faculty

Gwynneth Offner Associate Professor

education

Ph.D, Boston Universit

research goals

Research in our laboratory is focused on understanding the relationship between the structural properties and functional roles of a group of glycoproteins known as mucins. Mucins are expressed by epithelial cells lining the digestive, respiratory and reproductive tracts and serve to protect epithelial surfaces from mechanical, bacterial and chemical injury. To date, several distinct human mucin genes (MUC1-MUC12) have been identified. While these genes are expressed in tissue-specific patterns, the corresponding protein products share several common structural features. Mucins contain greater than 50% carbohydrate by weight, primarily in the form of O-linked glycans attached to serine and threonine residues found in clustered repetitive sequences in the central portion of the molecule. Alterations in the patterns of mucin gene expression have been found in a number of human diseases including inflammatory bowel disease and cancer.

Recently, it has been determined that mucins can be divided into two groups: secreted mucins and membrane-associated mucins. Secreted mucins, also called gel-forming mucins, form large oligomers and function primarily in epithelial protection. Membrane-associated mucins are monomeric and are anchored to the cell surface by a hydrophobic membrane-spanning domain. The functions of these mucins remain unclear. Salivary glands synthesize and secrete high molecular weight oligomeric mucins into the oral cavity where they facilitate speech and swallowing and lubricate and protect soft tissue surfaces. We have recently shown that mucins are also expressed on oral epithelial cells and that these include the membrane-associated mucins MUC1 and MUC4. Our hypothesis is that these mucins, which are rigid molecules extending up to 2 microns from the cell surface function in epithelial defense by modulating the binding of oral microbes to the cell surface. Furthermore, MUC1 contains consensus tyrosine phosphorylation sites in its cytoplasmic tail and we are investigating whether binding of oral pathogens to this mucin initiates a signal transduction cascade which may be critical in the host response to infection.

recent publications

Gipson, I.K., Moccia, R., Spurr-Michaud, S., Argueso, P., Gargiulo, A.R., Hill, J.A., Offner, G.D. and Keutmann, H.T. The amount of MUC5B in cervical mucus peaks at midcycle. J. Clin. Endocrin. and Metabol. 86:594-600, 2001.

Offner, G.D. and Troxler, R.F. Heterogeneity of High-molecular weight salivary mucins. Adv. Dent Res. 14:69-75, 2000.

Rayment, S.A., Liu, B., Offner, G.D., Oppenheim, F.G. and Troxler, R.F. Immunoquantification of human salivary mucins MG1 and MG2 in stimulated whole saliva: factors influencing mucin levels. J. Dent. Res. 79:1765-1772, 2000.

Nunes, D.P., Afdhal, N.H. and Offner, G.D. A recombinant bovine gallbladder mucin domain binds biliary lipids and accelerates cholesterol crystal nucleation. Gastroenterology 116:936-942, 1999.

Offner, G.D., Nunes, D.P., Keates, A.C., Afdhal, N.H. and Troxler, R.F. The amino-terminal sequence of MUC5B contains conserved multifunctional D domains: Implications for tissue-specific mucin function. Biochem. Biophys.Res. Commun, 1998.

Keates, A.C., Nunes, D.P., Afdhal, N.H. and Offner, G.D. Molecular cloning of a major human gallbladder mucin. Complete C-terminal sequence and genomic organization of MUC5B. Biochem. J. 324:295-303, 1997.

recent grants

Mucin and Non-mucin Proteins in Gallstone Pathogenesis, NIDDK- R01 (4/97 to 3/02)

Structure and Function of Human Salivary Mucins, NIDCR-R01 (8/99 to 7/04)

Membrane-bound Mucins in Salivary Glands and Saliva, NIDCR- R01; pending)