2012) 4(9):882-95.
  • Mir-33 regulates cell proliferation and cell cycle progression.
    Cirera-Salinas D, Pauta M, et al. Cell Cycle. (2012) 11(5):922-33.
Education
Ph.D., 1987, California Institute of Technology
Research Interests
Our lab is interested in understanding how two distinct eukaryotic methionine aminopeptidases (MetAPs) function in the amino-terminal processing of eukaryotic proteins and its role in angiogenesis. Recently, the type-2 MetAP was found to be the molecular target for angiogenesis inhibitors, TNP-470 and ovalicin. Angiogenesis is the process of new blood vessel formation. It plays very important roles in both physiological states and a variety of pathological states.
Recent Publications
  • Molecular PINCERs® for biomarker analysis and their potential application in hepatitis C diagnosis.
    Tian L, Wang RE, Chang YH. Antivir Ther. (2012) 17:1437-42.
  • A homogeneous fluorescent sensor for human serum albumin.
    Wang RE, Tian L, Chang YH. J Pharm Biomed Anal. (2012) 63:165-9.
  • A homogeneous fluorescent assay for cAMP-phosphodiesterase enzyme activity.
    Tian L, Wang RE, Fei Y, Chang YH. J Biomol Screen. (2012) 17(3):409-14.
Education
Ph.D., 2005, Texas A&M University
Research Interests
Immune cells have direct and indirect interaction with other cells. The indirect interactions include the secretion of small protein ligands such as cytokines, chemokines, and growth factors for binding and activating receptors. Molecular details, however, of the binding mechanisms are still largely unknown. We are interested in understanding how these protein ligands interact with different receptors. We subsequently want to translate this information to develop small molecules modulating the protein ligands in a receptor-specific manner with therapeutic effects against inflammatory diseases and cancer. We use a variety of techniques, including biochemical and biophysical methods such as X-ray crystallography and NMR, high-throughput screening, virtual docking, biosensor-based label-free cellular assay system, as well as animal models of human diseases.
Recent Publications
  • Structural studies of small molecule inhibitors of MIF.
    Cho Y and Lolis E. The MIF handbook. (2012) World Scientific Publishing Co.
  • Drug repositioning and pharmacophore identification in the discovery of hookworm MIF inhibitors.
    Cho Y, Vermeire JJ, et al. Chem Biol. (2011) 18(9):1089-101.
  • Somatic and inherited mutations in K+ channel KCNJ5 cause aldosterone-producing adenomas and primary aldosteronism.
    Choi M, Scholl UI, et al. Science. (2011) 331(6018):768-72.
  • When anti-CCR2 treatment for arthritis strikes out.
    Cho Y and Lolis E. Arthritis Rheum. (2011) 63(1):23-5.
Education
Ph.D., 1962, Fordham University
Research Interests
Opioid receptors are the targets of narcotics such as morphine and heroin. The long-range goal of our research is focused on how opioids affect brain development.
Recent Publications
  • Morphine modulation of thrombospondin levels in astocytes and its implications for neurite outgrowth and synapse formation.
    Ikeda H, Myatake M, et al. J Biol Chem. (2010) 285(49):38415-27.
  • Mu and kappa opioids modulate mouse embryonic stem cell-derived neural progenitor differentiation via MAP kinases.
    Hahn JW, Jagwani S, Kim E, et al. J Neurochem. (2010) 112(6):1431-41.
Education
M.D., 1985, Catholic University School of Medicine, Rome, Italy.
Research Interests
We are interested in the structure and function of trypsin-like proteases, especially in the molecular determinants of substrate specificity and allosteric regulation. Our main focus is on thrombin, the key enzyme of blood coagulation and the prototypic allosteric protease. Our experimental approaches encompass enzyme kinetics (steady state and pre-steady state), thermodynamics (calorimetry), site-directed mutagenesis, protein engineering and X-ray structural biology. Our theoretical approaches involve linkage, allostery and site-specific thermodynamics.
Recent Publications
  • Autoactivation of thrombin precursors.
    Pozzi N, Chen Z, et al. J Biol Chem. (2013) 288(16):11601-10.
  • Conformational selection or induced fit? A critical appraisal of the kinetic mechanism.
    Vogt AD and Di Cera E. Biochemistry. (2012) 51(30):5894-902.
  • Conformational selection in trypsin-like proteases.
    Pozzi N, Vogt AD, et al. Curr Opin Struct Biol. (2012) 22(4):421-31.
  • Exposure of R169 controls protein C activation and auto activation.
    Pozzi N, Barranco-Medina S, et al. Blood. (2012) 120(3):664-70.
  • Thrombomodulin is required for the antithrombotic activity of thrombin mutant W215A/E217A in a mouse model of arterial thrombosis.
    Vicente CP, et al. Thromb Res. (2012) 130(4):646-8.
Education
Ph.D., 1980, University of Tennessee Oakridge National Laboratory
Research Interests
We use Drosophila molecular genetics to understand how chromosome structure controls gene expression during development. Our studies have shed light on the molecular mechanisms of Cornelia de Lange syndrome, which causes diverse developmental deficits in humans.
Recent Publications
    li>Wap1 antagonizes cohesin binding and promotes Polycomb-group silencing in Drosophila.
    Cunningham MD, Gause M, et al. Development. (2012) 139(22):4172-9.
  • The Drosophila MI-2 chromatin-remodeling factor regulates higher-order chromatin structure and cohesin dynamics in vivo.
    Fasulo B, Deuring R, et al. PLoS Genet. (2012) 8(8):e1002878.
  • The ancient and evolving roles of cohesin in gene expression and DNA repair.
    Dorsett D, Strom L. Curr Biol. (2012) 22(7):R240-R250.
  • Cohesin selectively binds and regulates genes with paused RNA polymerase.
    Fay A, Misulovin Z, et al. Curr Biol. (2011) 21(19):1624-1634.
  • Cohesin: genomic insights into controlling gene transcription and development.
    Dorsett D. Curr Opin Gent Dev. (2011) 21(2):199-206.
Education
Ph.D., 1982, University of North Carolina, Chapel Hill
Research Interests
Research in my lab concerns four aspects of transcriptional regulation: histone biotinylation and gene expression; transcriptional activation and chromatin remodeling; RNA polymerase elongation factors and gene regulation; and heterochromatin and gene regulation. We use the fruit fly, Drosophila melanogaster, as a model to study mechanisms of gene activation and gene silencing.
Recent Publications
  • Telomeres, cancer & aging: Live long & prosper?
    Eissenberg JC. Mo Med. (2013) 110(1):11-6.
  • The unique GGA clathrin adaptor of Drosophila melanogaster is not essential.
    Luan S, Ilvarsonn AM, Eissenberg JC. PLoS ONE. (2012) 7(9):e45163.
  • Structural biology of the chromodomain: Form and function.
    Eissenberg JC. Gene. (2012) 496(2):69-78.
  • The little elongation complex (LEC) regulates small nuclear RNA transcription.
    Smith ER, Lin C, Garrett AS, Thornton J, Mohaghegh N, Jackson J, Saraf A, Swanson SK, Seidel C, Florens L, Washburn MP, Eissenberg JC, Shilatifard A. Mol Cell. (2011), 44:954-965.
  • The role of MOF in the ionizing radiation response is conserved in Drosophila melanogaster.
    Bhadra MP, Horikoshi N, Pushpavallipvalli SNCVL, Sarkar A, Bag I, Krishan A, Lucchesi JC, Kumar R, Yang Q, Pandita RK, Singh M, Bhadra U, Eissenberg JC, Pandita TK. Chromosoma. (2012) 121(1):79-90.
Education
Ph.D., 1985, University of Missouri-Columbia
Research Interests
We are interested in biochemical mechanisms responsible for the pathophysiological sequelae of cardiovascular diseases including ischemic heart disease and atherosclerosis. Areas of research focus on enzymic and free radical targeting of membrane phospholipids, alterations in lipid metabolism, and alterations in signaling pathways as mechanisms involved in cardiovascular diseases. We combine our expertise using physiological models of disease coupled with expertise in mass spectrometry and bioorganic techniques to reveal new mechanistic insights into cardiovascular disease.
Recent Publications
  • Obesity-related alterations in cardiac lipid profile and nondipping blood pressure pattern during transition to diastolic dysfunction in male db/db mice.
    Demarco VG, Ford DA, et al. Endocrinology. (2013) 154(1):159-71.
  • Cholesterol efflux analyses using stable isotopes and mass spectrometry.
    Brown RJ, Shao F, et al. Anal Biochem. (2012) 433(1):56-64.
  • Dietary trans-fatty acid induced NASH is normalized fFollowing loss of trans-fatty acids from hepatic lipid pools.
    Neuschwander-Tetri BA, Ford DA, et al. Lipids. (2012) 47(10):941-50.
  • miR-33 controls the expression of biliary transporters, and mediates statin- and diet-induced hepatotoxicity.
    Allen RM, Marquart TJ, et al. EMBO Mol Med. (2012) 4(9):882-95.
  • Strategies for the analyses of chlorinated lipids in biological systems.
    Wacker BK, Albert CJ, et al. Free Radic Biol Med. (2012) Jun 17 [Epub ahead of print].
  • MALDI mass spectrometric imaging of cardiac tissue following myocardial infarction in a rat coronary artery ligation model.
    Menger RF, Stutts WL, et al. Anal Chem. (2012) 84(2):1117-25.
  • Electrospray ionization tandem mass spectrometry of sodiated adducts of cholesterol esters.
    Bowden JA, Shao F, et al. Lipids. (2011) 46(12):1169-79.
  • Analysis of cholesteryl esters and diacylglycerols using lithiated adducts and electrospray ionization-tandem mass spectrometry.
    Bowden JA, Albert CJ, et al. Anal Biochem. (2011) 417(2):202-10.
  • Lipid oxidation by hypochlorous acid: Chlorinated lipids in atherosclerosis and myocardial ischemia.
    Ford DA. Clin Lipidol. (2011) 5(6):835-52.
  • An examination of pentafluorobenzoyl derivatization strategies for the analysis of fatty alcohols using gas chromatography/electron capture negative ion chemical ionization-mass spectrometry.
    Bowden JA, Ford DA. J Chromatogr B Analyt Technol Biomed Life Sci. (2011) 879(17-18):1375-83.
Education
Ph.D., Washington University School of Medicine
Research Interests
Alterations in the DNA damage response pathway, DNA repair mechanisms, and telomere biology are among the leading causes of genomic instability in aging and cancer. Our long term goal is to identify novel molecular pathways contributing to genomic instability, which can be used as therapeutic targets. We have focused on understanding how alterations in nuclear structural proteins –lamins- and chromatin structure -epigenetic changes- impact on DNA repair and telomere biology. Our studies revealed new pathways important in diseases such as laminopathies and cancer that are being tested as potential biomarkers for diagnosis, prognosis, and customization of treatment.
Recent Publications
  • BRCA1 loss activates cathepsin L-mediated degradation of 53BP1 in breast cancer cells.
    Grotsky DA, Gonzalez-Suarez I, et al. J Cell Biol. (2013) 200(2):187-202.
  • Regulating the levels of key factors in cell cycle and DNA repair: new pathways revealed by lamins.
    Redwood AB, Gonzalez-Suarez I and Gonzalo S. Cell Cycle. (2011) 10(21):3652-7.
  • A dual role for A-type lamins in DNA double-strand breaks repair.
    Redwood AB, Perkins SM, Vanderwaal RP, Feng Z, Biehl KJ, Gonzalez-Suarez I, Morgado-Palacin L, Shi W, Sage J, Roti-Roti JL, Stewart CL, Zhang J and Gonzalo S. Cell Cycle. (2011) 10(15):2549-60.
  • A new pathway that regulates 53BP1 stability implicates Cathepsin L and Vitamin D in DNA repair.
    Gonzalez-Suarez I, Redwood AB, Grotsky DA, Neumann M, Cheng E, Stewart CL, Dusso A and Gonzalo S. EMBO J. (2011) 30(16):3383-96.
  • The mTOR inhibitor Rapamycin suppresses DNA souble-strand break repair.
    Chen H, Ma Z, Vanderwaal RP, Feng Z, Gonzalez-Suarez I, Wang S, Zhang J, Roti Roti JL, Gonzalo S and Zhang J. Radiat Res. (2011) 175(2):214-24.
Positions
A Postdoctoral/Scientist/Technician position is available in the laboratory beginning immediately. Candidates should have experience in mouse models of tumorigenesis. The project will focus on preclinical studies that test the importance of a novel pathway for diagnosis, prognosis, and customization of breast cancer treatment. Interested candidates should submit a curriculum vitae (which lists at least 2 referees) and a brief letter outlining prior research experience via e-mail to sgonzalo@slu.edu.
Education
Ph.D., 1986, Technical University of Wroclaw, Poland
Research Interests
Our lab has two major research interests: mechanisms of transcription regulation and development of novel sensors for biomolecule detection and imaging. Our interest in transcription regulation is to understand the mechanism of transcription initiation by bacterial and archaeal RNA polymerases. Our primary focus in sensor research is to develop robust highly specific and sensitive molecular sensors that could be utilized in research, medical diagnosis and pathogen detection.
Recent Publications
  • Detection methodology based on target molecule-induced sequence-specific binding to a single-stranded oligonucleotide.
    Lass-Napiorkowska A, Heyduk E, et al. Anal Chem. (2012) 84(7):3382-3389. PubMed PMID: 22401560
  • Promoter spacer DNA plays an active role in integrating the functional consequences of RNA polymerase contacts with -10 and -35 promoter elements.
    Sztiller-Sikorska M, Heyduk E, and Heyduk T. Biophys Chem. (2011) 159(1):73-81. PubMed PMID: 21621902
Education
Ph.D., 1972, National Taiwan University
Research Interests
The areas of research in this laboratory are: 1) autocrine transformation by the v-sis/c-sis oncogene and novel trans-Golgi network (TGN) signal transduction, and 2) role of the transforming growth factor ß (TGF-ß) type V receptor (TR-V) in the biological functions of TGF-ß.
Recent Publications
  • CRSBP-1/LYVE-1 ligands stimulate contraction of the CRSBP-1 associated ER network in lymphatic endothelial cells.
    Hou WH, Liua IH, et al. FEBS Lett. (2012) 586(10):1480-7.
  • CRSBP-1/LYVE-1 ligands disrupt lymphatic intercellular adhesion by inducing tyrosine phosphorylation and internalization of VE-cadherin.
    Hou WH, Liua IH, et al. J Cell Sci. (2011) 124(Pt 8):1231-44.
  • A mechanism by which dietary trans fats cause atherosclerosis.
    Chen CL, Tetri LH, et al. J Nutr Biochem. (2011) 22(7):649-55.
Education
Ph.D., 1972, University of California, San Francisco
Research Interests
The primary goal of this research is to develop a new chemotherapeutic option for the treatment of cancer. We have chosen to develop Zn as a chemotherapeutic agent, based on our observations that Zn treatment of a variety of cancer cell lines results cell death. The rapidity with which cell death is induced is very attractive with respect to treatment protocols and is in dramatic contrast to the days-weeks required to achieve cell death with current chemotherapeutics. Importantly, Zn-mediated cell death is independent of the presence or absence of growth factors, is not limited to rapidly growing cells, and is independent of p53 status.
Recent Publications
  • Zinc is a potential therapeutic for chemoresistant ovarian cancer.
    Bastow M, Kriedt CL, et al. J Exp Ther Oncol. (2011) 9(3):175-181.
  • Zinc functions as a cytotoxic agent for prostate cancer cells independent of culture and growth conditions.
    Kriedt CL, Baldassare J, et al. J Exp Ther Oncol. (2010) 8:287-295.
Education
Ph.D., 1993 Engelhardt Institute of Biochemistry and Molecular Biology, Moscow, Russian Academy of Sciences
Research Interests
Our lab studies the mechanism of protein function at the atomic resolution level utilizing X-ray crystallography and biochemical approaches. The main focus is recombination mediator proteins (RMPs), which are essential for genome stability and DNA repair in all organisms.
Recent Publications
  • A dual role for mycobacterial RecO in RecA-dependent homologous recombination and RecA-independent single-strand annealing.Ryzhikov M, et al. Nucleic Acids Res. (2013) 41(4):2284-95.
  • Structural studies of SSB iInteraction with RecO.
    Ryzhikov M and Korolev S. Methods Mol Biol. (2012) 922:123-31.
  • Plasmodium falciparum SSB tetramer wraps single-stranded DNA with similar topology but opposite polarity to E. coli SSB.
    Antony E, Weiland EA, et al. J Mol Biol. (2012) 420(4-5):269-83.
  • SSB functions as a sliding platform that migrates on DNA via reptation.
    Zhou R, Kozlov AG, et al. Cell. (2011) 146(2):222-32.
  • Rotations of the 2B sub-domain of E. coli UvrD helicase/translocase coupled to nucleotide and DNA binding.
    Jia H, Korolev S, et al. J Mol Biol. (2011) 411(3):633-48.
  • Mechanism of RecO recruitment to DNA by single-stranded DNA binding protein.
    Ryzhikov M, Postnov D, et al. Nucleic Acids Res. (2011) 39(14):6305-14.
  • The loop-less tmCdc34 E2 mutant defectie in polyubiquitination in vitro and in vivo supports yeast growth in a manner dependent on Ubp14 and Cka2.
    Lass A, Cocklin R, et al. Cell Div. (2011) 6(1):7.
Education
Ph.D., 1989, Boston University
Research Interests
Our research is primarily focused on understanding the mechanism by which coagulation proteases interact with their target cofactors, substrates, and inhibitors, and how heparin enhances the inhibitory function of antithrombin in the regulation of the proteolytic activities of these proteases. Another project in the lab focuses on understanding the mechanism by which coagulation proteases interact with endothelial cell surface receptors to elicit diverse intracellular signaling responses. We employ biophysical, biochemical, and molecular biological approaches to study these questions.
Recent Publications
  • Transmitting the allosteric signal in methylglyoxal synthase.
    Falahati H, Pazhang M, et al. Protein Eng Des Sel. (2013) Apr 16 [Epub ahead of print].
  • Antithrombin is protective against myocardial ischemia and reperfusion injury.
    Wang J, Wang Y, et al. J Thromb Haemost. (2013) Apr 13 [Epub ahead of print].
  • Residues of the 39-loop restrict the plasma inhibitor specificity of factor IXa.
    Yang L and Rezaie AR. J Biol Chem. (2013) 288(18):12692-8.
  • Variable contributions of basic residues forming an APC exosite in the binding and inactivation of factor VIIIa.
    Takeyama M, Wintermute JM, et al. Biochemistry. (2013) 52(13):2228-35.
  • Expression and functional characterization of natural R147W and K150del variants of protein C in the Chinese population.
    Ding Q, Yang L, et al. Thromb Haemost. (2013) 109(4):614-24.
  • Phosphatidylserine-induced Factor Xa dimerization and binding to Factor Va are competing processes in solution.
    Majumder R, Koklic T, et al. Biochemistry. (2013) 52(1):143-51.
  • Contribution of the NH2-terminal EGF-domain of factor IXa to the specificity of intrinsic tenase.
    Qureshi SH, Yang L, Rezaie AR. Thromb Haemost. (2012) 108(6):1154-64.
  • Activated protein C modulates cardiac metabolism and augments autophagy in the ischemic heart.
    Costa R, Morrison A, et al. J Thromb Haemost. (2012) 10(9):1736-445.
  • Characterization of the heparin-binding site of the protein z-dependent protease inhibitor.
    Yang L, Ding Q, et al. Biochemistry. (2012) 51(19):4078-85.
  • Identification of exosite residues of factor Xa involved in recognition of PAR-2 on endothelial cells.
    Manithody C, Yang L, et al. Biochemistry. (2012) 51(12):2551-7.
  • Polyphosphate elicits pro-inflammatory responses that are counteracted by activated protein C in both cellular and animal models.
    Bae JS, Lee W, et al. J Thromb Haemost. (2012) 10(6):1145-51.
  • Determinants of the specificity of protease-activated receptors 1 and 2 signaling by factor Xa and thrombin.
    Rana S, Yang L, et al. J Cell Biochem. (2012) 113(3):977-84.
Education
M.D., 1981, Ph.D., 1984, University of Illinois at Urbana-Champaign
Research Interests
Our clinical activities include screening for inborn errors of metabolism in children by quantifying chemicals in body fluids by gas chromatography-mass spectrometry. We developed a new method of sample preparation which allows carbohydrates and amino and organic acids to be detected in the same sample. Our current research is concerned with the evaluation of special nutritional needs in children with Down syndrome and the diagnosis of vitamin deficiency by quantitation of urinary metabolites after an oral dose of amino acids and other food constituents.
Recent Publications
  • Targeted mutagenesis of mitochondrial carbonic anhydrases VA and VB implicates both enzymes in ammonia detoxification and glucose metabolism.
    Shah GN, Rubbelke TS, et al. Proc Natl Acad Sci USA. (2013) 110(18):7423-8.
  • Substrate oxidation and cardiac performance during exercise in disorders of long chain fatty acid oxidation.
    Behrend AM, Harding CO, et al. Mol Genet Metab. (2012) 105(1):110-5.
  • One-step metabolomics: carbohydrates, organic and amino acids quantified in a single procedure.
    Shoemaker JD. J Vis Exp. (2010) 25(40).
  • Isocitrate dehydrogenase is important for nitrosative stress resistance in Cryptococcus neoformans, but oxidative stress resistance is not dependent on glucose-6-phosphate dehydrogenase.
    Brown SM, Udaphya R, et al. Eukaryot Cell. (2010) 9(6):971.
  • Diethylene glycol in propofol infusion syndrome?
    Shoemaker JD. Drug Saf. (2010) 33(1):81.
Education
Ph.D., 1991, University of Gdansk, Poland
Research Interests
We are broadly interested in the role, function and regulation of the ubiquitin-proteasome system. Our former projects focused on the mechanism by which proteins are recruited for degradation by the 26S proteasome in yeast. We have recently initiated three new research directions that focus on the role of proteasomal proteolysis in 1) autoimmune diseases (type 1 diabetes); 2) protein misfolding diseases (liver disease associated with alpha 1 antitrypsin deficiency); and early antiviral responses (ectromelia virus/primary mouse macrophages). Biochemical and cellular approaches are our primary research tools.
Recent Publications
  • Early Immunoproteasome Activation in Mouse Pancreatic β-cells by IFNβ: New Insights into Auto-antigen Generation in Type I Diabetes?
    Freudenburg W, Gautam M, Chakraborty P, James J, Richards J, et al. J Clin Cell Immunol. (2013) 3:141.
  • Reduction in ATP levels triggers immunoproteasome activation by the 11S (PA28) regulator during early antiviral response mediated by IFNbeta in mouse pancreatic beta-cells.
    Freudenburg W, Gautam M, Chakraborty P, Richards J, Salvatori A, Baldwin A, Schriewer J, Buller M, Corbett J, Skowyra D. PLOS One. (2013) 8(2):e52408.
  • The loop-less tmCdc34 E2 mutant defective in polyubiquitination in vitro and in vivo supports yeast growth in a manner dependent on Ubp14 and Cka2.
    Lass A, Cocklin R, Scaglione KM, Skowyra M, Korolev S, Goebl M, Skowyra D. Cell Div. (2011) 6(1):7.

Full list of publications in PubMed: Skowyra D
Freudenburg W, Gautam M, Chakraborty P, James J, Richards J, et al. (2013) Early Immunoproteasome Activation in Mouse Pancreatic β-cells by IFNβ: New Insights into Auto-antigen Generation in Type I Diabetes? J Clin Cell Immunol 3: 141. doi:10.4172/2155-9899.1000141
Education
M.D., 1957, Saint Louis University
Research Interests
Areas of research include: (i) experimental approaches to treatment of murine beta-glucuronidase deficiency mucopolysaccharidosis (Sly syndrome), (ii) biochemical and molecular genetics of human deficiencies of beta-glucuronidase and carbonic anhydrases, and (iii) developing transgenic mice and mouse models of human disease by targeted mutagenesis.
Recent Publications
  • Targeted mutagenesis of mitochondrial carbonic anhydrases VA and VB implicates both enzymes in ammonia detoxification and glucose metabolism.
    Shah GN, Rubbelke TS, et al. Proc Natl Acad Sci USA. (2013) 110(18):7423-8.
  • GPI-anchored carbonic anhydrase IV displays both intra-and extracellular activity in cRNA-injected oocytes and in mouse neurons.
    Schneider HP, Alt MD, et al. Proc Natl Acad Sci USA. (2013) 110(4):1494-9.
  • NMDA receptor-dependent afterdepolarizations are curtailed by carbonic anhdrase 14: Regulation of a short-erm postsynaptic potentiation.
    Makani S, Chen HY, et al. J Neurosci. (2012) 32(47):16754-62.
  • Carbonic anhydrase IX in malignant pleural mesotheliomas: A potential target for anti-cancer therapy.
    Kivela AJ, Knuuttila A, et al. Bioorg Med Chem. (2012) 21(6):1483-8.
  • Biochemical evidence for superior correction of neuronal storage by chemically modified enzyme in murine mucopolysaccharidosis VII.
    Huynh HT, Grubb JH, et al. Proc Natl Acad Sci USA. (2012) 109(42):17022-7.
  • Assessment of bone dysplasia by micro-CT and glycosaminoglycan levels in mouse models for mucopolysaccharidosis type I, IIIA, IVA, and VII.
    Rowan DJ, Tomatsu S, et al. J Inherit Metab Dis. (2012) 36(2):235-46.
  • Long circulating enzyme replacement therapy rescues bone pathology in mucopolysaccharidosis VII murine model.
    Rowan DJ, Tomatsu S, et al. Mol Genet Metab. (2012) 107(1-2):161-72.
  • Effect of sulfonamides as carbonic anhydrase VA and VB inhibitors on mitochondrial metabolic energy conversion.
    Arechederra RL, Waheed A, et al. Bioorg Med Chem. (2012) 21(6):1544-8.
  • Structure, function and applications of carbonic anhydrase isozymes.
    Imtaiyaz Hassan M, Shajee B, et al. Bioorg Med Chem. (2012) Apr 27 [Epub ahead of print].
  • Carbonic anhydrase IX promotes tumor growth and necrosis in vivo and inhibition enhances anti-VEGF therapy.
    McIntyre A, Patiar S, et al. Clin Cancer Res. (2012) 18(11):3100-11.
  • Carbonic anydrase isozymes II, IX, and IXX in uterine tumors.
    Hynninen P, Parkkila S, et al. APMIS. (2012) 120(2):117-29.
Education
Ph.D., 1995, University of Padua, Italy
Research Interests
Aberrant DNA replication is one of the leading causes of mutations and chromosome rearrangements associated with several cancer related pathologies, and several chemotherapeutic strategies employ agents that induce replication stress in the attempt to selectively target highly proliferating cancer cells. Our group studies the mechanisms that operate in eukaryotic cells to maintain replication fork integrity. In particular, we use a combination of cellular, biochemical and structural approaches to define the role of RecQ helicases in this process. Our recent studies provided new mechanistic insight into the role of RecQ helicases in replication stress response, offering new molecular perspectives to potentiate chemotherapeutic regimens based on replication inhibitor treatment.
Recent Publications
  • Bioinformatic analysis of RecQ4 helicases reveals the presence of a RQC domain and a Zn knuckle.
    Marino F, Vindigni A, et al. Biophys Chem. (2013) 177-178:34-9.
  • Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase 1 inhibition.
    Berti M, Chaudhuri AR, et al. Nat Struct Mol Biol. (2013) Feb 10 [Epub ahead of print].
  • In vitro enzyme comparative kinetics: Unwinding of surface-bound DNA nanostructures by RecQ and RecQ1.
    Parisse P, Vindigni A, et al. J Phys Chem Lett. (2012) 3(23):3532-7.
  • The alpha2 helix in the DNA ligase IV BRCT-1 domain is required for targeted degradation of ligase IV during adenovirus infection.
    Gilson T, Greer AE, et al. Virology. (2012) 428(2):128-35.
  • Proteomic analysis of gastric cancer and immunoblot validation of potential biomarkers.
    Kocevar N, Odreman F, et al. World J Gastroenterol. (2012) 18(11):128-35.
  • The human RECQ1 helicase is highly expressed in glioblastoma and plays an important role in tumor cell proliferation.
    Mendoza-Maldonado R, Faoro V, et al. Mol Cancer. (2011) 10:83-100.
  • A prominent {beta}-hairpin structure in the winged-helix domain of RECQ1 is required for DNA unwinding and oligomer formation.
    Lucic B, Zhang Y, et al. Nucleic Acids Res. (2011) 39(5):1703-17.

Full list of publications in PubMed: Vindigni A
Education
Ph.D., 2006, University of Wisconsin-Madison
Research Interests
Few biochemical reactions are as critical for life as translation. We are interested in understanding the functional consequences of arrested translation (or "ribosome stalling") for controlling gene expression and protein biogenesis using genome-wide proteomics, next-generation sequencing, bacterial genetics and biochemistry. We also aim to investigate the selectivity and resistance properties of antibiotics that target the ribosome tunnel. This work will help in the development of more effective antimicrobial drugs.
Recent Publications
  • Mutations in the ribosomal protein L22 selectively suppress the expression of a secreted bacterial virulence factor.
    Yap MN and Bernstein HD. J Bacteriol. (2013) Apr 26 [Epub ahead of print].
  • The translational regulatory function of SecM requires a novel mode of membrane targeting.
    Yap MN and Bernstein HD. Mol Microbiol. (2011) 81(2):540-53.
  • Genome sequence of the plant-pathogenic bacterium Dickeya dadantii 3937.
    Glasner JD, Yang CH, et al. J Bacteriol. (2011) 193(8):2076-7.
  • The plasticity of a translation arrest motif yields insights into nascent polypeptide recognition inside the ribosome tunnel.
    Yap MN and Berstein HD. Mol Cell. (2009) 34(2):201-11.