Ocular Surface Microbiome, Virome, and Pathogens in Ophthalmic Disease and Health

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PROJECT SUMMARY/ABSTRACT This K08 application for Thuy Doan, M.D., Ph.D., describes a five year strategy designed to enhance her research and professional skills with the career goal of becoming an independent clinician scientist advancing the understanding of ocular infectious and inflammatory diseases and improving their treatment. Infectious uveitis and ocular infections are a major cause of ocular morbidity and blindness worldwide. While timely and accurate diagnosis is crucial for improved visual outcomes, a definitive diagnosis is often not possible given the significant knowledge gap in factors predisposing to eye infections and the limitations of available diagnostic tests in ophthalmology. The core hypothesis of this proposal is that the bacterial and viral constituents of the ocular surface are involved in ocular health and disease. The goal of this project is to understand this potential pathogen reservoir, the ocular surface microbiome and virome, and to identify infectious agents involved in ocular infections. We propose to advance the capabilities of ocular molecular diagnostics and enhance the understanding of the pathogenesis of ocular infections with the following aims. The first aim will evaluate the use of a next-generation sequencing (NGS)-based approach as a viable clinical diagnostic test for ocular infections. These experiments will directly compare NGS to the current conventional molecular diagnostics using archived intraocular samples. Prospectively collected aqueous samples will then be assessed for potential pathogens. The second aim will characterize the effects of antibiotics on the bacterial and viral communities using samples collected in a large randomized controlled trial. These studies have the potential to improve the diagnostic paradigm and guide targeted interventions for ocular infections. I am committed to developing a clinical research-oriented career in the field of ophthalmology at a major academic institution and understand the need to pursue additional formal training and mentorship. Key components of the career development plan include: (1) laboratory investigations of the ocular surface microbiome, virome, and causes of ocular infectious diseases; (2) mentorship from a multidisciplinary group of scientists and clinician scientists with expertise in advanced molecular techniques, biostatistics, and clinical trial designs; (3) formal didactics to expand molecular biology, biostatistics, and clinical microbiology knowledge; (4) data collection for R01 application; and (5) planned transition to independence including professional development. A scientific advisory and mentorship committee has been assembled to assure progression toward independence. The career development plan will be carried out at the University of California, San Francisco, which provides an exceptional environment to conduct this research, including state- of-the-art facilities and a world-class and supportive community of scientists all critical to my future success.