School of Dental Medicine - University at Buffalo

Bobek, Libuse M.A., Ph.D. Professor, Department of Oral Biology

Address:

109 Foster Hall

Buffalo, NY 14214

(716)829-2465

lbobek@buffalo.edu

Research Profile

1. Antimicrobial activity/mechanism of action of salivary proteins/peptides
2. Regulation of salivary gland-specific gene expression

Many proteins and glycoproteins found in human saliva have protective functions critical for oral health. Our research concentrates on the following two areas of salivary research:
1. Structure-function relationship of MUC7 mucin (modulator of microbial interactions and clearance from the oral cavityand) and mechanism of antimicrobial action of MUC7-derived peptides. We have discovered that a low molecular weight salivary mucin (MUC7)-derived peptides exhibit potent and a broad-spectrum antimicrobial activities in vitro. This includes antifungal activity against clinical important fungal strains (such as Candida albicans and Cryptococcus neoformans, and their azole-resistant and amphotericin B-resistant counterparts) and antibacterial activity (including Streptococcus mutans, bacteria causing tooth caries). The observed potencies of these peptides are comparable to that of the currently used antimicrobial agents. Due to undesirable toxicity and the rapid development of drug-resistant strains to conventional antimicrobials, increased interest has been developed in the discovery and use of naturally occurring (non-toxic) antimicrobial peptides. The long-range goal of our research is to develop the novel salivary-derived peptides into effective antimicrobial therapeutic agents (particularly for drug-resistant infections (primarily in immunocompromised patients, e.g. AIDS and organ transplant patients). These peptides could also be used as antibacterial and antifungal components of artificial saliva for the treatment of salivary dysfunctions, clinically manifested by increase in plaque formation, caries and periodontitis.

2. To determine the mechanisms that control the regulation of salivary gland-specific gene expression. In particular, we are interested in the regulation of expression of the low molecular weigh human salivary mucin gene, MUC7 (including developmental role(s) of MUC7 gene, physiological and pathophysiological regulators; signal transduction pathways). Examination of the human MUC7 expression in vivo by transgenic mice technology showed that one transgenic mice line expresses MUC7 at high level and in the same tissue and cell specific manner as humans. We will use these mice for studies directed towards understanding the intracellular signaling and gene regulation mechanisms mediating mucin overproduction in response to clinically important insults (such as air pollution, gram-positive and gram-negative bacteria, and tobacco smoke). We are also utilizing normal human tracheo-bronchial epithelial cells to investigate the MUC7 expression under normal and pathological conditions in vitro, and we plan to develop salivary cell lines for these studies. Lastly, we plan to determine any qualitative and quantitative differences in the MUC7 transcripts and/or glycoprotein in normal human salivary glands versus benign and malignant salivary tumors (alterations in expression maybe exploited for cancer diagnostic and prognostic assessments).

Representative Publications Search Publications in MEDLINE

Lis M, Fuss JR, Bobek LA. Exploring the Mode of Action of Antimicrobial Peptide MUC7 12-mer by Fitness Profiling of Saccharomyces cerevisiae Genome-Wide Mutant Collection. Antimicrob Agents Chemother. 2009 Jul 13. [Epub ahead of print]

Lis M, Bobek LA. Proteomic and metabolic characterization of a Candida albicans mutant resistant to the antimicrobial peptide MUC7 12-mer. FEMS Immunol Med Microbiol. 2008 Oct;54(1):80-91. Epub 2008 Aug 1.

Intini G, Andreana S, Buhite RJ, Bobek LA A comparative analysis of bone formation induced by human demineralized freeze-dried bone and enamel matrix derivative in rat calvaria critical-size bone defects. J Periodontol. 2008; Jul;79(7):1217-24.

Wei GX, Campagna AN, Bobek LA. Factors affecting antimicrobial activity of MUC7 12-mer, a human salivary mucin-derived peptide. Ann Clin Microbiol Antimicrob. 2007 Nov 11;6:14.

Intini G, Andreana S, Intini FE, Buhite RJ, Bobek LA. Calcium sulfate and platelet-rich plasma make a novel osteoinductive biomaterial for bone regeneration. J Transl Med. 2007 Mar 7;5:13.

Li S, Bobek LA. Functional Analysis of human MUC7 mucin gene 5'-flanking region in lung epithelial cells. Am J Respir Cell Mol Biol. 2006 Nov;35(5):593-601. Epub 2006 Jun 15.

Wei GX, Campagna AN, Bobek LA. Effect of MUC7 peptides on the growth of bacteria and on Streptococcus mutans biofilm. J Antimicrob Chemother. 2006 Jun;57(6):1100-9. Epub 2006 Apr 4.

Li S, Intini G, Bobek LA. Modulation of MUC7 Mucin by Exogenous Factors in Airway Epithelial Cells in vitro and in vivo. Am J Respir Cell Mol Biol. 2006 Jul;35(1):95-102. Epub 2006 Mar 2.

Muralidharan R, Bobek LA. (2005). Antifungal activity of human salivary mucin-derived peptide, MUC7 12-mer, in a murine model of oral candidiasis. J Pept Res. 2005 Dec;66 Suppl 1:82-9.

Wei GX, Bobek LA. Human salivary mucin MUC7 12-mer-L and 12-mer-D peptides: antifungal activity in saliva, enhancement of activity with protease inhibitor cocktail or EDTA, and cytotoxicity to human cells. Antimicrob Agents Chemother. 2005 Jun;49(6):2336-42.