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 deveop 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.
Th 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.

Public Health Relevance

A better understanding of accessory lacrimal gland (tear producing gland) cell biology and identification of stem cells in these tissues will provide a basi for developing treatments and transplantation efforts for patients with severe dry eye disease and eye surface diseases.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08EY024339-02
Application #
8827355
Study Section
Special Emphasis Panel (ZEY1-VSN (02))
Program Officer
Agarwal, Neeraj
Project Start
2014-04-01
Project End
2019-03-31
Budget Start
2015-04-01
Budget End
2016-03-31
Support Year
2
Fiscal Year
2015
Total Cost
$236,427
Indirect Cost
$17,513
Name
University of Illinois at Chicago
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
Shah, Dhara; Ali, Marwan; Shukla, Deepak et al. (2017) Effects of histatin-1 peptide on human corneal epithelial cells. PLoS One 12:e0178030
Ali, Mohsin H; Azar, Nathalie F; Aakalu, Vinay et al. (2017) Congenital cavitary optic disc anomaly and Axenfeld's anomaly in Wolf-Hirschhorn syndrome: A case report and review of the literature. Ophthalmic Genet :1-4
Aakalu, Vinay Kumar; Parameswaran, Sowmya; Maienschein-Cline, Mark et al. (2017) Human Lacrimal Gland Gene Expression. PLoS One 12:e0169346
Jefferson, Gina D; Aakalu, Vinay K; Braniecki, Marylee (2017) Tumid lupus: An unexpected diagnosis for the otolaryngologist. Am J Otolaryngol 38:257-259
Liu, Catherine Y; Hirayama, Masatoshi; Ali, Marwan et al. (2017) Strategies for Regenerating the Lacrimal Gland. Curr Ophthalmol Rep 5:193-198
Patel, Rakesh M; Aakalu, Vinay K; Setabutr, Pete et al. (2017) Efficacy of Muller's Muscle and Conjunctiva Resection With or Without Tarsectomy for the Treatment of Severe Involutional Blepharoptosis. Ophthal Plast Reconstr Surg 33:273-278
Ali, Marwan; Shah, Dhara; Pasha, Zeeshan et al. (2017) Evaluation of Accessory Lacrimal Gland in Muller's Muscle Conjunctival Resection Specimens for Precursor Cell Markers and Biological Markers of Dry Eye Disease. Curr Eye Res 42:491-497
Mittal, Nupur; Aakalu, Vinay; Mehendele, Sangeeta et al. (2016) Primary Orbital Histiocytic Sarcoma in a Child Successfully Treated With Multiagent Chemotherapy. J Pediatr Hematol Oncol 38:653-657
Jain, Sachin; Patel, Rakesh M; Hage, Ziad et al. (2016) Cerebrospinal Fluid Leak Presenting as Epiphora. Ophthal Plast Reconstr Surg 32:e26-8
Shah, Dhara; Ali, Marwan; Pasha, Zeeshan et al. (2016) Histatin-1 Expression in Human Lacrimal Epithelium. PLoS One 11:e0148018

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