Faculty Profile

Address
630 W. 168th Street

PH-7E-110

New York, NY 10032

Phone.212-342-5244
Fax. 212-305-9313

sl2385@columbia.edu

Affiliations

Division of Periodontics

Center for Interdisciplinary Research on Antimicrobial Resistance

Research Summary

Our main research interest focuses on understanding mechanisms of molecular pathogenicity relating to periodontal disease. The current work involves the study of virulence factors of major etiological agents of periodontal disease, i.e., Tannerella forsythia (formerly Bacteroides forsythus) and Porphyromonas gingivalis. The ultimate goal of current studies is to better understand the role of T. forsythia and P. gingivalis virulence factors in pathogenesis of periodontal disease. To achieve this goal, proteomic, genomic and immunological approaches are implemented to identify unknown virulence factors of T. forsythia and P. gingivalis, focusing on identification of proteins that are expressed during in vivo, not in vitro, growth. In addition, we investigate antibiotic resistance of oral biofilms. Adopting a novel metagenomic approach, both known and unknown resistance determinants (genes) will be identified and characterized from oral bacteria including those that can not be cultivated in vitro. The results obtained from this study may contribute to the development of new antibiotic drugs specifically designed to inhibit novel resistance mechanisms. A global view of the genetic diversity of antimicrobial resistance among different oral biofilms may lead to a better understanding of the interactions within the oral bacterial community that may lead to oral health or disease.

Selected Publications

1. Lee, S.-W., Sabet M., Um, H.-S., Yang, J, and Kim H. C. Identification and characterization of the genes encoding a unique surface (S-) layer of Tannerella forsythia. Gene 371:102-111, 2006.

2. Sabet, M., Lee, S.-W., Nauman, R. K., Sims, T., and Um, H.-S. The surface (S-) layer is a virulence factor of Bacteroides forsythus. Microbiology, 149: 3617-3627, 2003.

3. Wu, Y., Lee, S.-W., Hillman, J.D., and Progulske-Fox, A. Identification and testing of Porphyromonas gingivalis virulence genes with a pPGIVET System. Infection and Immunity 70:928-37, 2002.

Current Projects

1. Proteomic identification of virulence factors of Tannerella forsythia

Proteomics approaches, including 2-D gel electrophoresis and 2-D immunoblotting analysis, are utilized to identify unknown virulence factors of T. forsythia that are expressed during only in vivo, not in vitro growth. Differentially expressed proteins of T. forsythia will thus be identified and further characterized using genomics tools and data base analysis of the Tannerella forsythia genome. Eventually, specific functions of the identified virulence factors will be assessed by constructing isogenic mutants lacking these proteins in animal studies.

2. Characterization of a surface (S-) layer of Tannerella forsythia

It was found that Tannerella forsythia possesses a unique outer surface component termed surface (S-) layer. Functional studies revealed that the S-layer is involved in pathogenesis through direct interactions with host, resulting hemagglutination, adherence/invasion, and abscess formation in animal model. To further characterize the structure and role(s) of this component in the infectious process, the gene(s) encoding this layer have been identified, cloned and sequenced. It was found that the S-layer actually consist of two large glycoproteins with 200 and 210-kD in molecular size. Construction of single and double isogenic mutants lacking the glycoprotein(s) is now underway.

3.Interaction between P. gingivalis and T. forsythia

It has been observed that P. gingivalis is frequently isolated together with T. forsythia from the periodontal lesion and that a mixed infection of P. gingivalis and T. forsythia significantly enhanced the virulence potential in abscess formation in the animal model. These findings suggest a synergistic effect of two microorganisms in periodontal pathogenesis. In our preliminary study, the coaggregation activity between P. gingivalis 381 and T. forsythia 43037 was observed. The purpose of this current study is to identify surface proteins from P. gingivalis and T. forsythia that are involved in this interaction using biotin labeling and mass spectrometry.

4. Antibiotic resistance determinants of oral bacteria

The purpose of this study is to characterize antibiotic resistance determinants from oral biofilms. Adopting a novel metagenomic approach, both known and unknown resistance determinants (genes) will be identified and characterized from oral bacteria including those that can not be cultivated in vitro. The results obtained from this study may contribute to the development of new antibiotic drugs specifically designed to inhibit novel resistance mechanisms. In addition, a global view of the genetic diversity of antimicrobial resistance among different oral biofilms may lead to a better understanding of the interactions within the oral bacterial community that may lead to oral health or disease.

top