Steven D Goodman, PhD :: Nationwide Children's Hospital, Columbus, Ohio

Steven D Goodman, PhD

Steven D Goodman, PhD

Center for Microbial Pathogenesis
Principal Investigator

Contact Information

700 Children's Drive
Columbus, OH 43205 [ map ]
E-mail Me

Biography

Dr. Goodman is a principal investigator in the Center for Microbial Pathogenesis. His research focuses on gene regulation in biofilms, bacterial surface detection and attachment, horizontal gene transfer (HGT) and metagenomics, and bacterial histones. 1. Gene Regulation in Biofilms: In nature, bacteria are often found in complex microbial ecosystems. In some cases these bacteria associate to form interactive systems commonly referred to as biofilms. The oral cavity is home to hundreds of bacteria. One of these bacteria, Streptococcus mutans, causes dental caries (cavities) and is known to form biofilms (plaque) on the surface of teeth. Critical to the formation of these biofilms are the genes required to adhere to teeth. We have found that the expression of these genes is strongly regulated and coupled to the ability of the bacteria to sense their environment (e.g. when they encounter the surface of a tooth.) One of the ways that bacteria can do this is through Two Component Signal Transduction Systems (TCSTS). These systems are composed of a membrane bound protein that upon sensing a specific environmental signal alters the function of a specific transcription factor. Each TCSTS has a repertoire of genes whose expression is specifically affected upon signal detection. S. mutans has 13 TCSTS and it is our long term goal to clone, express and determine the biological function(s) of each one. In this way, we will be able to determine what S. mutans senses and how it responds. 2. Bacterial Surface Detection and Attachment: In an extension of our work above and in collaboration with Ken Nealson (Earth Sciences, LAS, USC) and Firdaus Udwadia (Aeropsace and Mechanical Engineering, ENG. USC), it has become very clear that bacteria are exquisite sensors of surfaces as they do not attach randomly to a given surface. We are identifying the surface/material properties that the bacteria need to choose where to attach and finding out what genes are involved in the process. 3. Horizontal Gene Transfer (HGT) and Metagenomics: Bacteria can spread and exchange their genetic information in three ways, namely conjugation (bacterial sex), transduction (viral mediated) and transformation (uptake of extracellular DNA). Recently it has become clear that in a given ecological niche HGT occurs so rampantly that bacteria are believed to have access to the largess of genetic information for all of the constituent bacteria (aka the metagenome). We have discovered a bacteriophage that propagates in the oral cavity by both infection with its native host, a periodontal pathogen Aggregatibacter actinomycetemcomintans, and by transformation. We are using this bacteriophage as a model system to determine which routes of HGT are most likely to explain how genes (e.g. those that encode antibiotic resistance) are spread from one bacterium to another. 4. Bacterial Histones: IHF is a small abundant bacterial protein that binds to and bends a specific DNA sequence. IHF always seems to act in an accessory capacity and is known to function in virtually all types of nucleoprotein systems (e.g. replication, gene expression, and recombination). Thus it has been proposed that IHF modulates (activates or represses) the systems where it acts through DNA bending. In this way, it functionally resembles eukaryotic histones. Recently, we have discovered that IHF and a related protein HU play a critical role in the extracellular matrix of pathogenic biofilms. This matrix protects bacteria from the immune system and antimicrobial therapies and causes chronicity of bacterial infections. In collaboration with Lauren Bakaletz (Center for Microbial Pathogenesis) we have developed an immunotherapeutic approach to remove these proteins from the biofilm causing the subsequent release of bacteria from their protective shield and making them vulnerable to clearance by both antibiotics and the immune system

Gender:

  • Male

Languages Spoken:

  • English

Research Interests

Research Center:

Areas of Interest:

  • Chronic and recurrent infectious disease
  • Biofilms
  • Nucleoprotein complexes

Education and Training

Undergraduate School

  • University of Pennsylvania, Pennsylvania
    Date Completed: 06/01/1981

Doctorate

  • Johns Hopkins University, Baltimore, Maryland
    Date Completed: 06/01/1988

Fellowship

  • National Institutes of Health, Maryland
    Date Completed: 09/01/1989

Professional Experience

2012–present

  • Principal Investigator, Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital

2009–2010

  • Associate Professor of Biomedical Sciences, University of Southern California

2009–2010

  • Chair, Biomedical Sciences, University of Southern California

2000–2012

  • Associate Professor, Biological Sciences, University of Southern California

1993–2000

  • Assistant Professor, Basic Sciences, University of Southern California

Publications

  • Lee,Chia-Chia; Yang,Ya-Chien; Goodman,Steven,D; Lin,Chien-Ju; Chen,Yi-an; Wang,Yi-Ting; Cheng,Wern-Cherng; Lin,Liang-In; Fang,Woei-Horng. 2013. The excision of 3 ' penultimate errors by DNA polymerase I and its role in endonuclease V-mediated DNA repair.  DNA REPAIR. Vol. 12, no. 11. (November): 899-911.
  • Brandstetter, KA, Jurcisek, JA, Goodman, SD, Bakaletz, LO, Das S. 2013. Antibodies directed against Integration Host Factor Mediate Biofilm Clearance from Nasopore®.  Laryngoscope. Vol. 123, no. November: e2626.
  • Gustave, JE, Jurcisek, JA, McCoy, KS, Goodman, SD and Bakaletz, LO. 2013. Targeting Bacterial Integration Host Factor to Disrupt Biofilms Associated with Cystic Fibrosis.  Journal of Cystic Fibrosis. Vol. 12, no. July: e384.
  • Novotny,Laura,A; Amer,Amal,O; Brockson,M,Elizabeth; Goodman,Steven,D; Bakaletz,Lauren,O. 2013. Structural Stability of Burkholderia cenocepacia Biofilms Is Reliant on eDNA Structure and Presence of a Bacterial Nucleic Acid Binding Protein.  PLOS ONE. Vol. 8, no. 6. (June): ee67629.
  • Wang,Chen; Sang,Jiayan; Wang,Jiawei; Su,Mingyan; Downey,Jennifer,S; Wu,Qinggan; Wang,Shida; Cai,Yongfei; Xu,Xiaozheng; Wu,Jun; Senadheera,Dilani,B; Cvitkovitch,Dennis,G; Chen,Lin; Goodman,Steven,D; Han,Aidong. 2013. Mechanistic Insights Revealed by the Crystal Structure of a Histidine Kinase with Signal Transducer and Sensor Domains.  PLOS BIOLOGY. Vol. 11, no. 2. (February): ee1001493.
  • Priyadarshini,Richa; Cugini,Carla; Arndt,Annette; Chen,Tsute; Tjokro,Natalia,O; Goodman,Steven,D; Davey,Mary,E. 2013. The nucleoid-associated protein HUß affects global gene expression in Porphyromonas gingivalis.  Microbiology (Reading, England). Vol. 159, no. February: 219-229.
  • Justice,Sheryl,S; Li,Birong; Downey,Jennifer,S; Dabdoub,Shareef,M; Brockson,M,Elizabeth; Probst,G,Duane; Ray,William,C; Goodman,Steven,D. 2012. Aberrant Community Architecture and Attenuated Persistence of Uropathogenic Escherichia coli in the Absence of Individual IHF Subunits.  PLOS ONE. Vol. 7, no. 10. (October): ee48349.
  • Senadheera,D,B; Cordova,M; AYALA,E,A; de Paz,L,EChavez; Singh,K; Downey,J,S; Svensater,G; Goodman,S,D; Cvitkovitch,D,G. 2012. Regulation of Bacteriocin Production and Cell Death by the VicRK Signaling System in Streptococcus mutans.  JOURNAL OF BACTERIOLOGY. Vol. 194, no. 6. (March): 1307-1316.
  • Hung,David,CI; Downey,Jennifer,S; Kreth,Jens; Qi,Fengxia; Shi,Wenyuan; Cvitkovitch,Dennis,G; Goodman,Steven,D. 2012. Oligomerization of the Response Regulator ComE from Streptococcus mutans Is Affected by Phosphorylation.  JOURNAL OF BACTERIOLOGY. Vol. 194, no. 5. (March): 1127-1135.
  • Goodman,S,D; Obergfell,K,P; Jurcisek,J,A; Novotny,L,A; Downey,J,S; AYALA,E,A; Tjokro,N; Li,B; Justice,S,S; Bakaletz,L,O. 2011. Biofilms can be dispersed by focusing the immune system on a common family of bacterial nucleoid-associated proteins.  MUCOSAL IMMUNOLOGY. Vol. 4, no. 6. (November): 625-637.
  • Hung,David,CI; Downey,Jennifer,S; Ayala,Eduardo,A; Kreth,Jens; Mair,Richard; Senadheera,Dilani,B; Qi,Fengxia; Cvitkovitch,Dennis,G; Shi,Wenyuan; Goodman,Steven,D. 2011. Characterization of DNA Binding Sites of the ComE Response Regulator from Streptococcus mutans.  JOURNAL OF BACTERIOLOGY. Vol. 193, no. 14. (July): 3642-3652.
  • Lino,M; Kus,J,V; Tran,S,L; Naqvi,Z; Binnington,B; Goodman,S,D; Segall,A,M; Foster,D,Barnett. 2011. A novel antimicrobial peptide significantly enhances acid-induced killing of Shiga toxin-producing Escherichia coli O157 and non-O157 serotypes.  MICROBIOLOGY-SGM. Vol. 157, no. June: 1768-1775.
  • Freire,Marcelo,O; Sedghizadeh,Parish,P; Schaudinn,Christoph; Gorur,Amita; Downey,Jennifer,S; Choi,Jeong-Ho; Chen,Weizhen; Kook,Joong-ki; Chen,Casey; Goodman,Steven,D; Zadeh,Homayoun,H. 2011. Development of an Animal Model for Aggregatibacter Actinomycetemcomitans Biofilm-Mediated Oral Osteolytic Infection: A Preliminary Study.  JOURNAL OF PERIODONTOLOGY. Vol. 82, no. 5. (May): 778-789.
  • Lee,Chia-Chia; Yang,Ya-Chien; Goodman,Steven,D; Yu,Yung-Hsu; Lin,Shwu-Bin; Kao,Jau-Tsuen; Tsai,Keh-Sung; Fang,Woei-Horng. 2010. Endonuclease V-mediated deoxyinosine excision repair in vitro.  DNA REPAIR. Vol. 9, no. 10. (October): 1073-1079.
  • Wu,Chenggang; Ayala,Eduardo,A; Downey,Jennifer,S; Merritt,Justin; Goodman,Steven,D; Qi,Fengxia. 2010. Regulation of ciaXRH Operon Expression and Identification of the CiaR Regulon in Streptococcus mutans.  JOURNAL OF BACTERIOLOGY. Vol. 192, no. 18. (September): 4669-4679.
  • Krastel,Kirsten; Senadheera,Dilani,B; Mair,Richard; Downey,Jennifer,S; Goodman,Steven,D; Cvitkovitch,Dennis,G. 2010. Characterization of a Glutamate Transporter Operon, glnQHMP, in Streptococcus mutans and Its Role in Acid Tolerance.  JOURNAL OF BACTERIOLOGY. Vol. 192, no. 4. (February): 984-993.
  • Summer,Heike; Li,Ou; Bao,Qiuye; Zhan,Lihong; Peter,Sabrina; Sathiyanathan,Padmapriya; Henderson,Dana; Klonisch,Thomas; Goodman,Steven,D; Droege,Peter. 2009. HMGA2 exhibits dRP/AP site cleavage activity and protects cancer cells from DNA-damage-induced cytotoxicity during chemotherapy.  NUCLEIC ACIDS RESEARCH. Vol. 37, no. 13. (July): 4371-4384.
  • Morash,Michael,G; Brassinga,Ann,Karen C; Warthan,Michelle; Gourabathini,Poornima; Garduno,Rafael,A; Goodman,Steven, D; Hoffman,Paul,S. 2009. Reciprocal Expression of Integration Host Factor and HU in the Developmental Cycle and Infectivity of Legionella pneumophila.  APPLIED AND ENVIRONMENTAL MICROBIOLOGY. Vol. 75, no. 7. (April): 1826-1837.
  • Waters,M,S; El-Naggar,M,Y; Hsu,L; Sturm,C,A; Luttge,A; Udwadia,F,E; Cvitkovitch,D,G; Goodman,S,D; Nealson,K,H. 2009. Simultaneous Interferometric Measurement of Corrosive or Demineralizing Bacteria and Their Mineral Interfaces.  APPLIED AND ENVIRONMENTAL MICROBIOLOGY. Vol. 75, no. 5. (March): 1445-1449.
  • Waters,M,S; SALAS,E,C; Goodman,S,D; Udwadia,F,E; Nealson,K,H. 2009. Early detection of oxidized surfaces using Shewanella oneidensis MR-1 as a tool.  BIOFOULING. Vol. 25, no. 2. (January): 163-172.
  • Waters,M,S; Sturm,C,A; El-Naggar,M,Y; Luttge,A; Udwadia,F,E; Cvitkovitch,D,G; Goodman,S,D; Nealson,K,H. 2008. In search of the microbe/mineral interface: quantitative analysis of bacteria on metal surfaces using vertical scanning interferometry.  GEOBIOLOGY. Vol. 6, no. 3. (June): 254-262.
  • Dunning,Daniel,W; McCall,Lathan,W; Powell,William,F; Arscott,W,Tristram; McConocha,Erin,M; McClurg,Cheryl,J; Goodman,Steven,D; Spatafora,Grace,A. 2008. SloR modulation of the Streptococcus mutans acid tolerance response involves the GcrR response regulator as an essential intermediary.  MICROBIOLOGY-SGM. Vol. 154, no. April: 1132-1143.
  • Kow,Yoke,W; Imhoff,Barry; Weiss,Bernard; Hung,David,CI; Hindoyan,Antreas,A; Story,Randall,M; Goodman,Steven,D. 2007. Escherichia coli HU protein has a role in the repair of abasic sites in DNA (Retracted Article. See vol 37, pg 3474, 2009).  NUCLEIC ACIDS RESEARCH. Vol. 35, no. 19. (October): 6672-6680.
  • Kreth,Jens; Hung,David,CI; Merritt,Justin; Perry,Julie; Zhu,Lin; Goodman,Steven,D; Cvitkovitch,Dennis,G; Shi,Wenyuan; Qi,Fengxia. 2007. The response regulator ComE in Streptococcus mutans functions both as a transcription activator of mutacin production and repressor of CSP biosynthesis.  MICROBIOLOGY-SGM. Vol. 153, no. June: 1799-1807.
  • Senadheera,M,Dilani; Lee,Andrew,WC; Hung,David,CI; Spatafora,Grace,A; Goodman,Steven,D; Cvitkovitch,Dennis,G. 2007. The Streptococcus mutans vicX gene product modulates gtfB/C expression, biofilm formation, genetic competence, and oxidative stress tolerance.  JOURNAL OF BACTERIOLOGY. Vol. 189, no. 4. (February): 1451-1458.
  • Qi,F,X; Kreth,J; Levesque,C,M; Kay,O; Mair,R,W; Shi,W,Y; Cvitkovitch,D,G; Goodman,S,D. 2005. Peptide pheromone induced cell death of Streptococcus mutans.  FEMS MICROBIOLOGY LETTERS. Vol. 251, no. 2. (October): 321-326.
  • Chuang,Y,K; Cheng,W,C; Goodman,S,D; Chang,Y,T; Kao,J,T; Lee,C,N; Tsai,K,S; Fang,W. 2005. Nick-directed repair of palindromic loop mismatches in human cell extracts.  JOURNAL OF BIOMEDICAL SCIENCE. Vol. 12, no. 4. (July): 659-669.
  • Senadheera,M,D; Guggenheim,B; Spatafora,G,A; An,Y,CCLG; Choi,J; Hung,D,CI; Treglown,J,S; Goodman,S,D; Ellen,R,P; Cvitkovitch,D,G. 2005. A VicRK signal transduction system in Streptococcus mutans affects gtfBCD, gbpB, and ftf expression, biofilm formation, and genetic competence development.  JOURNAL OF BACTERIOLOGY. Vol. 187, no. 12. (June): 4064-4076.
  • Huang,Y,M; CHEN,S,U; Goodman,S,D; Wu,S,H; Kao,J,T; Lee,C,N; Cheng,W,C; Tsai,K,S; Fang,W,H. 2004. Interaction of nick-directed DNA mismatch repair and loop repair in human cells.  JOURNAL OF BIOLOGICAL CHEMISTRY. Vol. 279, no. 29. (July): 30228-30235.
  • Shen,W,Q; Bruist,M,F; Goodman,S,D; Seeman,N,C. 2004. A protein-driven DNA device that measures the excess binding energy of proteins that distort DNA.  ANGEWANDTE CHEMIE-INTERNATIONAL EDITION. Vol. 43, no. 36. (January): 4750-4752.
  • Merritt,J; Qi,F,X; Goodman,S,D; Anderson,M,H; Shi,W,Y. 2003. Mutation of luxS affects biofilm formation in Streptococcus mutans.  INFECTION AND IMMUNITY. Vol. 71, no. 4. (April): 1972-1979.
  • Wang,Y; Goodman,S,D; Redfield,R,J; Chen,C. 2002. Natural transformation and DNA uptake signal sequences in Actinobacillus actinomycetemcomitans.  JOURNAL OF BACTERIOLOGY. Vol. 184, no. 13. (July): 3442-3449.
  • Goodman,S,D; Gao,Q. 2000. Firefly luciferase as a reporter to study gene expression in Streptococcus mutans (vol 42, pg 154, 1999).  PLASMID. Vol. 43, no. 2. (March): 184-184.
  • Goodman,S,D; Gao,Q. 2000. Characterization of the gtfB and gtfC promoters from Streptococcus mutans GS-5.  PLASMID. Vol. 43, no. 1. (January): 85-98.
  • Teter,B; Goodman,S,D; Galas,D,J. 2000. DNA bending and twisting properties of integration host factor determined by DNA cyclization.  PLASMID. Vol. 43, no. 1. (January): 73-84.
  • Wackwitz,B; Bongaerts,J; Goodman,S,D; Unden,G. 1999. Growth phase-dependent regulation of nuoA-N expression in Escherichia coli K-12 by the Fis protein: upstream binding sites and bioenergetic significance.  MOLECULAR AND GENERAL GENETICS. Vol. 262, no. 4-5. (December): 876-883.
  • Lorenz,M; Hillisch,A; Goodman,S,D; Diekmann,S. 1999. Global structure similarities of intact and nicked DNA complexed with IHF measured in solution by fluorescence resonance energy transfer.  NUCLEIC ACIDS RESEARCH. Vol. 27, no. 23. (December): 4619-4625.
  • Goodman,S,D; Kay,O. 1999. Replacement of integration host factor protein-induced DNA bending by flexible regions of DNA.  JOURNAL OF BIOLOGICAL CHEMISTRY. Vol. 274, no. 52. (December): 37004-37011.
  • Goodman,S,D; Gao,Q. 1999. Firefly luciferase as a reporter to study gene expression in Streptococcus mutans.  PLASMID. Vol. 42, no. 2. (September): 154-157.
  • Goodman,S,D; Velten,N,J; Gao,Q,A; Robinson,S; Segall,A,M. 1999. In vitro selection of integration host factor binding sites.  JOURNAL OF BACTERIOLOGY. Vol. 181, no. 10. (May): 3246-3255.
  • Devulpalle,K,S; >b>Goodman,S,D; Gao,Q; HEMSLEY,A; Mooser,G. 1997. Knowledge-based model of a glucosyltransferase from the oral bacterial group of mutans streptococci.  PROTEIN SCIENCE. Vol. 6, no. 12. (December): 2489-2493.
  • Esposito,D; Fitzmaurice,W,P; Benjamin,R,C; Goodman,S,D; Waldman,A,S; Scocca,J,J. 1996. The complete nucleotide sequence of bacteriophage HP1 DNA.  NUCLEIC ACIDS RESEARCH. Vol. 24, no. 12. (June): 2360-2368.
  • Chen,C; Goodman SD. 1995. SPONTANEOUSLY RELEASED BACTERIOPHAGE FROM ACTINOBACILLUS-ACTINOMYCETEMCOMITANS.  JOURNAL OF DENTAL RESEARCH. Vol. 74, no. January: 197-197.
  • Segall,A,M; Goodman,S,D,; Nash,H,A. 1994. ARCHITECTURAL ELEMENTS IN NUCLEOPROTEIN COMPLEXES - INTERCHANGEABILITY OF SPECIFIC AND NONSPECIFIC DNA-BINDING PROTEINS.  EMBO JOURNAL. Vol. 13, no. 19. (October): 4536-4548.
  • Goodman,S,D; Nicholson,S,C; Nash,H,A. 1992. DEFORMATION OF DNA DURING SITE-SPECIFIC RECOMBINATION OF BACTERIOPHAGE-LAMBDA - REPLACEMENT OF IHF PROTEIN BY HU PROTEIN OR SEQUENCE-DIRECTED BENDS.  PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. Vol. 89, no. 24. (December): 11910-11914.
  • Goodman,S,D; Scocca,J,J. 1991. FACTORS INFLUENCING THE SPECIFIC INTERACTION OF NEISSERIA-GONORRHOEAE WITH TRANSFORMING DNA.  JOURNAL OF BACTERIOLOGY. Vol. 173, no. 18. (September): 5921-5923.
  • Goodman SD, Yang CC, Nash HA, Sarai A, and Jernigan R. 1990. Bending of DNA by IHF Protein. In The Sixth Conversation in the Discipline Biomolecular Stereodynamics
  • Goodman,S,D; Nash,H,A. 1989. FUNCTIONAL REPLACEMENT OF A PROTEIN-INDUCED BEND IN A DNA RECOMBINATION SITE.  NATURE. Vol. 341, no. 6239. (September): 251-254.
  • Goodman,S,D; Scocca,J,J. 1989. NUCLEOTIDE-SEQUENCE AND EXPRESSION OF THE GENE FOR THE SITE-SPECIFIC INTEGRATION PROTEIN FROM BACTERIOPHAGE-HP1 OF HEMOPHILUS-INFLUENZAE.  JOURNAL OF BACTERIOLOGY. Vol. 171, no. 8. (August): 4232-4240.
  • Goodman,S,D; Scocca,J,J. 1988. IDENTIFICATION AND ARRANGEMENT OF THE DNA-SEQUENCE RECOGNIZED IN SPECIFIC TRANSFORMATION OF NEISSERIA-GONORRHOEAE.  PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. Vol. 85, no. 18. (September): 6982-6986.
  • Waldman,A,S; Goodman,S,D; Scocca,J,J. 1987. NUCLEOTIDE-SEQUENCES AND PROPERTIES OF THE SITES INVOLVED IN LYSOGENIC INSERTION OF THE BACTERIOPHAGE HP1C1 GENOME INTO THE HAEMOPHILUS-INFLUENZAE CHROMOSOME.  JOURNAL OF BACTERIOLOGY. Vol. 169, no. 1. (January): 238-246.
  • Goodman SD, Yang CC, Nash HA, Sarai A, and Jernigan R. Proceedings of the Sixth Conversation in the Discipline Biomolecular Stereodynamics. Edited by Sarma RH and Sarma MH.
  • Yu H, Lim HH, Tjokro NO, Sathiyanathan P, Natarajan S, Chew TW, Klonisch T, Goodman SD, Surana U, Dröge P. Chaperoning HMGA2 Protein Protects Stalled Replication Forks in Stem and Cancer Cells.  Cell Reports. PubMed ID: 24508460
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