Edward A. Doisy Department of
Biochemistry and Molecular Biology

Primary Faculty

Education
Ph.D., 2001, Washington University in St. Louis
Research Interests
The regulation of pre-mRNA processing, critical in the control of gene function and often linked to human disease, is mediated through the interaction between mRNA and protein partners. The TAR DNA binding protein (TDP-43) is an essential RNA binding protein whose dysfunction and aggregation are tightly associated with neurodegenerative disorders, i.e., amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, and frontotemporal dementia (FTLD). We investigate the cellular function and molecular structure of RNA binding proteins, such as TDP-43, to understand basic mechanisms of RNA processing and pathogenesis.
Recent Publications
  • TDP-43 regulates its mRNA levels through a negative feedback loop.
    Ayala YM, DeConti L, et al. (2011) EMBO J. 30:277-88.
  • Structural determinants of the cellular localization and shuttling of TDP-43.
    Ayala YM, Zago P, et al. J Cell Sci. (2008) 121:3778-85.
  • TDP-43 regulates pRB phosphorylation through the repression of CDK6 expression.
    Ayala YM, Misteli T and Baralle FE. Proc Natl Acad Sci USA. (2008) 105:3785-89.

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
  • Long-term therapeutic silencing of miR-33 increases circulating triglyceride levels and hepatic lipid accumulation in mice.
    Goedeke L, Salerno A, et al. EMBO Mol Med. (2014) 6(9):1133-1141.
  • Perilipin-5 is regulated by statins and controls triglyceride contents in the hepatocyte.
    Langhi C, Marquart TJ, et al. J Hepatol. (2014) 61(2):358-365.
  • Control of very low-denisty lipoprotein secretion by N-ethylmaleimide-sensitive factor and miR-33.
    Allen RM, Marquart TJ, et al. Circ Res. (2014) 115(1):10-22.
  • MicroRNAs and cardiovascular disease.
    Fernandez-Hernando C, Baldán A. Curr Genet Med Rep. (2013) 1(1):30-380.
  • Quest for new biomarkers in atherosclerosis.
    Cho Y, Baldán A. Mo Med. (2013) 110(4):325-330.
  • Impaired liver regeneration in Ldlr-/- mice is associated with an altered hepatic profile of cytokines, growth factors and lipids.
    Pauta M, Rotllan N, et al. J Heptaol. (2013) 59(4):731-737.
  • 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) 112(12):1602-1612.
  • 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.
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
  • Protein O-GlcNAcylation.
    Tian L, Simmons G, Chang YH. JSM Biochem Mol Biol. (2013) 1(1):1005-7.
  • A pilot study of pepsin in tracheal and oral secretions.
    Challom M, Tricomi S, et al. Am J Crit Care. (2013) 22(5):408-11.
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. However, the molecular details 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
  • Quest for new biomarkers in atherosclerosis.
    Cho Y, Baldán A. Mo Med. (2013) 110(4):325-330.
  • Structural studies of small molecule inhibitors of MIF.
    Cho Y and Lolis E. The MIF handbook. (2012) World Scientific Publishing Co.
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
  • Acute and chronic mu opioids differentially regulate thrombospondins 1 and 2 isoforms in astrocytes.
    Phamduong E, Rathore MK, et al. ACS Chem. Neurosci. (2013) 5(2):106-114.
Education
M.D., 1985, Catholic University School of Medicine, Rome, Italy.
Research Interests
We study function and regulation of proteins involved in blood coagulation, the molecular mechanism of zymogen activation and auto-activation, and the rational engineering of protease specificity for therapeutic and biotechnological purposes. Also of interest is ligand binding theory and kinetics. Our approach utilizes rapid kinetics, thermodynamics, spectroscopy and x-ray crystallography.
Recent Publications
  • The linker connecting the two kringles plays a key role in prothrombin activation.
    Pozzi N, Chen Z, et al. Proc Natl Acad Sci USA. (2014) 111(21):7630-5.
  • Special issue on conformational selection.
    Di Cera E. Biophys. Chem. (2013) 186:1-2.
  • Histone h4 promotes prothrombin autoactivation.
    Barranco-Medina S, Pozzi N, et al. J. Biol. Chem. (2013) 288(50):35749-57.
  • Essential role of conformational selection in ligand binding.
    Vogt AD, Pozzi N, et al. Biophys Chem. (2013) 186:13-21.
  • In vitro veritas: 90 years of biochemistry at Saint Louis University.
    Eissenberg JC, Di Cera E. Mo Med. (2013) 110(4):297-301.
  • Conformational selection is a dominant mechanism of ligand binding.
    Vogt AD, Di Cera E. Biochemistry. (2013) 52(34):5723-9.
  • Crystal structure of prothrombin reveals conformational flexibility and mechanism of activation.
    Pozzi N, Chen Z, et al. J Biol Chem. (2013) 288(31):22734-44.
  • Autoactivation of thrombin precursors.
    Pozzi N, Chen Z, et al. J Biol Chem. (2013) 288(16):11601-10.
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
  • Checks and balances between cohesion and polycomb in gene silencing and transcription.
    Dorsett D, Kassis JA. Curr Biol. (2014) 24(11):R535-R539.
  • Sall1 balances self-renewal and differentiation of renal progenitor cells.
    Basta JM, Robbins L, et al. Development. (2014) 141(5):1047-1058.
  • Cornelia de Lang syndrome: Further delineation of phenotype, cohesion biology and educational focus, 5th Biennial Scientific and Educational Symposium abstracts.
    Kline AD, Calof AL, et al. Am J Med Genet A. (2014) 164A(6):1384-1393.
  • What fruit flies can tell us about human birth defects.
    Dorsett D. Mo Med. (2013) 110(4):309-313.
  • The Drosophila enhancer of split gene complex: Architecture and coordinate regulation by Notch, Cohesion, and Polycomb group proteins.
    Schaaf CA, Misulovin Z, et al. G3 (Bethesda). (2013) 3(10):1785-1794.
  • Cohesin and polycomb proteins functionally interact to control transcription at silenced and active genes.
    Schaaf CA, Misulovin Z, et al. PLoS Genet. (2013) 9(6):e1003560.
  • Genome-wide control of RNA polymerase II activity by cohesion.
    Schaaf CA, Kwak A, et al. PLoS Genet. (2013) 9(3):e1003382.
  • Cohesin at active genes: A unifying theme for cohesion and gene expression from model organisms to humans.
    Dorsett D, Merkenschlager M. Curr Opin Cell Biol. (2013) 25(3):327-333.
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
  • (2014) Histone H3 lysine-to-methionine mutants as a paradigm to study chromatin signaling.
    Herz, H-M, Morgan M, et al. Science. (2014) 345(6200):1065-1070.
  • HP1a: A structural chormosomal protein regulating transcription.
    Eissenberg JC, Elgin SC. Trends Genet. (2014) 30(3):103-110.
  • Polyphosphate amplifies proinflammatory responses of nuclear proteins through interaction with receptor for advanced glycation end products and P2Y1 purinergic receptor.
    Dinarvand P, Hassanian SM, et al. Blood. (2013) 123(6):935-945.
  • Seed and soil: A conceptual framework of metastasis for clinicians.
    Faraji F, Eissenberg JC. Mo Med. (2013) 110(4):302-308.
  • In vitro veritas: 90 years of biochemistry at Saint Louis University.
    Eissenberg JC, Di Cera E. Mo Med. (2013) 110(4):297-301.
  • The little elongation complex functions at initiation and elongation phases of snRNA gene transcription.
    Hu D, Smith ER, et al. Mol Cell. (2013) 51(4):493-505.
  • Telomeres, cancer & aging: Live long & prosper?
    Eissenberg JC. Mo Med. (2013) 110(1):11-6.
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
  • Oxidation of plasmalogens, low-density lipoprotein and RAW 264.7 cells by photoactivatable atomic oxygen precursors.
    Bourdillon MT, Ford DA, et al. Photochem Photobiol. (2014), in press.
  • Inhibiting monoacylglycerol acyltransferase 1 ameliorates hepatic metabolic abnormalities, but not inflammation and injury in mice.
    Soufi N, Hall AM, et al. J Biol Chem. (2014) Sept 11 [Epub ahead of print].
  • Lipidomic analyses of female mice lacking hepatic lipase and endothelial lipase indicate selective modulation of plasma lipid species.
    Yang Y, Kuwano T, et al. Lipids. (2014) 49(6):505-515.
  • Elaidic acid increases hepatic lipogenesis by mediating sterol regulatory element binding protein-1c activity in HuH-7 cells.
    Shao F, Ford DA. Lipids. (2014) 49(5):403-413.
  • Alpha-chlorofatty acid accumulates in activated monocytes and causes apoptosis through reactive oxygen species production and endoplasmic reticulum stress.
    Wang WY, Albert CJ, et al. Arterioscler Thromb Vasc Biol (2014) 34(3):526-532.
  • Dietary omega-3 polyunsaturated fatty acids alter the fatty acid composition of hepatic and plasma bioactive lipids in C57BL/6 mice: A lipidomic approach.
    Balogun KA, Albert CJ, et al. PLoS One. (2013) 8(11):e82399.
  • LXRs regulate ER stress and inflammation through dynamic modulation of membrane phospholipid composition.
    Rong X, Albert CJ, et al. Cell Metab. (2013) 18(5):685-97.
  • Long-term expression of apolipoprotein B mRNA-specific hammerhead ribozymes via scAAV8.2 vector inhibit atherosclerosis in mice.
    Nischal H, Sun H, et al. Mol Ther Nucleic Acids. (2013) 2:e125.
  • Approaches for the analysis of chlorinated lipids.
    Wang W, Albert CJ, and Ford DA. Anal Biochem. (2013) 443(2):148-52.
  • Differential regulation of ABCA1 and macrophage cholesterol efflux by elaidic and oleic acids.
    Shao F and Ford DA. Lipids. (2013) 48(8):757-67.
  • Hydrolysis products generated by lipoprotein lipase and endothelial lipase differentially impact THP-1 macrophage cell signaling pathways.
    Essaji Y, Yang Y, et al. Lipids. (2013) 48(8):769-78.
  • Impaired liver regeneration in Ldlr -/- mice is associated with an altered hepatic profile of cytokines, growth factors, and lipids.
    Pauta M, Rotllan N, et al. J Hepatol. (2013) 59(4):731-7.
  • Absence of myocardial calcium-independent phospholipase A2γ results in impaired PGE2 production and decreased survival in mice with acute Trypanosoma cruzi infection.
    Sharma J, Eickhoff CS, et al. Infect Immun. (2013) 81(7):2278-87.
  • Acyl-CoA synthetase 1 is induced by gram-negative bacteria and lipopolysaccharide and is required for phospholipid turnover in stimulated macrophages.
    Rubinow KB, Wall VZ, et al. J Biol Chem. (2013) 288(14):9957-70.
  • 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.
Education
Ph.D., Washington University School of Medicine
Research Interests
The human genome is organized into different levels of complexity. Packaging of DNA into different chromatin states and 3D nuclear organization of the genome are emerging as additional levels of regulation of genome function. Our broad research interests are to understand how alterations of nuclear architecture, chromatin structure, and genome stability contribute to the processes of aging and cancer. Our studies revealed that the structural nuclear proteins A-type lamins play a key role in the maintenance of telomere structure, length and function, as well as mechanisms of DNA double-strand break repair. Specifically, loss of A-type lamins increases the levels of the protease cathepsin L and its entry into the nucleus, which in turn leads to degradation of proteins with important roles in cell cycle regulation -Rb family members- and DNA repair -53BP1-. Loss of A-type lamins also leads to repression of BRCA1 and RAD51 genes, critical factors in homologous recombination. Interestingly, inhibition of cathepsin L activity with vitamin D or specific inhibitors rescues some of the phenotypes of lamins-deficient cells, providing new therapeutic possibilities. Most recently, we found that these novel pathways are also activated in BRCA1-deficient cells and subsets of breast cancer patients. Our current work aims to characterize in detail how these pathways contribute to the pathophysiology of cancer, aging, and laminopathies with the ultimate goal of using them as potential biomarkers for diagnosis, prognosis, and customization of treatment.
Recent Publications
  • DNA damage and lamins.
    Gonzalo S. Adv Exp Med Biol. (2014) 773:377-399.
  • Lamin A Δexon9 mutation leads to telomere and chromatin defects but not genomic instability.
    Das A, Grotsky DA, et al. Nucleus. (2013) 4(5):410-419.
  • Differences in 53BP1 and BRCA1 regulation between cycling and non-cycling cells.
    Croke M, Neumann MA, et al. Cell Cycle. (2013) 12(23):3629-39.
  • Novel roles of 1α,25(OH)2D3 on DNA repair provide new strategies for breast cancer treatment.
    Gonzalo S. J Steroid Biochem Mol Biol. (2013) 144PA:59-64.
  • The two faces of DNA repair: disease and therapy.
    Vindigni A, Gonzalo S. Mo Med. (2013) 110(4):314-319.
  • 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.
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
  • Ribosome display enhanced by next generation sequencing: A tool to identify antibody-specific peptide ligands.
    Heyduk T and Heyduk E. Anal Biochem. (2014) 464:73-82. PubMed PMID: 25058925
  • Kinetics of promoter escape by bacterial RNA polymerase: effects of promoter contacts and transcription bubble collapse.
    Ko J, Heyduk T. Biochem J. (2014) 463(1):135-144. PubMed PMID: 24995916
  • Next generation sequencing-based parallel analysis of melting kinetics of 4096 variants of a bacterial promoter.
    Heyduk E, Heyduk T. Biochemistry. (2014) 53(2):282-292. PubMed PMID: 24359527
  • Crystal structure of prothrombin reveals conformational flexibility and mechanism of activation.
    Pozzi N, Chen Z, et al. J Biol Chem. (2013) 288(31):22734-22744. PubMed PMID: 2377508
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.
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
  • RecO initiates DNA recombination and strand annealing through two alternative DNA-binding mechanisms.
    Ryzhikov M, Gupta R, et al. J Biol Chem. (2014) Aug 28 [Epub ahead of print].
  • Rous sarcoma virus synaptic complex capable of concerted integration is kinetically trapped by human immunodeficiency virus integrase strand transfer inhibitors.
    Pandey KK, Bera S, et al. J Biol Chem. (2014) 289(28):19648-58.
  • High resolution crystal structure of human beta-glucuronidase reveals structural basis of lysosome targeting.
    Hassan MI, Waheed A, et al. PLoS One. (2013) 8(11):e79687.
  • A dual role for mycobacterial RecO in RecA-dependent homologous recombination and RecA-independent single-strand annealing.
    Gupta R, Ryzhikov M, et al. Nucleic Acids Res. (2013) 41(4):2284-95.
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
  • Antithrombin up-regulates AMP-activated protein kinase signalling during myocardial ischaemia/reperfusion injury.
    Ma Y, Wang J, et al. Thromb Haemost. (2014) Sept 18, 113(1) [Epub ahead of print].
  • Molecular basis of the clotting defect in a bleeding patient missing the Asp-185 codon in the factor X gene.
    Lu Q, Yang L, et al. Thromb Res. (2014) Aug 20 [Epub ahead of print].
  • Protease-activated receptor signalling by coagulation proteases in endothelial cells.
    Rezaie AR. Thromb Haemost. (2014) Jul 3, 112(4) [Epub ahead of print].
  • Characterization of the protein Z-dependent protease inhibitor interactive-sites of protein Z.
    Qureshi SH, Lu Q, et al. Biochim Biophys Acta. (2014) Jun 21 [Epub ahead of print].
  • Engineering D-helix of antithrombin in alpha-1-proteinase inhibitor confers anti-inflammatory properties on the chimeric serpin.
    Yang L, Dinarvand P, et al. Thromb Haemost. (2014) 112(1):164-75.
  • Adenosine regulates the pro inflammatory signaling function of thrombin in endothelial cells.
    Hassanian SM, Dinarvand P, Rezaie AR. J Cell Physiol. (2014) 229(9):1292-300.
  • Thrombomodulin modulates cell migration in human melanoma cell lines.
    de Oliveira Ada S, Yang L, et al. Melanoma Res. (2014) 24(1):11-9.
  • Polyphosphate amplifies proinflammatory responses of nuclear proteins through interaction with receptor for advanced glycation end products and P2Y1 purinergic receptor.
    Dinarvand P, Hassanian SM, et al. Blood. (2013) 123(6):935-45.
  • Thrombin inhibits HMGB1-mediated proinflammatory signaling responses when endothelial protein C receptor is occupied by its natural ligand.
    Bae JS, Rezaie AR. BMB Rep. (2013) 46(11):544-9.
  • The missense Thr211Pro mutation in the factor X activation peptide of a bleeding patient causes molecular defect in the clotting cascade.
    Ding Q, Shen Y, et al. Thromb Haemost. (2013) 110(1):53-61.
  • Transmitting the allosteric signal in methylglyoxal synthase.
    Falahati H, Pazhang M, et al. Protein Eng Des Sel. (2013) 26(7):445-52.
  • Antithrombin is protective against myocardial ischemia and reperfusion injury.
    Wang J, Wang Y, et al. J Thromb Haemost. (2013) 11(6):1020-8.
  • 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.
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.
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
  • PiZ mouse liver accumulates polyubiquitin conjugates that associate with catalytically active 26S proteasomes.
    Haddock CJ, Blomenkamp K, Gautam M, James J, Mielcarska J, Gogol E, Teckman J, Skowyra D. PLoS One. (2014) 9(9):e106371.
  • Broad utility of an affinity-enrichment strategy for unanchored polyubiquitin chains.
    Strachan J, Shaw B, Tooth D, Krishna VG, de Pozo JC, Hill K, Bennett M, Gautam M, Skowyra D, Jacobson AD, Liu CW, Oldham N, Layfield R. J Proteomics Bioinform. (2013) S7:1-7.
  • Immunoproteasome activation during early antiviral response 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) 4(2).
  • 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.

Full list of publications in PubMed: Skowyra D
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
  • Enzyme replacement therapy in newborn mucopolysaccharidosis IVA mice: Early treatment rescues bone lesions?
    Tomatsu S, Montano AM, et al. Mol Genet Metab. (2014) Jun 4 [Epub ahead of print].
  • Expression patterns and subcellular localization of carbonic anhydrases are developmentally regulated during tooth formation.
    Reibring CG, El Shahawy M, et al. PLoS One. (2014) 9(5):e96007.
  • Luminol-based chemiluminescent signals: clinical and non-clinical application and future uses.
    Khan P, Idrees D, et al. Appl biochem Biotechnol. (2014) 173(2):333-355.
  • Expression of cancer-related carbonic anhydrases IX and XII in normal skin and skin neoplasms.
    Syrjanen L, Luukkaala T, et al. APMIS. (2014) 122(9):880-90.
  • Mitochondrial carbonic anhysrase VA deficiency resulting from CA5A alterations presents with hyperammonemia in early childhood.
    van Karnebeek CD, Sly WS, et al. Am J Hum Genet. (2014) 94(3):453-461.
  • High resolution crystal structure of human beta-glucuronidase reveals structural basis of lysosome targeting.
    Hassan MI, Waheed A, et al. PLoS One. (2013) 8(11):e79687.
  • Membrane associated carbonic anhydrase IV (CA IV): A personal and historical perspective.
    Waheed A, Sly WS. Subcell. Biochem. (2014) 75:157-79.
  • Enzyme replacement therapy on hypophosphatasia mouse model.
    Oikawa H, Tomatsu S, et al. J Inherit Metab Dis. (2013) 37(2):309-17.
  • Activity and distribution of intracellular carbonic anhydrase II and their effects on the transport activity of anion exchanger AE1/SLC4A1.
    Al-Samir S, Papadopoulos S, et al. J Physiol. (2013) 591(Pt 20):4963-4982.
  • Human beta-glucuronidase: Structure, function and application in enzyme replacement therapy.
    Naz H, Islam A, et al. Rejuvenation Res. (2013) 16(5):352-363.
  • The final frontier - Crossing the blood-brain barrier.
    Sly WS and Vogler C. EMBO Mol Med. (2013) 5(5):655-7.
  • 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.
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
  • Identification of RECQ1-regulated transcriptome uncovers a role of RECQ1 in regulation of cancer cell migration and invasion.
    Li XL, Lu X, et al. Cell Cycle. (2014) Jun 16, 13(15) [Epub ahead of print].
  • Discovery of ML216, a small molecule inhibitor of Bloom (BLM) helices.
    Rosenthal AS, Dexheimer TS, et al. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US). (updated 2013 Feb 28).
  • The two faces of DNA repair: disease and therapy.
    Vindigni A, Gonzalo S. Mo Med. (2013) 110(4):314-319.
  • 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) 20(3):347-54.

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
  • The double life of antibiotics.
    Yap MN. Mo Med. (2013) 110(4):320-324.
  • Mutations in the Escherichia coli ribosomal protein L22 selectively suppress the expression of a secreted bacterial virulence factor.
    Yap MN, Bernstein HD. J Bacteriol. (2013) 195(13):2991-9.