NON-SJÖGREN'S SYNDROME AND SJÖGREN'S SYNDROME KERATOCONJUNCTIVITIS SICCA: A SPECTRUM OF INFLAMMATORY DRY EYE ABSTRACT This is an application for a mentored K23 career development award to Dr. John A. Gonzales, a uveitis specialist at The F.I. Proctor Foundation at the University of California, San Francisco. Dr. Gonzales is establishing himself as an investigator in patient-oriented research focused on ocular inflammatory conditions including keratoconjunctivitis sicca and uveitis. This K23 Award will provide Dr. Gonzales the support necessary to complete the following goals: (1) to become skilled in epidemiology research by utilizing the Sjögren's International Collaborative Clinical Alliance (SICCA) Registry's wealth of data; (2) to understand the nuances and utility of high throughput sequencing technology to; (3) to learn and utilize advanced statistical and epidemiology methods necessary for success in clinical studies; and (4) to develop the skills needed to transition to an independent investigator. To achieve these goals Dr. Gonzales has assembled a team of mentors comprised of the following experts: • Dr. Tom Lietman, a Professor in both the Departments of Ophthalmology and Epidemiology and Biostatistics at UCSF. Dr. Lietman has been awarded NIH-funded grants for seminal randomized clinical trials in infectious and inflammatory ocular diseases including Eliminating trachoma with repeat mass drug treatment, the Steroids for Cornea Ulcers Trial, and the Mycotic Ulcer Treatment Trial. • Dr. Caroline Shiboski, Professor in the Department of Orofacial Sciences is a Sjögren's syndrome expert. She has extensive experience leading the SICCA study eading an international effort to obtain definitive approval from both ACR and the European League Against Rheumatism (EULAR) of a final set of criteria to be used for entry into Sjögren's syndrome clinical trials • Dr. Laura Koth, Associate Professor in the Department of Medicine in the Division of Pulmonary and Critical Care Medicine. Dr. Koth is an expert in genomics and bioinformatics utilizing high-throughput sequencing to characterize autoimmune pulmonary disease. The research proposed herein seeks to accomplish the following: (1) to examine how non-Sjögren's and Sjögren's-related keratoconjunctivitis impact quality of life, depression, and mortality; (2) to identify accompanying features of corneal neuropathology and neuropathic pain when patients convert from non- Sjögren's keratoconjunctivitis to Sjögren's syndrome; and (4) to characterize Sjögren's syndrome on a gene expression level. This research will form the basis for an R01 application before the end of the K award. Dr. Gonzales's passion and motivation for the proposed project, the environment at the Proctor Foundation and at UCSF, and the support of his mentors will set the stage for a rigorous and rewarding career development into an independent researcher.