Positions

Overview

  • Mary-Ann Bjornsti, Ph.D., is Chair of the Department of Pharmacology and Toxicology at UAB, and holds the Newman H. Waters Chair of Clinical Pharmacology. She also serves as co-Leader of the Cancer Cell Biology Program and Associate Director for Translational Research in the UAB Comprehensive Cancer Center. She received her Ph.D. from the University of Minnesota in Genetics, followed by a Fogarty Fellowship at the Biozentrum in Basel Switzerland, and post-doctoral training at Harvard University with Dr. James C. Wang.

    In 1989, she set up her own lab as an Assistant, then Associate Professor at Thomas Jefferson University in Philadelphia. In 1999, she joined the faculty at St. Jude Children’s Research Hospital and was promoted to Full Member. In 2009, she was recruited to UAB as Department Chair. Her long-standing, research interests are in the mechanisms of anti-cancer drug action and in pathways regulating tumor growth and cellular responses to replicative stress. Her lab pioneered the use of the genetically tractable yeast model system to investigate the mechanism of action of DNA topoisomerase I and experimental chemotherapeutics that target this enzyme, with a focus on translating basic mechanisms of chemotherapeutic drug action and cellular pathways that regulate drug responses to human cell lines and mouse models. Her lab actively collaborates with members of the UAB Comprehensive Cancer Center and other UAB researchers to investigate SUMO and mTOR signaling pathways that regulate cancer cell responses to genotoxic stresses.

    She is also on the Executive committee for the Alabama Drug Discovery Alliance (ADDA) and has been actively pursuing the development of novel SUMO pathway inhibitors. She serves on several advisory and editorial boards, is on the Science Policy committees for ASPET and FASEB, is past-President of the Association for Medical School Pharmacology Chairs, Chair-elect for the Cancer Pharmacology Division at ASPET, has organized numerous national and international meetings, and chairs an NIH SBIR/STTR study section. She co-chairs a UAB Translational Concepts meeting with Dr. Mansoor Saleh and serves on the Executive Committee for the UAB National Clinical Trial Network (NCTN) Lead Academic Participating Site (LAPS) program.
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2019 UBC9 Mutant Reveals the Impact of Protein Dynamics on Substrate Selectivity and SUMO Chain LinkagesBiochemistry2019
    2017 DNA topoisomerase-targeting chemotherapeutics: what’s new?Cancer Chemotherapy and Pharmacology.  80. 2017
    2016 Molecular Mechanism of DNA Topoisomerase I-Dependent rDNA Silencing: Sir2p Recruitment at Ribosomal GenesJournal of Molecular Biology.  428:4905-4916. 2016
    2016 Acoustic Droplet Ejection Technology and Its Application in High-Throughput RNA Interference ScreeningJournal of Laboratory Automation.  21:198-203. 2016
    2015 DNA topoisomerase I domain interactions impact enzyme activity and sensitivity to camptothecinJournal of Biological Chemistry.  290:12068-12078. 2015
    2015 Tyrosyl-DNA phosphodiesterase I catalytic mutants reveal an alternative nucleophile that can catalyze substrate cleavageJournal of Biological Chemistry.  290:6203-6214. 2015
    2015 Point mutations of the mTOR-RHEB pathway in renal cell carcinomaOncotarget.  6:17895-17910. 2015
    2013 Development and Histopathological Characterization of Tumorgraft Models of Pancreatic Ductal AdenocarcinomaPLoS ONE.  8. 2013
    2013 4-hydroxytamoxifen induces autophagic death through K-Ras degradationCancer Research.  73:4395-4405. 2013
    2013 High-Throughput RNA Interference Screening: Tricks of the TradeJournal of Laboratory Automation.  18:334-339. 2013
    2010 Cellular strategies for regulating DNA supercoiling: A single-molecule perspectiveCell.  142:519-530. 2010
    2008 Disulfide cross-links reveal conserved features of DNA topoisomerase I architecture and a role for the N terminus in clamp closureJournal of Biological Chemistry.  283:27767-27775. 2008
    2008 Mutation of Gly721 alters DNA topoisomerase I active site architecture and sensitivity to camptothecinJournal of Biological Chemistry.  283:3305-3315. 2008
    2007 TOR signaling is a determinant of cell survival in response to DNA damageMolecular and Cellular Biology.  27:7007-7017. 2007
    2007 Mutation of a Conserved Active Site Residue Converts Tyrosyl-DNA Phosphodiesterase I into a DNA Topoisomerase I-dependent PoisonJournal of Molecular Biology.  372:1070-1081. 2007
    2007 Antitumour drugs impede DNA uncoiling by topoisomerase INature.  448:213-217. 2007
    2007 Structure of a SUMO-binding-motif Mimic Bound to Smt3p-Ubc9p: Conservation of a Non-covalent Ubiquitin-like Protein-E2 Complex as a Platform for Selective Interactions within a SUMO PathwayJournal of Molecular Biology.  369:619-630. 2007
    2007 Inhibition of topoisomerase I cleavage activity by thiol-reactive compounds: Importance of vicinal cysteines 504 and 505Journal of Biological Chemistry.  282:14403-14412. 2007
    2007 Alterations in linker flexibility suppress DNA topoisomerase I mutant-induced cell lethalityJournal of Biological Chemistry.  282:9855-9864. 2007
    2006 Trapping of DNA topoisomerase I on nick-containing DNA in cell free extracts of Saccharomyces cerevisiaeDNA Repair.  5:799-809. 2006
    2006 Distinct functional domains of Ubc9 dictate cell survival and resistance to genotoxic stressMolecular and Cellular Biology.  26:4958-4969. 2006
    2005 Defects in SUMO (small ubiquitin-related modifier) conjugation and deconjugation alter cell sensitivity to DNA topoisomerase I-induced DNA damageJournal of Biological Chemistry.  280:23566-23575. 2005
    2005 Enhanced antitumor activity of irofulven in combination with irinotecan in pediatric solid tumor xenograft modelsCancer Chemotherapy and Pharmacology.  55:411-419. 2005
    2004 Platinated DNA adducts enhance poisoning of DNA topoisomerase I by camptothecinJournal of Biological Chemistry.  279:54502-54509. 2004
    2004 Substitution of conserved residues within the active site alters the cleavage religation equilibrium of DNA topoisomerase IJournal of Biological Chemistry.  279:54069-54078. 2004
    2004 The deubiquitinating enzyme Doa4p protects cells from DNA topoisomerase I poisonsJournal of Biological Chemistry.  279:21271-21281. 2004
    2004 Homologous recombination is a highly conserved determinant of the synergistic cytotoxicity between cisplatin and DNA topoisomerase I poisonsMolecular Cancer Therapeutics.  3:393-402. 2004
    2004 Lost in translation: Dysregulation of cap-dependent translation and cancerCancer Cell.  5:519-523. 2004
    2004 The TOR pathway: A target for cancer therapyNature Reviews Cancer.  4:335-348. 2004
    2003 Locking the DNA topoisomerase I protein clamp inhibits DNA rotation and induces cell lethalityProceedings of the National Academy of Sciences.  100:13767-13772. 2003
    2003 Rapamycins: Mechanism of action and cellular resistanceCancer Biology and Therapy.  2:222-232. 2003
    2003 A novel active DNA topoisomerase I in Leishmania donovaniJournal of Biological Chemistry.  278:3521-3526. 2003
    2002 Active site mutations in DNA topoisomerase I distinguish the cytotoxic activities of camptothecin and the indolocarbazole, rebeccamycinJournal of Biological Chemistry.  277:3813-3822. 2002
    2002 Cancer therapeutics in yeastCancer Cell.  2:267-273. 2002
    2001 Drug-induced stabilization of covalent DNA topoisomerase I-DNA intermediates. DNA cleavage assays.Methods in Molecular Biology.  95:291-301. 2001
    2001 Studying DNA topoisomerase I-targeted drugs in the yeast. Saccharomyces cerevisiae.Methods in Molecular Biology.  95:303-313. 2001
    2000 Substitutions of Asn-726 in the active site of yeast DNA topoisomerase I define novel mechanisms of stabilizing the covalent enzyme-DNA intermediateJournal of Biological Chemistry.  275:15246-15253. 2000
    1999 CDC45 and DPB11 are required for processive DNA replication and resistance to DNA topoisomerase I-mediated DNA damageProceedings of the National Academy of Sciences.  96:11440-11445. 1999
    1999 Induction of reversible complexes between eukaryotic DNA topoisomerase I and DNA-containing oxidative base damages: 7,8-dihydro-8-oxoguanine and 5- hydroxycytosineJournal of Biological Chemistry.  274:8516-8523. 1999
    1999 Cascades of mammalian caspase activation in the yeast Saccharomyces cerevisiaeJournal of Biological Chemistry.  274:3189-3198. 1999
    1999 Domain interactions affecting human DNA topoisomerase I catalysis and camptothecin sensitivityMolecular Pharmacology.  56:1105-1115. 1999
    1999 Introduction to DNA topoisomerases.Methods in Molecular Biology.  94:1-8. 1999
    1999 Overexpression and purification of DNA topoisomerase I from yeast.Methods in Molecular Biology.  94:179-186. 1999
    1999 Resolution of DNA molecules by one-dimensional agarose-gel electrophoresis.Methods in Molecular Biology.  94:9-17. 1999
    1998 Analysis of comptothecin resistance in yeast: relevance to cancer therapyDrug Resistance Updates.  1:176-183. 1998
    1998 Intragenic suppressors of mutant DNA topoisomerase I-induced lethality diminish enzyme binding of DNAJournal of Biological Chemistry.  273:31519-31527. 1998
    1998 Induction of topoisomerase I cleavage complexes by the vinyl chloride adduct 1,N6-ethenoadenineJournal of Biological Chemistry.  273:27245-27249. 1998
    1998 Yeast as a model organism for studying the actions of DNA topoisomerase- targeted drugsBBA - Gene Structure and Expression.  1400:289-300. 1998
    1998 Increased camptothecin toxicity induced in mammalian cells expressing Saccharomyces cerevisiae DNA topoisomerase IJournal of Biological Chemistry.  273:8425-8433. 1998
    1997 Alterations in the catalytic activity of yeast DNA topoisomerase I result in cell cycle arrest and cell deathJournal of Biological Chemistry.  272:12801-12808. 1997
    1997 Camptothecin sensitivity is mediated by the pleiotropic drug resistance network in yeastJournal of Biological Chemistry.  272:12091-12099. 1997
    1996 Topoisomerase II-etoposide interactions direct the formation of drug- induced enzyme-DNA cleavage complexesJournal of Biological Chemistry.  271:29238-29244. 1996
    1995 Chromosome Band 11q23 Translocation Breakpoints Are DNA Topoisomerase II Cleavage SitesCancer Research.  55:4287-4292. 1995
    1995 SCT1 mutants suppress the camptothecin sensitivity of yeast cells expressing wild-type DNA topoisomerase IProceedings of the National Academy of Sciences.  92:6299-6303. 1995
    1995 Expression of a Deletion Mutant of the E2F1 Transcription Factor in Fibroblasts Lengthens S Phase and Increases Sensitivity to S Phase-specific ToxinsCancer Research.  55:2883-2891. 1995
    1995 A camptothecin-resistant DNA topoisomerase I mutant exhibits altered sensitivities to other DNA topoisomerase poisonsJournal of Biological Chemistry.  270:6141-6148. 1995
    1994 Yeast Saccharomyces cerevisiae as a model system to study the cytotoxic activity of the antitumor drug camptothecinCancer Chemotherapy and Pharmacology.  34. 1994
    1993 A novel mutation in DNA topoisomerase I of yeast causes DNA damage and RAD9-dependent cell cycle arrestGenetics.  133:799-814. 1993
    1993 Inhibition of Human Neurotropic Virus (JCV) DNA Replication in Glial Cells by CamptothecinVirology.  196:612-618. 1993
    1993 Mechanisms of camptothecin resistance in yeast DNA topoisomerase I mutantsJournal of Biological Chemistry.  268:22322-22330. 1993
    1991 DNA topoisomerases. Current Opinion in Structural Biology 1991, 1:99-103Current Opinion in Structural Biology.  1:99-103. 1991
    1989 Expression of Human DNA Topoisomerase I in Yeast Cells Lacking Yeast DNA Topoisomerase I: Restoration of Sensitivity of the Cells to the Antitumor Drug CamptothecinCancer Research.  49:6318-6323. 1989
    1989 Peptide sequencing and site-directed mutagenesis identify tyrosine-727 as the active site tyrosine of Saccharomyces cerevisiae DNA topoisomerase I.Proceedings of the National Academy of Sciences.  86:3559-3563. 1989
    1988 Intracellular location of the histonelike protein HU in Escherichia coli.Journal of Bacteriology.  170:4757-4768. 1988
    1987 Expression of yeast DNA topoisomerase I can complement a conditional-lethal DNA topoisomerase I mutation in Escherichia coli.Proceedings of the National Academy of Sciences.  84:8971-8975. 1987
    1987 Use of on-section immunolabeling and cryosubstitution for studies of bacterial DNA distributionJournal of Bacteriology.  169:2055-2062. 1987
    1985 Morphogenesis of bacteriophage phi29 of Bacillus subtilis: Prohead restoration for DNA-gp3 packaging and assemblyJournal of Virology.  53:858-861. 1985
    1984 Bacteriophage φ29 proteins required for in vitro DNA-gp3 packagingJournal of Virology.  50:766-772. 1984
    1983 Morphogenesis of bacteriophage φ29 of Bacillus subtilis: Oriented and quantized in vitro packaging of DNA protein gp3Journal of Virology.  45:383-396. 1983
    1982 Morphogenesis of bacteriophage Φ29 of Bacillus subtilis: DNA-gp3 intermediate in in vivo and in vitro assemblyJournal of Virology.  41:508-517. 1982
    1981 In vitro assembly of the Bacillus subtilis bacteriophage φ29Proceedings of the National Academy of Sciences.  78:5861-5865. 1981

    Chapter

    Year Title Altmetric
    2015 The ubiquitin/proteasome pathway in neoplasia.  473-480. 2015
    2012 Mechanisms regulating cellular responses to DNA topoisomerase I-targeted agents.  325-334. 2012

    Research Overview

  • Mary-Ann Bjornsti, PhD has long-standing research interests in the mechanisms of anti-cancer drug action and in pathways regulating tumor growth and chemotherapeutic response. As a post-doc at Harvard University, she pioneered the use of the genetically tractable yeast model system to investigate the mechanism of action of DNA topoisomerase I and chemotherapeutics that target this enzyme. At Thomas Jefferson University, her lab expanded these studies to include genetic and biochemical studies of cellular pathways dictating tumor cell response to these drugs. At St Jude Children’s Research Hospital and at UAB, her lab has focused on translating basic mechanisms of chemotherapeutic drug action and cellular pathways that regulated responses to these agents to human cell lines and mouse models. Her lab has partnered with the UAB Alabama drug discovery alliance and Southern Research to establish genome-wide siRNA screening capabilities that complement state-of-the-art chemistry and small molecule screening platforms at Southern Research. She had developed extensive collaborative efforts with Members of the UAB Comprehensive Cancer Center and the Breast Cancer SPORE to investigate pathways that regulate cellular responses to topoisomerase I-induced DNA damage, the functional consequences of protein SUMOylation on cellular responses to genotoxic stresses, and the role of TOR signaling in the DNA damage response.
  • Teaching Activities

    Education And Training

  • Doctor of Philosophy in Genetics, University of Minnesota System : Twin Cities 1983
  • Full Name

  • Mary-Ann Bjornsti