School of Dental Medicine - University at Buffalo

Sharma, Ashu Ph.D Associate Professor, Department of Oral Biology

Address:

211 Foster Hall

Buffalo, NY 14214

(716)829-2759

sharmaa@buffalo.edu

Research Profile

The human oral cavity is a highly diverse ecosytem containing more than 500 species of bacteria, including both cultivable and non-cultivable species. It is believed that existence of a select few Gram-negative anaerobes, known as the ‘red-complex’, is responsible for periodontitis or gum-associated disease. These bacteria live as biofilms and form bacterial plaque in spaces between gums and teeth. The bacterial products cause inflammation by inducing inflammtory cytokine release from host cells. Therefore, if these bacteria are not erradicated, inflammation continues and leads to destruction of tooth supporting tissue and eventually tooth loss. My lab studies the pathogenic mechanisms of the red-complex bacteria by utilizing molecular-genetic and biochemical approaches; the bacteria of the red-complex include Porphyromonas gingivalis, Tannerella forsythia (formerly Bacteroides forsythus) and Treponema denticola (a spirochete). Our overall objectives are to gain a better understanding of how these pathogenic bacteria initiate colonization, form biofilms and initiate tissue destructive host immune responses critical for disease progression. The research focuses on identifying virulence factors these bacteria produce and host-cell receptors involved in their recognition. Identification of these virulence factors and their receptor should pave the way for developing intervention strategies, such as vaccines, against periodontal bacteria. In this regard, we have developed genetic systems whereby non-pathogenic oral streptococci (Streptococci gordonii) can be engineered to expression vaccine antigens of choice. These genetically modified streptococcal vectors can be utilized for vaccine delivery by oral route.

Current Research Activities:
1. Molecular mechanisms of pathogenesis of T. forsythia: bacterial invasion and epithelial cell response to bacterial challenge.
2. Investigation of mixed bacterial biofilms and investigation of T. forsythia genes regulated in biofilms
3. Functional-genomic approaches to identify novel factors produced by microbiota of the oral cavity.

Representative Publications Search Publications in MEDLINE

Select Publications (2004-2009)

1. Loimaranta, V, Hytönen, J, Pulliainen, A. T, Sharma, A Jorma, J, Strömberg, N, and Finne, J. Leucine rich repeats of bacterial surface proteins serve as common pattern recognition motifs of human scavenger receptor Gp34. J. Biol. Chem, Epub ahead of print May 22, 2009.
2. Honma, K. Mishima, E., Ingaki, S. and Sharma A. The OxyR homologue in Tannarella forsythia regulates expression of oxidative stress responses and biofilm formation. Microbiology. 155:1912-1922 (Epub April 23). 2009.
3. Morozumi, T. Sharma, A and De Nardin E. The function al effects of the -455G/A polymorphism on the IL-6-induced expression of the b-fibrinogen gene may be due to linkage disequilibrium with other functional polymorphisms. Immunological Investigations 38: 1-13. 2009.
4. Onishi S, Honma K, Liang S, Stathopoulou P, Kinane D, Hajishengallis G, and Sharma A. TLR2-mediated interleukin-8 expression in gingival epithelial cells by the Tannerella forsythia leucine-rich repeat BspA protein. Infect Immun. 76:198-205. 2008
5. Honma, K., Inagaki, S., Okuda, K., Kuramitsu, H. k., and Sharma A. Role of a Tannerella forsythia Exopolysaccharide Synthesis Operon in Biofilm Development. Microbial Pathogenesis. 42:156-166. 2007.
6. Sahingur, S. E., Boehm, T. K., Sojat, H. T., and De Nardin, E. Fibrinogen-neutrophil interactions in response to fMLP and Porphyromonas gingivalis fimbrial peptides. Immunol. Invest. 35:63-74. 2006.
7. Chen W, Honma K, Sharma A, Kuramitsu H. K. A universal stress protein of Porphyromonas gingivalis is involved in stress responses and biofilm formation. FEMS Microbiol Lett. 264:15-21. 2006
8. Inagaki, S., Onishi, S., Kuramitsu, H. K. and Sharma, A. Porphyromonas gingivalis Vesicles Enhance Attachment and the Leucine-Rich Repeat BspA Protein is Required for Invasion of Epithelial Cells by Tannerella forsythia. Infect. Immun. 74: 5023-5028. 2006
9. Inagaki S, Kuramitsu H. K, and Sharma A. Contact dependent regulation of a Tannerella forsythia virulence factor, BspA, in biofilms. FEMS Microbiology Letters. 249:291-296. 2005
10. Sharma, A*, Inagaki, S., Honma, K., Sfintescu, C, Baker, P., and Evans, RT. Alveolar Bone Loss in Mice Involves Leucine-Rich Repeat BspA Protein, Journal of Dental Research 84:462-467. 2005
11. Sharma, A*., Inagaki, S., Sigurdson, W, and Kuramitsu, H. K. Synergy between Tannerella forsythia and Fusobacterium nucleatum in biofilm formation. Oral Microbiology immunology 20-39-42. 2005
12. Ikegami, A. Honma, K., Sharma, A, and Kuramitsu, H. K. Multiple functions of the leucine-rich repeat protein (LrrA) of Treponema denticola. Infect. Immun 72:4619-4627. 2004
13. Sojar, H. T., Sharma, A, and Genco, R.J. Porphyromonas gingivalis fimbriae binds to neoglycoproproteins: evidence for a lectin-like interaction. Biochimie. 86: 245-249. 2004
14. Ruddy M. J, Shen F, Smith J. B, Sharma A, Gaffen S. L.Interleukin-17 regulates expression of the CXC chemokine LIX/CXCL5 in osteoblasts: implications for inflammation and neutrophil recruitment. J Leukoc Biol. 6:135-144. 2004 Apr 23 2004 [Epub ahead of print]