The goal of this project is to continue my development as an independent scientist and teacher. To achieve this goal, a five-year postdoctoral training program is proposed that will supplement my experience in clinical corneal research, with advanced training in the basic science disciplines of ocular surface biochemistry, molecular biology, microbiology, and bacterial pathogenesis. The program will include courses, seminars and laboratory experience at the Universities of California, San Francisco (UCSF) and Berkeley (UCB). Both UCSF and UCB document incredibly strong research programs in molecular and cell biology, biochemistry, and chemistry, and several key faculty will serve as sponsors. The proposed research project has been carefully designed to complement and enhance those skills obtained during the development period and will provide me with the necessary expertise to analyze the pathogenesis of various ocular surface diseases. Ocular mucins have been shown to protect against corneal infection by inhibiting Pseudomonas aeruginosa adherence to the ocular surface. The purpose of this project is to test the hypothesis that contact lens wear alters the quantity or composition of ocular mucins and thereby interferes with bacterial binding to tear film glycoproteins. The initial phase of this project will investigate the effects of hydrogel contact lens wear on the quantity and composition of secreted ocular mucins. Mucin samples will be obtained by irrigating the human ocular surface, and the optimal technique for purifying mucous glycoproteins will be determined. The quantity of secreted mucin and mucin RNA levels will be compared in contact lens wearers versus controls, and the composition of ocular mucin will be assessed using lectins and specific exoglycosidases. The second phase of experiments will examine the nature of the interaction between P. aeruginosa and ocular mucins, using competitive inhibition studies, and will determine whether or not contact lens wear affects this interaction. The risk of sight-threatening corneal ulceration resulting from overuse of hydrogel lenses is a significant public health concern, and this project will analyze whether or not changes to ocular mucin contribute to this risk. Understanding the effects of contact lens wear on ocular mucin may aid in the design of strategies to prevent or lessen the risk of ulcerative keratitis. This program and research experience will integrate my clinical and basic science training and enable me to formulate hypotheses about clinically observed phenomenon based upon a firm understanding of fundamental ocular biology.
| McNamara, Nancy; Gallup, Marianne; Sucher, Anatol et al. (2006) AsialoGM1 and TLR5 cooperate in flagellin-induced nucleotide signaling to activate Erk1/2. Am J Respir Cell Mol Biol 34:653-60 |
| McNamara, Nancy A; Andika, Renisa; Kwong, Mary et al. (2005) Interaction of Pseudomonas aeruginosa with human tear fluid components. Curr Eye Res 30:517-25 |
| McNamara, Nancy; Gallup, Marianne; Khong, Amy et al. (2004) Adenosine up-regulation of the mucin gene, MUC2, in asthma. FASEB J 18:1770-2 |
| McNamara, Nancy A (2003) Innate defense of the ocular surface. Eye Contact Lens 29:S10-3; discussion S26-9, S192-4 |
| McNamara, Nancy; Basbaum, Carol (2002) Mechanism by which bacterial flagellin stimulates host mucin production. Adv Exp Med Biol 506:269-73 |
| McNamara, N; Khong, A; McKemy, D et al. (2001) ATP transduces signals from ASGM1, a glycolipid that functions as a bacterial receptor. Proc Natl Acad Sci U S A 98:9086-91 |
