Edward A. Doisy Department of
Biochemistry and Molecular Biology

Primary Faculty

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.
  • Functional mapping of the interaction between TDP-43 and nRNP A2 in vivo.
    D-Ambrogio A, Buratti E, et al. Nucleic Acids Res. (2009) 37:4116-4126.
  • 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.

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
  • miR-27b inhibits LDLR and ABCA1 expression but does not influence plasma and hepatic lipid levels in mice.
    Goedecke L, Rotllan N, et al. Atherosclerosis. (2015) 243(2):499-509.
  • Akt-mediated FoxO1 inhibition is required for liver regeneration.
    Pauta M, Rotllan N, et al. Hepatology. (2015) [Epub ahead of print].
  • CIDEC/FSP27 is regulated by peroxisome proliferator-activated receptor alpha and plays a critical role in fasting- and diet-induced hepatosteatosis.
    Langhi C, Baldán A. Hepatology. (2015) 61(4):1227-1238.
  • ABCG1 is required for pulmonary B-1 B cell and natural antibody homeostasis.
    Baldán A, Gonen A, et al. J Immunol. (2014) 193(11):5637-5648.
  • 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.
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.
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
  • Optogenetic control of chemokine receptor signal and T-cell migration.
    Xu Y, Hyun YM, et al. Proc Natl Acad Sci USA. (2014) 111(17):6371-6376.
  • Quest for new biomarkers in atherosclerosis.
    Cho Y, Baldán A. Mo Med. (2013) 110(4):325-330.
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.
M.D., 1985, Catholic University School of Medicine, Rome, Italy.
Research Interests
We are interested in the structure, function and engineering of trypsin-like proteases and their zymogen forms. The main focus of the lab is on thrombin and prothrombin as key components of the blood coagulation system. Our experimental approach includes kinetics, thermodynamics, site-directed mutagenesis, X-ray structural biology and single molecule spectroscopy.
Recent Publications
  • Kinetic dissection of the pre-existing conformational equilibrium in the trypsin fold.
    Vogt AD, Chakraborty P, Di Cera E. J Biol Chem. (2015) 290(37):22435-22445.
  • John A. Schellman, 1924-2014.
    Di Cera E. Biophys Chem. (2015) Jan 15 [Epub ahead of print].
  • Why ser and not thr brokers catalysis in the trypsin fold.
    Pelc LA, Chen Z, et al. Biochemistry. (2015) 54(7):1457-64.
  • WEDGE: An anticoagulant thrombin mutant produced by autoactivation.
    Wood DC, Pelc LA, et al. J Thromb Haemost. (2014) 13(1):111-4.
  • Prothrombin structure: Unanticipated features and opportunities.
    Pozzi N, Di Cera E. Expert Rev Proteomics. (2014) 11(6):653-5.
  • 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.
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
  • Drosophila nipped-B mutants model Cornelia de Lange syndrome in growth and behavior.
    Wu Y, Gause M, et al. PLoS Genet. (2015) 11(11):e1005655.
  • Clinical, developmental and molecular update on Cornelia de Lange syndrome and the cohesion complex: Abstracts form he 2014 Scientific and Educational Symposium.
    Kline AD, Calof AL, et al. Am J Med Genet. (2015) 167(6):1179-1192.
  • Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin.
    Izumi K, Nakato R, et al. Nat Genet. (2015) 47(4):338-344.
  • HCoDES reveals chromosomal DNA end structures with single-nucleotide resolution.
    Dorsett Y, Zhou Y, et al. Mol Cell. (2014) 56(6):808-818.
  • 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.
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
  • Different pathways to the lysosome: Sorting out alternatives.
    Hasanagic M., Waheed A, Eissenberg JC. Int Rev Cell Mol Biol. (2015) 320:75-101.
  • The lysosomal enzyme receptor protein (LERP) is not essential, but is implicated in lysosomal function in Drosophila melanogaster.
    Hasanagic M., van Meel S., et al. Biol Open. (2015) 4:1316-1325.
  • The Nobel path of cellular proteins.
    Eissenberg JC, Sly WS. Mo Med. (2014) 111:114-119.
  • Epigenetics: modifying the genetic blueprint.
    Eissenberg JC. Mo Med. (2014) 111:428-433.
  • 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.
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
  • Akt-mediated FoxO1 inhibition is required for liver regeneration.
    Pauta M, Rotllan N, et al. Hepatology. (2015) [Epub ahead of print].
  • Identification of glutathione adducts of alpha-chlorofatty aldehydes produced in activated neutrophils.
    Duerr MA, Aurora R, Ford DA. J Lipid Res. (2015) 56(5):1014-1024.
  • Lpcat3-dependent production of arachidonoly phospholipids is a key determinant of triglyceride secretion.
    Rong X, Wang B, et al. Elife. (2015) 4:e06557.
  • Dipeptidyl peptidase-4 inhibition ameliorates western diet-induced hepatic steatosis and insulin resistance through hepatic lipid remodeling and modulation of hepatic mitochondrial function.
    Aroor AR, Habibi J, et al. Diabetes. (2015) 64(6):1988-2001.
  • PON3 knockout mice are susceptible to obesity, gallstone formation, and atherosclerosis.
    Shih DM, Yu JM, et al. FASEB J. (2015) 29(4):1185-1197.
  • ABCG1 is required for pulmonary B-1 B cell and natural antibody homeostasis.
    Baldan A, Gonen A, et al. J Immunol. (2014) 193(11):5637-5648.
  • 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) 289(43):1834-1842.
  • Alpha-chlorofatty acid and coronary artery or aorta calcium scores in women with systemic lupus erythematosus. A pilot study.
    Mahieu MA, Guild CP, et al. J Rheumatol. (2014) 41(9):1834-1842.
  • 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.
  • Oxidation of plasmalogen, low-density lipoprotein and RAW 264.7 cells by photoactivatable atomic oxygen precursors.
    Bourdillon MT, Ford BA, et al. Photochem Photobiol. (2014) 90(2):386-393.
  • 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.
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
  • Loss of lamin A function increases chromatin dynamics in the nuclear interior.
    Bronshtein I, Kepten E, et al. Nat Commun. (2015) 6:8044-8052.
  • DNA repair defects and genome instability in Hutchinson-Gilford Progeria Syndrome.
    Gonzalo S, Kreienkamp R. Curr Opin Cell Biol. (2015) 34:75-83.
  • 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.
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
  • Real-time observation of back tracking by bacterial RNA polymerase.
    Lass-Napiorkowska A and Heyduk T. Biochemistry. (2016) Jan 8 [Ebup ahead of print]. PubMed PMID: 26745324
  • Next generation sequencing-based analysis of RNA polymerase functions.
    Heyduk T and Heyduk E. Methods. (2015) 86:37-44. PubMed PMID: 25937393
  • 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
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.
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.
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
  • Correction: High resolution crystal structure of human beta-glucuronidase reveals structural basis of lysosome targeting.
    Hassan MI, Waheed A, et al. PLoS One. (2015) 10(9):e0138401.
  • RecO protein initiates DNA recombination and strand annealing through two alternative DNA binding mechanisms.
    Ryzhikov M, Gupta R, et al. J Biol Chem. (2014) 289(42):28846-28855.
  • 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.
Ph.D., 2010, University of Padua, Italy.
Research Interests
Our laboratory studies the structure, function and dynamics of proteins that are mistakenly targeted by autoantibodies in autoimmune disorders such as Antiphosholipid Syndrome (APS), Systemic Lupus Erythematous (SLE) and Rheumatoid Arthritis (RA). Our aim is to understand the origin of the autoantibodies, how the antigen-antibody recognition occurs at the molecular level and what are the molecular pathways involved in the transduction of the signal. Our goal is to develop strategies to diagnose, manage or treat the onset and progression of the disease. To achieve our goals, we apply a unique combination of cell and molecular biology, protein engineering, X-ray crystallography, single molecule fluorescence spectroscopy (smFRET and FCS) and surface plasmon resonance (SPR).
Recent Publications
  • Why ser and not thr brokers catalysis in the trypsin fold.
    Pelc LA, Chen Z, et al. Biochemistry. (2015) 54(7):1457-64.
  • WEDGE: An anticoagulant thrombin mutant produced by autoactivation.
    Wood DC, Pelc LA, et al. J Thromb Haemost. (2014) 13(1):111-4.
  • Prothrombin structure: Unanticipated features and opportunities.
    Pozzi N, Di Cera E. Expert Rev Proteomics. (2014) 11(6):653-5.
  • 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.
  • Essential role of conformational selection in ligand binding.
    Vogt AD, Pozzi N, et al. Biophys Chem. (2014) 186:13-21.
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
  • Coagulation factor V mediates inhibition of tissue factor signaling by activated protein C in mice.
    Liang HP, Kerschen EJ, et al. Blood. (2015) 126(21):2415-2423.
  • Expression and characterization of Gly-317 variants of Factor IX causing variable bleeding in Hemophilia B patients.
    Lu Q, Yang L, et al. Biochemistry. (2015) 54(24):3814-3821.
  • Inorganic polyphosphate elicits pro-inflammatory responses through activation of the mammalian target of rapamycin complexes 1 and 2 in vascular endothelial cells.
    Hassanian SM, Dinarvand P, et al. J Thromb Haemost. (2015) 13(5):860-871.
  • Protein C Thr315Ala variant results in gain-of-function but manifests as type II deficiency in diagnostic assays.
    Ding Q, Yang L, et al. Blood. (2015) 125(15):2428-2434.
  • Intraperitoneal administration of activated protein C prevents post surgical adhesion band formation.
    Dinarvand P, Hassanian SM, et al. Blood. (2015) 125(8):1339-1348.
  • Conformational activation of antithrombin by heparin involves an altered exosite interaction with protease.
    Izaguirre G, Aguila S, et al. J Biol Chem. (2014) 289(49):34049-34064.
  • Antithrombin up-regulates AMP-activated protein kinase signalling during myocardial ischaemia/reperfusion injury.
    Ma Y, Wang J, et al. Thromb Haemost. (2014) 113(2):338-349.
  • 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) 134(5):1103-1109.
  • Protease-activated receptor signalling by coagulation proteases in endothelial cells.
    Rezaie AR. Thromb Haemost. (2014) 112(5):876-882.
  • Characterization of the protein Z-dependent protease inhibitor interactive-sites of protein Z.
    Qureshi SH, Lu Q, et al. Biochim Biophys Acta. (2014) 1844(9):1631-1637.
  • 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.
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
  • Urinary organic acids quantitated in a healthy north Indian pediatric population.
    Kumari C, Singh A, et al. Indian J Clin Biochem. (2015) 30(2):221-9.
  • 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.
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
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
  • Pharmacologic manipulation of lysosomal enzyme transport across the blood-brain barrier.
    Urayama A, Grubb JH, et al. J Cereb Blood Flow Metab. (2015) Nov 3 [Epub ahead of print].
  • Alpha adrenergic induction of transport of lysosomal enzyme across the blood-brain barrier.
    Urayama A, Dohgu S, et al. PLoS One. (2015) 10(11):e0142347.
  • Normal fertility requires expression of carbonic anhydrases II and IV in sperm.
    Wandernoth PM, Mannowetz N, et al. J Biol Chem. (2015) 290(49):29202-29216.
  • Large scale analysis of the mutational landscape in beta-glucuronidase: A major player of mucopolysaccahridosis type VII.
    Khan FI, Shahbaaz M, et al. Gene. (2015) 576(Pt 1):36-44.
  • Correction: High resolution crystal structure of human beta-glucuronidase reveals structural basis of lysosome targeting.
    Hassan MI, Waheed A, et al. PLoS One. (2015) 10(9):e0138401.
  • Therapies for the bone in mucopolysaccharidosis.
    Tomatsu S, Almeciga-Diaz CJ, et al. Mol Genet Metab. (2015) 114(2):94-109.
  • First human treatment with investigational rhGUS enzyme replacement therapy in an advanced stage MPS VII patient.
    Fox JE, Volpe L, et al. Mol Genet Metab. (2015) 114(2):203-208.
  • The Nobel path of cellular proteins.
    Eisenberg JC, Sly WS. Mo Med. (2014) 111:114-119.
  • Morquio A syndrome: diagnosis and current and future therapies.
    Tomatsu S, Yasuda E, et al. Pediatr Endocrinol. (2014) 12(Suppl 1):141-151.
  • Enzyme replacement therapy in newborn mucopolysaccharidosis IVA mice: Early treatment rescues bone lesions?
    Tomatsu S, Montano AM, et al. Mol Genet Metab. (2015) 114(2):195-202.
  • 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.
Ph.D., 1995, University of Padua, Italy
Research Interests
My group uses a combination of cellular, biochemical, and structural approaches to study the enzymatic activity and function of the human RecQ helicases, a family of enzymes that play a key role in the maintenance of genome integrity. RecQ helicases have attracted considerable interest in recent years, not only because of their role in the maintenance of chromosome stability, but also for their connection to disorders associated with cancer predisposition and premature aging.
Recent Publications
  • Fourier transform infrared microspectroscopy reveals biochemical changes associated with glioma stem cell differentiation.
    Kenig S, Bedolla DE, et al. Biophys Chem. (2015) 207:90-96.
  • Human RECQ1 helicase-driven DNA unwinding, annealing, and branch migration: Insights from DNA complex structures.
    Pike ACW, Gomathinayagam S, et al. Proc Natl Acad Sci USA. (2015) 112(14):4286-4291.
  • Rad51-mediated replication fork reversal is a global response to genotoxic treatments in human cells.
    Zellweger R, Dalcher D, et al. J Cell Biol. (2015) 208(5):563-579.
  • DNA2 drives processing and restart of reversed replication forks in human cells.
    Thangavel S, Berti M, et al. J Cell Biol. (2015) 208(5):545-562.
  • 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) 13(15):2431-2445.

Full list of publications in PubMed: Vindigni A
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
  • Sequence selectivity of macrolide-induced translational attenuation.
    Davis AR, Gohara DW, Yap MN. Proc Natl Acad Sci USA. (2014) 111(43):15379-15384.
  • 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.