Study of Accessory Lacrimal Gland and Precursor Cell Biology

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Project Abstract This is a proposal for a K08 Mentored Clinical Scientist Career Development Award to train Dr. Vinay Kumar Aakalu. The primary goal of this application is to serve as a basis for training Dr. Aakalu in the critical skills necessary to develop into an independent scientific investigator focused on lacrimal cell and precursor cell biology. The specific aims of the proposed educational program are the performance of 1) graduate level cell, molecular, stem cell biology and basic translational/clinical trial course work at the University of Illinois at Chicago 2) basic scientific investigations in accessory lacrimal cell and stem cell biology under the guidance of an experienced four person mentoring committee 3) seminar and conference participation at the University of Illinois and outside the University of Illinois. The mentoring committee is made up of experts in stem cell, ocular, molecular cell biology and translational research. Each mentor is well experienced in training clinician- scientists. The mentoring committee will be focused on guiding Dr. Aakalu in the development of research skills, analytical thinking and the ethical performance of basic and translational research. The overarching research goals of the proposal are to develop a better understanding of accessory lacrimal cell biology and to identify and isolate precursor cells from this tissue. The specific aims of the project are to: 1. Develop a better understanding of ALG distribution, growth requirements, and changes with patient characteristics. 1a. A three dimensional map of the cadaveric human orbit will be constructed to determine the location of ALG tissue throughout the ocular surface as a basis for rational harvesting decisions. 1b. Characterize ALG tissue in human surgical specimens and relate the robustness or histopathologic changes in these tissues to relevant patient characteristics (age, gender, race, hormonal status). 1c. Develop ALG cultures from human surgical specimens to better understand requirements for cell survival and expansion. 2. Establish the presence of precursor cells in ALG tissue and isolate and characterize these precursor cells. 2a. Identify precursor marker positive ALG cells and determine a signature marker pattern using human specimens and immunohistochemistry on tissue microarrays. 2b. Isolate precursor candidate cells utilizing fluorescence cell sorting and determine if changes in precursor candidate cell populations are noted with different patient characteristics. 2c. Determine if precursor candidate cells isolated have stem cell properties. 2d. Establish cultures from precursor candidates and determine if these cultures can produce functional ALG cells.