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Don Demuth


 Name: Don Demuth

Title: Professor

Current Position: Acting Associate Dean for Research

Phone:
502-852-3807

E-mail:
drdemu01@louisville.edu

Background

Education and Post_Graduate Training:

1982-1986      Post_Doctoral Fellowship, Wistar Institute, Philadelphia, PA
1976-1982      Ph.D _  Molecular Biology,  Lehigh University, Bethlehem, PA
1972-1976      B.S. _  Biology,  Kutztown State University, Kutztown, PA

Academic Appointments

  • 2009 – present: Associate Dean for Research, ULSD
  • 2003 – present: Professor, Dept. Oral Health & Rehabilitation, University of Louisville School of Dentistry, Louisville, KY
  • Professor, Dept. Microbiol. Immunol., University of Louisville
  • School of Medicine, Louisville, KY (Joint Appointment)
  • 2003- present: University Scholar, University of Louisville, Louisville, KY
  • 2001-2003: Associate Professor of Biochemistry, University of Pennsylvania, School of Dental Medicine, Philadelphia, PA.
  • 1995 - 2001: Research Associate Professor,  Department of Biochemistry, University of Pennsylvania School of Dental Medicine, Philadelphia, PA.
  • 1989-1995: Research Assistant Professor,  Department of Biochemistry, University of Pennsylvania School of Dental Medicine, Philadelphia, PA.
  • 1986-1989: Research Associate, Department of Biochemistry, University of Pennsylvania School of Dental Medicine, Philadelphia, PA.



Non-Academic Positions

  • 1999 - 2003: Scientific Advisor, Schnader, Harrison, Segal & Lewis, attnys., Intellectual Property Department, Philadelphia, PA.
  • 1986 - 1999: Biotechnology Consultant; Weiser & Associates, Patent, Trademark and Copyright Attorneys, Philadelphia, PA.


Research Interests and Current Projects
To colonize and persist in a host, bacterial pathogens must first adhere tightly to tissue surfaces and evade or overcome the host immune response as well as various non-immune anti-microbial activities.  Our studies focus on the mechanisms used by pathogens to accomplish these tasks and we utilize the complex microbial community of the human oral cavity as a model to study these processes.  We are investigating the mechanism of action of several protein toxins produced by oral pathogens.  These proteins target human immune cells, e.g., macrophages, neutrophils and lymphocytes, and our goal is to understand the role that these toxins play in actively avoiding the immune response during infection.  Organisms may also passively avoid the immune response by growing as a biofilm.  We are interested in determining how oral pathogens identify a suitable niche and colonize the complex microbial community that exists in the oral cavity.  The long term goal of these studies is to design novel therapeutics that target oral pathogens and prevent their colonization of the dental biofilm.  The development and growth of complex microbial communities may also require communication among the cells within the biofilm and we are investigating mechanisms of bacterial cell-to-cell communication, focusing on quorum sensing systems that are present in oral pathogens.  The goal of these studies is to determine if quorum sensing plays a role in allowing organisms to sense and respond to their local environment and the other bacteria that cohabit that environment.

Current Projects
The periodontal pathogen P. gingivalis colonizes the pre-existing oral biofilm by interacting with a surface protein (SspA) expressed by all oral streptococci.  However, P. gingivalis selectively adheres to the viridans streptococci and not mutans streptococci.  We have identified a discrete motif of SspA that is involved in this interaction.  Using a protein engineering approach, we are investigating the specific protein structure that is recognized by P. gingivalis in order to generate peptide mimetic compounds that may block P. gingivalis colonization of the oral cavity.
 
The gene responsible for the production of the auto-inducer 2 signal (AI-2) is conserved in many bacteria, yet whether it plays a role in cell-to-cell communication in all organisms remains controversial.  We are interested in determining the level of specificity in cell-to-cell communication mediated by AI-2 and in identifying the cellular components that are involved in AI-2 signal transduction in oral pathogens.  The ultimate goal is to determine if quorum sensing is a viable target for therapeutic intervention of biofilm-mediated diseases.

Cigarette smoking often increases the severity of periodontal disease and components in smoke are known to affect aspects of the human innate immune response.  However, little is known about how components in cigarette smoke affect the oral pathogens that initiate periodontitis.  Our results show that P. gingivalis gene expression is dramatically altered upon exposure to smoke extracts and many of the differentially expressed genes are associated with its virulence or interaction with host tissues.  Our goal is to determine if these smoke-induced changes in microbial gene expression and physiology contribute to the increased severity of disease in smokers. This may lead to novel methods to control periodontitis in these patients.


Teaching Activities

  • 2003–present: University of Louisville School of Medicine, Microbial Pathogenesis MBIO687, Dept. Microbiol & Immunol. - 3 lecture hours per semester
  • 2003–present: University of Louisville School of Medicine, Molecular Microbiology MBIO601, Dept. Microbiol & Immunol. - 3 lecture hours per semester
  • 2004-present: University of Louisville School of Medicine, Dept Microbiol & Immunol Journal Club.  Team taught weekly literature presentations.
  • 2003–present    University of Louisville School of Dentistry, Correlated Sciences in Dentistry, 1 lecture hour
  • 2006-present    University of Louisville School of Dentistry, Oral Microbiology for Residents, 3 lecture hours



Service

  • 2009-present: Chair, Delta Dental Professorship Search Committee
  • 2008: Distinguished Faculty Committee, ULSD
  • 2008: Dept. Microbiology/Immunology Search Committee, UofL SOM
  • 2008-present: Academic Programs Committee, UofL
  • 2007-08: Chair, Research Misconduct Committee UofL
  • 2006-present: Center & Institute Review Committee, UofL
  • 2006-present: Faculty Senator, University of Louisville
  • 2006-present: Steering Committee, Research!Louisville, University of Louisville HSC
  • 2005-present: Faculty Personnel Committee, University of Louisville School of Dentistry
  • 2005, 2006: Dean Search Committee, University of Louisville School of Dentistry
  • 2004-present: Director, Summer Research Program, University of Louisville School of Dentistry
  • 2004-2006: Distinguished Faculty Committee, University of Louisville School of Dentistry.
  • 2003-present: Environmental Committee, University of Louisville School of Dentistry.


Memberships

  • 1990 - present: American Association for Advancement of Science
  • 1994 - present: American Society  for Microbiology
  • 2002 - present: International Association of Dental Research


Honors and Awards (Top 3-5)

  • Associate Editor – Microbiology   2010 - present
  • President’s Distinguished Faculty Award – School of Dentistry Nominee 2009
  • Senator, University of Louisville Faculty Senate, 2006 - present
  • Editorial Board, Infection and Immunity, 2004 - present
  • University Scholar, University of Louisville, 2003 - present


Publications (last 5 years)

 

Juárez-Rodríguez, M.D., Torres-Escobar, A. and Demuth, D.R.  2013.  Construction of new cloning, lacZ reporter and scarless-markerless suicide vectors for genetic studies in Aggregatibacter actinomycetemcomitans.  Plasmid.  In press.

 

Torres-Escobar, A., Juárez-Rodríguez, M.D.,  Lamont, R.J. and Demuth, D.R.  2013 Transcriptional regulation of Aggregatibacter actinomycetemcomitans lsrACDBFG and lsrRK operons and their role in biofilm formation.  J. Bacteriol.  195:56-65.

 

Hirano, T., Beck, D.A.C., Wright, C.J., Demuth, D.R., Hackett, M. and Lamont, R.J.  2012.  Regulon controlled by the GppX hybrid two component system in Porphyromonas gingivalis.  Molec. Oral Microbiol.  In press.

 

Hirano, T., Beck, D.A., Demuth, D.R., Hackett, M. and Lamont, R.J.  2012.  Deep sequencing of Porphyromonas gingivalis and comparative transcriptome analysis of a luxS mutant.  Front. Cell Infect. Microbiol.   2:79.

 

Loner, C.M., Luzzio, F.A. and Demuth, D.R.  2012.  Preparation of azidoaryl- and azidoalkyloxazoles for click chemistry.  Tetrahedon Lett.  53:5641-5644.

 

Umeda, J.E., Demuth, D.R., Ando, E.S., Faveri, M. and Mayer, M.P.A.  2012.  Signaling transduction analysis in gingival epithelial cells after infection with Aggregatibacter actinomycetemcomitans.  Molec. Oral Microbiol.  27:23-33.

 

Bagaitkar, J., Renaud, D.E., Demuth, D.R. and Scott, D.A.  2011.  Tobacco smoke augments Porphyromonas gingivalis – Streptococcus gordonii biofilm formation. PLoS ONE 6(11): e27386. doi:10.1371/journal.pone.0027386.

 

Daep, C.A., Novak, E.A., Lamont, R.J. and Demuth, D.R.  2011.  Structural dissection and in vivo effectiveness of a peptide inhibitor of Porphyromonas gingivalis adherence to Streptococcus gordonii.  Infect. Immun.  79:67-74.

 

Chawla, A., Hirano, T., Bainbridge, B.W., Demuth, D.R., Xie, H., and Lamont, R.J.  2010.  Community signaling between S. gordonii and P. gingivalis is controlled by the transcriptional regulator CdhR.  Mol. Microbiol. 78:1510-1522.

 

Daep, C.A., Novak, E.A., Lamont, R.J. and Demuth, D.R.  2010.  Selective substitution of amino acids limits proteolytic cleavage and improves the bioactivity of an anti-biofilm peptide that targets the periodontal pathogen, Porphyromonas gingivalis.  Peptides.  31:2173-2178.

 

Bagaitkar, J., Demuth, D.R., Daep, C.A., Renaud, D.E., Pierce D.L., and Scott, D.A.  2010.  Tobacco Upregulates P. gingivalis Fimbrial Proteins Which Induce TLR2 Hyposensitivity. PLoS ONE 5(5): e9323. doi:10.1371/journal.pone.0009323

 

Novak, E.A., Shao, H., Daep, C.A. and Demuth, D.R.  2010.  Autoinducer-2 and QseC control biofilm formation and in vivo virulence of A. actinomycetemcomitans.  Infect. Immun.  78:2919-2926.

 

Shao, H. and Demuth, D.R.  2010.  Quorum sensing regulation of biofilm growth and gene expression in oral bacteria and periodontal pathogens.  Periodontol. 2000  52:53-67.

 

Pierce, D.L., Nishiyama, S., Liang, S., Wang, M., Triantafilou, M., Triantafilou, K., Yoshimura, F., Demuth, D.R., and Hajishengallis, G.  2009.  Host adhesive activities and virulence of novel fimbrial proteins of Porphyromonas gingivalis.  Infect. Immun. 77:3294-3301.

 

Rabin, S.D.P., Flitton, J.G. and Demuth, D.R.  2009.  Aggregatibacter actinomycetemcomitans cytolethal distending toxin induces apoptosis in non-proliferating macrophages by a phosphatase independent mechanism.  Infect. Immun. 77:3161-3169.

 

Shao, H. and Demuth, D.R.  2010.  Quorum sensing regulation of biofilm growth and gene expression in oral bacteria and periodontal pathogens.  Periodontol. 2000  52:53-67.

 

Pierce, D.L., Nishiyama, S., Liang, S., Wang, M., Triantafilou, M., Triantafilou, K., Yoshimura, F., Demuth, D.R., and Hajishengallis, G.  2009.  Host adhesive activities and virulence of novel fimbrial proteins of Porphyromonas gingivalis.  Infect. Immun. 77:3294-3301.

 

Rabin, S.D.P., Flitton, J.G. and Demuth, D.R.  2009.  Aggregatibacter actinomycetemcomitans cytolethal distending toxin induces apoptosis in non-proliferating macrophages by a phosphatase independent mechanism.  Infect. Immun. 77:3161-3169.

 

Bagaitkar, J., Williams, L.R., Renaud, D.E., Bemakanakere, M.R., Scott, D.A. and Demuth, D.R. 2009.  Tobacco-induced alterations to Porphyromonas gingivalis-host interactions.  Environ. Microbiol.  11:1242-1253.

 

Bagaitkar, J., Demuth, D.R. and Scott, D.S.  2008.  Tobacco use and susceptibility to bacterial infection.  Tobacco Induced Diseases 4: 12-19.

 

Gorr, S-U., Sotsky, J.B., Shelar, A.P. and Demuth, D.R.  2008.  Design of bacteria agglutinating peptides derived from parotid secretory protein, a member of the PLUNC  family of BPI-like proteins.  Peptides 29:2119-2127.

Hajishengallis, G., M. Wang, S. Liang, M.A. Shakhatreh, D. James, S.-I. Nishiyama, F. Yoshimura, and D.R. Demuth.  2008.  Subversion of innate immunity by periodontopathic bacteria through exploitation of complement receptor-3.  In: J.D. Lambris (ed.), Current Topics of Complement II. Adv. Exp. Med. Biol. 632:203-215.

 

Rajendran, N., Rajnarayanan, R.V. and Demuth, D.R.  2008.  Molecular phylogenetic analysis of tryptophanyl-tRNA synthetase of Actinobacillus actinomycetemcomitans.  Z. Naturforsch. 63c:418-428.

 

Daep, C.A., Lamont, R.J. and Demuth, D.R.  2008.  Interaction of Porphyromonas gingivalis with oral streptococci requires a motif that resembles the eukaryotic nuclear receptor box protein-protein interaction domain.  Infect. Immun.  76:3273-3280.

 

Maeda, K., Tribble, G.D., Tucker, C.M., Anaya, C., Shizukuishi, S., Lewis, J.P., Demuth, D.R. and Lamont, R.J.   2008.  A Porphyromonas gingivalis tyrosine phosphatase is a multifunctional regulator of virulence attributes.  Mol. Microbiol. 

 

Capestany, C.A., Tribble, G.D., Maeda, K., Demuth, D.R. and Lamont, R.J.  2008.  Role of the Clp system in stress tolerance, biofilm formation and intracellular invasion in Porphyromonas gingivalis.  J. Bacteriol.  190:1436-1446.

 

Schaeffer, L.M., Schmidt, M.L. and Demuth, D.R.  2008.  Induction of Aggregatibacter actinomycetemcomitans Leukotoxin Expression by IS1301 and orfA.  Microbiol.  154:528-538.

  
Book Chapters

 

Book Chapters
  • D.R. Demuth and R. J. Lamont.  2007.  Quorum sensing and cell-to-cell communication in the oral biofilm.  In Bacterial Cell-to-Cell Communication: Role in Virulence and Pathogenesis.  Donald R. Demuth and Richard J. Lamont, eds.  Cambridge University Press, Cambridge, U.K. 
  • H.J. Shao and D. R. Demuth.  2008.  Quorum Sensing as a means of biofilm communication.  In Periodontal Medicine and Systems Biology.  Brian Henderson and Mike Curtis, Robert Seymour and Nikos Donos Eds.  Blackwell Publishing, Oxford, U.K.  in press.



Books
Bacterial Cell-to-Cell Communication: Role in Virulence and Pathogenesis.  2007.  Donald R. Demuth and Richard J. Lamont, eds.  Cambridge University Press, Cambridge, U.K. 



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