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      Research Interests

      For more information visit the Valvano lab home page http://publish.uwo.ca/~mvalvano/

      Valvano Lab Mission Statement

      • To carry out hypothesis-driven research in microbiology
      • To train graduate students and postdoctoral fellows to become outstanding biomedical scientists
      • To develop and foster an environment of scientific inquiry, and at the same time respect for each individual's expertise and contribution
      • To place an emphasis on personal and scientific integrity and on team player skills

      Research Statement

      What do we do?

      Our research involves an interdisciplinary approach using molecular genetics, biochemistry, cell biology, and structural biology to understand the pathogenesis of Gram-negative bacteria at the molecular level. Burkholderia cenocepacia, Escherichia coli, Salmonella enterica, and Shigella flexneri are the model organisms we use in different aspects of our research program.

      Why is it important?

      Opportunistic infections pose a significant threat to human health, especially to those patients who benefit most from advancements in the treatment of genetic diseases, cancer, and organ transplantation, but who become immunosuppressed.

      Burkholderia cepacia complex bacteria (Bcc) and Burkholderia cenocepacia in particular are our main model organisms to study the pathogenicity of opportunistic bacteria. Bcc bacteria are a major health risk for children and young adults with genetic conditions like cystic fibrosis and chronic granulomatous disease.

      These patients commonly suffer from lung and airways infections by these microorganisms, which are very difficult to treat given the extraordinary resistance of these bacteria to clinically useful antimicrobials. Therefore, through out research we hope to find novel ways to prevent or ameliorate the effect of these infections in susceptible patients.

      Enteric bacteria such as Escherichia coli, Salmonella, and Shigella are also important human pathogens, which are particularly endemic in certain parts of the world.

      Lipopolysaccharide (LPS) is a complex glycolipid molecule located on the surface of Gram negative bacteria that is also a critical structural component of the bacterial outer membrane. Bacteria with defects in the LPS molecule are more sensitive to a variety of antibiotics and they can be easily killed by host defensive mechanisms such as the serum complement and antimicrobial peptides.

      Therefore, by understanding how the LPS is made and assembled on the bacterial cell surface we hope to design inhibitors that will interfere with this process, which may be useful as novel antimicrobials. Also, we are looking at ways to alter LPS biosynthesis at various levels to increase the overall permeability of the outer membrane to antibiotics and antimicrobial peptides.

      What we learn in Escherichia coli, Salmonella enterica, and Shigella flexneri is also applied to Burkholderia cenocepacia.

      Examples of key questions we currently investigate

      We discovered that genetic ablation of LPS synthesis or chemical inhibitors of certain LPS biosynthesis enzymes can "weaken" the bacterial outer membrane and facilitate the entry of conventional antibiotics and antimicrobial peptides, especially in B. cenocepacia and other Bcc bacteria. We have also conducted detailed studies on proteins required for the synthesis of core oligosaccharide and O antigen moieties of the LPS molecules. These components are crucial for the virulence of E. coli, Salmonella, and Shigella. Now we want to learn:

      How LPS components are synthesized?
      What are the mechanistic bases of the translocation of O-antigen LPS biosynthesis intermediates across the plasma membrane?
      How Bcc bacteria can survive the attack of antimicrobial cationic peptides and other antibiotics?

      We discovered that Bcc bacteria survive intracellularly in free-living amoebae and macrophages by altering the maturation of the phagosome, and this research has led to the hypothesis that these cells become a reservoir for the persistence and dissemination of these bacteria in the host. We have also discovered a novel secretory system in B. cenocepacia (type VI) that appears to alter the cytoskeleton of infected macrophages and is required for infection in an animal model of chronic lung infection. Now we want to learn:

      How does intracellular B. cenocepacia delay phagosome maturation and phagosomal acidification?
      What is the role of a novel type 6 secretion system in B. cenocepacia intracellular survival?
      How does intracellular B. cenocepacia affect the assembly of the macrophage NADPH oxidase?

      We discovered several master regulators that respond to different types of stress. Mutations in the genes encoding these regulators impair the ability of B. cenocepacia to survive within macrophages and also in the animal model of chronic lung infection. We have observed that antioxidant bacterial defenses are critical for intracellular survival. Now we want to learn:

      How does B. cenocepacia adapt to various environments including macrophage and epithelial cells?
      What are the roles of stress regulators in intracellular survival and in bacterial survival in the rat model of chronic lung infection?
      How do bacterial antioxidant mechanisms protect essential bacterial metabolic pathways that are deemed to be critical for adaptation to different environments, including the lung and airways?

      Sometimes genetic tools are not available for our specific research needs. Therefore, we place special effort in developing new tools and reagents or modifying those available to our own needs. In particular, our lab has contributed novel molecular tools to handle Bcc bacteria.

      Achievements and Distinctions

      • Zeller Senior Scientist Award, in recognition to outstanding contributions to Cystic Fibrosis Canada as an established investigator. 2011.
      • Certificate of Recognition for outstanding service as an online mentor of the ASM Minority Mentorship Program, American Society for Microbiology. 2011
      • Tier I Canada Research Chair in Infectious Diseases and Microbial Pathogenesis. 2009-2016 (resigned in 2012 to take Chair at Queen's University).
      • Senior Scientist, Research Training Award, Canadian Cystic Fibrosis Foundation. 2009
      • CSM/Roche Award, Canadian Society of Microbiologists, given to outstanding Canadian microbiologists.
      • Dean’s Award of Excellence for outstanding contributions, Schulich School of Medicine and Dentistry, UWO. 2006
      • Certificate of Excellence in Undergraduate Medical Education for the Infection and Immunity block in 1st year, Hippocratic Council Undergraduate Medical Education Committee, Schulich School of Medicine and Dentistry. 2005
      • Tier I Canada Research Chair in Infectious Diseases and Microbial Pathogenesis. 2002-2009
      • Honour's Degree for Academic Excellence, School of Medicine, University of Buenos Aires (Academic Cumulative Average of 91.5 %).

      Teaching

      Queen's University (current)

       

      Postdoctoral Research Assistant

      S-Q. An, 2017-

       

      Post-Graduate Students

       

      Primary Supervisor:

      S. Keenan, MRes Translational Medicine, QUB, 2016-17.

      S. Paterson, MSci Biochemistry, QUB, 2016-17.

      M. NaGuib, MSc (Alexandria University, Egypt), PhD Student, 2015-18.

      F. Bisaro, PhD Student, 2015-18.

       

      Second Supervisor:

      H. Carrasco, PhD Student, 2014-17.

      D. Storey, PhD Student, 2016-19.

       

      Honour’s Students

      S. Carson, 2016-17.

       

      Past Trainees

       

      Research Associates

      QUB:

      J. Torres-Bustos, Research Assistant, 2012-16.

       

      UWO:

      K. Nurse, Research Technician, 2010-15.

      W. Cladman, Research Technician, 2010.

      A. Roa-Rosales, Research Technician, 2008-09.

      C. James, PhD, Research Technician, 2008.

      J. Lehrer, MSc Research Technician, 2006.

      D. Stoykova, Research Technician, 2005-06.

      S. Loutet, Research Technician, 2003-04.

      K. Vigeant, Research Technician, 2003-04.

      L. Santamaria, Research Technician, 2003.

      J. Vicarioli, Research Technician, 2002-03.

      L. Dafoe, Research Technician, 1989-96.

      C.L. Marolda, Biochemist, Research Associate, 1988-10.

       

      Visiting International Researchers

       

      QUB:

      J. Ramos Vivas, Researcher, IDIVAL, Santander, Spain, Sep 2016.

       

      MSc Students

      QUB:

      D. Guerreiro, (University of Lisbon), MSc Student 2015-16.

      S. O'Brien, MRes student in Translational Medicine, Sep 2013 - Aug 2014.

      S. Chakravarty, MRes student in Translational Medicine, Sep 2013 - Aug 2014.

      T. Schmidt, MSc Diploma Thesis, Free University of Berlin, Sep 2013 - Mar 2014

       

      UWO:

      S. Lamothe, B.Sc. (UWO), MSc Student, 2011-13.

      H. Ostapka, B.Sc. (UWO), MSc Student, 2010-13.

      M. Alati, Visiting MSc (Department of Biotechnology, University of Milano-Biccoca), Sep-Dec 2011.

      C. Clarke, B.Sc. (Guelph), MSc Student, 2009-11.

      A. Skeldon, B.Sc. (Toronto), MSc Student, 2008-10. Supported by a CIHR award.

      D. Hynes, B.Sc. (Queen’s), MSc Student, 2007-09. Supported by a CCFF award.

      R. Newman, B.Sc. (UWO), MSc Student, 2007-09.

      J. Haggerty, B.Sc. (UWO), MSc Student, 2006-08. M&I entrance Award winner.

      M. McGarry, B.Sc. (University of Western Ontario), MSc student, 2004-07. Supported by an OGS award.

      P. Lahiry, B.Sc. (University of Waterloo), MSc student, 2005-06. Supported by a CIHR Canada Graduate award.      

      J. Lehrer, B.Sc. (Concordia University), MSc student, 2003-05.     

      K. Vigeant, B.Sc. (University of Guelph), MSc student, 2001-03.

      R. Flannagan, B.Sc. (UWO), MSc student (co-supervised with Dr. S. F. Koval), 2000-02-. Supported by an NSERC PGSA award.

      R. Payne, B.Sc. (University of Southern California), MSc student, 1999-02.

      L. Singh (Saini), B.Sc. (University of Guelph), MSc Student, 1996-99.

      M. Bittner, B.Sc. (Faculty of Chemical and Pharmaceutical Sciences, University of Chile). Visiting student, October-December 1997.

      J. Gaspar, B.Sc. (University of Waterloo), MSc Student, 1994-97.

      M. Grattan, B.Sc. (UWO), MSc Student (Co-supervised with A. Ridgway), 1991-92.

       

      PhD Students

      QUB:

      A. Ford, PhD Student, 2013-16.

      Y. Fathy, MSc (Alexandria University, Egypt), PhD Student, 2013-16.

      J. Roszkowiak, Visiting PhD Student, Wroclaw University, Sep-Dec 2015

      R. Maldonado, Visiting PhD Student, Portugal, Feb-Aug 2014

      L. Kalferstova, Visiting PhD Student, Prague, Sep-Nov, 2014.

      R. Dennehy, (Institute of Technology, Tallaght, Dublin), Visiting Student, Oct-Nov 2012.

       

      UWO:

      M. Khodai-Kalaki, MSc (UWO), 2011-15.

      O. El-Halfawy, MSc (Alexandria University, Egypt), 2010-14. Supported by OGS award

      S. Furlong, B.Sc. (UWO), 2008-13 -. Supported by OGSST and OGS awards.

      Y. Fathy, MSc (Alexandria University, Egypt), Visiting PhD Student, 2012.

      A. Valderrey, Visiting PhD student (Department of Microbiology II, Universidad Complutense de Madrid, Spain), Apr-Jul 2012.

      J. Tolman, B.Sc. (Carlton), 2006-11. Supported by NSERC and CCFF awards; M&I entrance Award winner.

      K. Patel, B.Sc. (University of Waterloo), 2005-10. Supported by OGSST award.

      A. Valderrey, Visiting PhD student (Department of Microbiology II, Universidad Complutense de Madrid, Spain), Jan-Apr 2011.

      M. Al Zayer, MSc (Texas), 2010-11.

      S. Loutet, B.Sc. (University of British Columbia), 2004-10. Supported by NSERC award; M&I entrance Award winner.

      A. Hoare, Biochemist (University of Chile), (co-supervised with Dr. I. Contreras), 2006-10.

      D. Bravo, Biochemist (University of Chile), (co-supervised with Dr. I. Contreras), 2006-09.

      K. Maloney, B.Sc. (UWO), 2002-08; Supported by CCFF award.

      E. Lameignere, PhD (Université Joseph Fourier, Grenoble, France), Visiting PhD student, 2007.

      R. Flannagan, MSc (UWO), 2003-07. Supported by OGSST and CCFF award; M&I entrance Award winner; 2006 John A. Thomas Award winner.

      J. Lamothe, B.Sc. (Laval University), 2002-07. Supported by CCFF and CIHR doctoral Canada Graduate Award; Present position: Supervisor Microbiology, Zimmer Dental, San Diego, California.

      S. Sarnacki, B.Sc. (University of Buenos Aires), Visiting PhD student, 2005-06.

      F. McArthur, MSc (Mt. Allison University), 2000-05. Supported by OGSST award; Present position: Laboratory Group Leader - Microbiology, Durham Regional Environmental Laboratory, Ontario.

      M. Novoa-Garrido, visiting PhD Student, Norwegian Veterinary College, Feb 2004/Feb 2005.Present position: Researcher, BioForsk Nord, Bodø, Norway.

      S. Saldías, Biochemist (University of Chile), (co-supervised with Dr. I. Contreras) 2001-04.

      E. Vinés, Biochemist (University of Chile), 2000-04; Present position: Professor, University Andrés Bello, Viña del Mar, Chile

      M. Lefebre, B.Sc. (UWO), 1998-04. Supported by NSERC PGSA and CIHR Doctoral awards; nominated for the Collip Medal Award, Stephen D. Poland Award winner.

      T. A. Hunt, MSc (University of Calgary), 2000-03. Supported by CCFF award; Present position: Assistant Professor, Kansas Medical School, Kansas City.

      A. Amer, MD, MSc (Cairo University), PhD Student, 1997-02. Supported by OGS Award. Present position: Associate Professor, Division of Pulmonary, Allergy, Critical Care & Sleep Medicine, Ohio State University, Columbus, Ohio.

      M. Feldman, B.Sc. (Institute of Biochemistry, Fundación Campomar, Argentina). Visiting PhD student, May-July, 1997/Aug-Sep,1998. Present position: Associate Professor, Department of Molecular Microbiology, Washington University, St. Louis, USA.

      A. Bouchet (Institut Gustave-Roussy, Villejuif, France) Visiting PhD Student, January-May 1993.

      J. S. Brooke, MSc (UWO), 1992-96. Supported by OGS and NSERC awards. Award winner: Graduate Student Award, Canadian Society of Microbiologists, 1995. Present position: Associate Professor, Department of Biology, DePaul University at Chicago.

      A. Thariath, MSc (Chemistry, University of Waterloo), Visiting PhD student, June-August 1991. Present position:Director of Product Development, Cytovax Biotechnologies, Inc., Edmonton, AB.

      J. A. Thomas, D.V.M. (University of Guelph), 1990-94. Award winner: Graduate Student Award, Canadian Society of Microbiologists, 1992; Supported by an OGS Award. Deceased December 1993.

       

      Fellows

      QUB:

      C. Mujica, PhD (University Andres Bellow, Chile), Postdoctoral Research Assistant, 2012-15.

      E. Perrin, PhD (University of Florence), Visiting Fellow (FEMS Award), 2015.

      G. Pradenas, PhD (Univ. of Santiago de Chile, Chile), Postdoctoral Research Assistant, 2013-15.

      K. Patel, PhD (University of Western Ontario), Postdoctoral Research Assistant, 2012-14.

      A. Hanuszkiewicz, PhD (University of Borstel, Germany), Postdoctoral Research Assistant, 2012-14.

       

      UWO:

      O. El-Halfawy, MSc (Alexandria University, Egypt), PhD (UWO), Postdoctoral Fellow, 2014-15.

      F. Tavares, PhD (University of Mexico), 2012-15.

      A. Andrade, PhD (University of Mexico), 2011-15. Present position:AssistantProfessor, Monterrey, Mexico.

      X. Ruan, PhD (Tsinghua University), 2008-14.

      C. Schmerk, PhD (University of Victoria), Supported by a Fellowship from Cystic Fibrosis Canada. 2010-14.

      D. Aubert, PhD (University of Paris), Supported by a Fellowship from CIHR. 2005-13.

      M. Hamad, Ph.D (University of Nebraska), 2008-13.

      K. Patel, PhD (University of Western Ontario), 2012.

      C. Mujica, PhD (University Andres Bellow, Chile), 2011-12.

      A. Hanuszkiewicz, PhD (University of Borstel, Germany), 2009-12.

      R. Rosales-Reyes, PhD (University of Mexico), 2009-12. Present position:Professor, Universidad Autónoma de Mexico.

      S. Saldías, PhD, Biochemist (University of Chile), 2007-11. Supported by a Fellowship from the Canadian Cystic Fibrosis Foundation

      S. Loutet, PhD (University of Western Ontario), Supported by a Fellowship from CIHR. 2010-11.

      X. Ortega-Alonso, PhD (University of Chile), 2002-08. Present position: Professor, University Andrés Bello, Viña del Mar, Chile.

      J. Perez-Donoso, PhD (University of Santiago, Chile), 2007-08. Present position: Associate Professor, Universidad Andres Bello, Chile.

      Karen Keith, PhD (Imperial College, U.K), 2004-08; Supported by a Fellowship from the Canadian Cystic Fibrosis Foundation.

      S. Cardona, PhD (University of Chile), Supported by a Fellowship from the Canadian Cystic Fibrosis Foundation. 2002-06. Present position: Associate Professor, Department of Microbiology, University of Manitoba.

      L. Tatar, PhD (University of Missouri at Kansas City), 2002-06. Present position: Teaching Instructor, Dalhousie University, Halifax, Nova Scotia.

      S. Alvarez, PhD, Lecturer (University of Chile), Visiting Fellow, 2005.

      M. Lefebre, PhD (UWO), 2004.

      C. Fehlner-Gardiner, PhD (University of Western Ontario), 1998-2000. Supported by a Fellowship from the Canadian Cystic Fibrosis Foundation. Present position: Research Scientist, Animal Diseases Research Institute, Canadian Food Inspection Agency, Ottawa.

      F-S. Wang, PhD (Pennsylvania State University), 1997-99.

      M.I. Fernández, Clinical Microbiologist, Visiting Fellow (Instituto Argentino del Diagnóstico, Buenos Aires, Argentina, 1997.

      Z. Yao, MSc (University of Beijing), Visiting Fellow.  1991-93. 

      M. Handelsman, PhD (University of Guelph), 1990-92. Supported by a Postdoctoral Fellowship from the Ontario Ministry of Health. 

       

      International Visiting Undergraduate Students

      QUB:

      V. Peña Blanque, Universidad Complutense de Madrid (Erasmus), Feb-Sep 2016; B. Bathabure, Universidad Andres Bello, Chile, Apr-Jul 2016; A. Zurita-Guisado, Universidad Complutense de Madrid (Erasmus), Feb-Aug 2015; W-C Soon, University of Singapore, Mar-Jun 2015; L. Daille, MSc, University Andres Bello, Chile, Nov 2012 - Feb 2013;

       

      UWO:

      L. Albarnez, University of Valparaiso, Chile, May 2010-Sep 2011; X. Fernandez, University of Chile, Jan 2011-March 2011.

       

      4th Year Honor’s Theses

      QUB: N. Thompson, 2015-16; C. Brown, 2015-16; K. Dadswell, 2014; C. Doherty, 2014; C.  Connolly, 2013.

       

      UWO: S. Kim, 2013; A. Zandvakili, 2010-11; K. MacDonald, 2008-09; A. Jiwani, 2008-09; L. Mussen, 2007-08; S. Furlong, 2007-08; M. Lung, 2006-07; R., Wu, 2005-06; A. Polichuk, 2005-06; E. Haggerty, 2005-06; J. Tolman, Carleton University, 2005; A. Petersen, 2004-05; D. VanLeewen, 2004-05; J. Gagliardi, 2002-03; K. Maloney, 2001-02; J. Olenick, 2000-01; E. Dunn, 2000-01; T. Hopkins, 1999-00 (Governor's General Medal); S-L. Chang, 1999-00; J. Stephens, 1999-00 (co-supervised with Dr. E. Cairns; T. Chappell, 1998-99; M. Lefebre, 1997-98; S. Hota, 1997-98; P. Hanifi, 1996-97; M. Glaskin-Clay, 1995-96; S. Valiquet, 1995-96 (Gold Medal Award Winner; NSERC Studentship Award); S. MacMillan, 1994-95; W. Kalair, 1994-95; D. Alexander, 1993-94 (Gold Medal Award Winner; MRC Studentship Award); J. Cruthers, 1992-93; J. Welsh, 1989-90 (Honors in Biology); B. Lott, 1989-90; J. Jordan, 1988-89.

       

      BSc. Intercalated Medical Students

      QUB:

      B. Kevin (Wolfson Award), 2013; L. Burns, 2013.

       

      3rd Year Research Projects

      UWO:

      C. Mueller, Sep 01-Apr 02; T. L. Simon, Oct 1996-Feb 1997; N. Hunter, Mar 1995; S. Valiquet, Mar 1995.

       

      Summer Students

      QUB:

      N. Osborne (2015); J. French (2015); S. O'Sullivan, Biochemical Society Summer Vacation Studentship (2014); E. Kavanagh, CII Summer Research Scholarship (2014); R. Medialdea (2013); J. Thompson (2013); C. Connolly (2013); Kilian Schütt (2013);

       

      UWO:

      R. Joseph, NSERC summer studentship (2011); S. Hu, NSERC summer studentship (2010); S. Hu, Canadian Cystic Fibrosis Foundation summer studentship (2009); M. Yang (2008); B. Li, NSERC summer studentship (2007); B. Li, NSERC summer studentship (2006); M. Lung, NSERC summer studentship (2006); L. Killip, Canadian Cystic Fibrosis Foundation summer studentship (2006); C. Bates, Canadian Cystic Fibrosis Foundation summer studentship (2006); M. Lung, NSERC summer studentship (2005); J. Tolman, NSERC summer studentship (2005); R. Wu (2005); A. Balachandran (2004); D. Wehlam, Canadian Cystic Fibrosis Foundation summer studentship (2003); C. Bhat, NSERC summer studentship (2003); C. de Lasa (2003); C. Mueller, NSERC summer studentship (2001-2002); V. Soo, Hargreaves summer studentship award (2000); K. McGibney, NSERC summer studentship (2000); A. Milos, NSERC Summer studentship (1999); J. Wiggins (1999); H. Georgiou (1999); S. Hota (1996; 1997); P. Hanifi, Canadian Cystic Fibrosis Foundation summer studentship (1996); S. Valiquet, Canadian Cystic Fibrosis summer studentship (1995); M. Gajewski, Meds '97 Summer Res. Training Program (1994/1995); T. Kappos, Meds '92 Summer Res. Training Program (1989/1990); J. Welsh (1989).

       

      High-School Students

      QUB:

      C. Fernandez-Llamera, Methodist College Belfast, Jul 1-29, 2016; P. Magee, Tonbridge School, Kent, England, Jun 27-29, 2016.

       

      UWO:

      C. Belchamber, London Central High School (2011); C. Yang, Lucas High School, Bronze Medal in the International Science Fair representing Canada (2008), $200,000 scholarship in 2010 to attend Cambridge University, UK; M. O'Reilly (1998); D. Malpage (1997); J. McIntyre (1996); M. O’Neill (1995); K. Vallas (1993); N. Moon (1992); M. Clark (1991); M. Korvamaker (1990); M. McIntosh (1989).

      Other

      Frequent Journals

      • Journal of Bacteriology

        ISSNs: 0021-9193

        American Society for Microbiology

        Scopus rating (2016): SJR 1.908 SNIP 0.884

        Journal

      • Microbiology (United Kingdom)

        ISSNs: 1350-0872

        Additional searchable ISSN (Electronic): 1465-2080

        Society for General Microbiology

        Scopus rating (2016): SJR 0.805 SNIP 0.648

        Journal

      • Infection and Immunity

        ISSNs: 0019-9567

        American Society for Microbiology

        Scopus rating (2016): SJR 1.997 SNIP 0.914

        Journal

      • Journal of biological chemistry

        ISSNs: 0021-9258

        Additional searchable ISSN (Electronic): 1083-351X

        American Society for Biochemistry and Molecular Biology Inc.

        Scopus rating (2016): SJR 2.755 SNIP 1.125

        Journal

      • Molecular Microbiology

        ISSNs: 0950-382X

        Wiley-Blackwell

        Scopus rating (2016): SJR 2.543 SNIP 0.99

        Journal

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      Contribution to conference papers, events and activities

      ID: 61378