Diabetic retinopathy is among the most common complications of diabetes. Basement membrane thickening and pericyte loss are early changes associated with the development of diabetic retinopathy. I speculate that these events disrupt Notch signaling, which depends upon juxtaposition of cellular membranes, and also impair cell signaling cross-talk between Notch and TGF-? signaling. To test this hypothesis, I propose to: (i) establish a cell culture system to measure cell-cell interactions mediated by Notch using imaging methods;(ii) examine how Notch/TGF-? signaling is affected in vascular cells cultured under conditions resembling a diabetic environment;and, (iii) use mouse models and postmortem human eye tissue for examining the role of Notch/TGF- ? interactions in diabetic retinopathy. I propose a training plan that will enable me to accomplish the proposed experiments and a strategy for transition towards career independence.
In this research proposal I propose to test the hypothesis that a signaling pathway termed Notch plays a role in the development of diabetic retinopathy, which is a prevalent cause of vision loss. I propose a training plan that will allow me to study this problem using cell culture systems and in vivo models of diabetes.
|Ung, Cindy; Sanchez, Angie V; Shen, Lishuang et al. (2017) Whole exome sequencing identification of novel candidate genes in patients with proliferative diabetic retinopathy. Vision Res 139:168-176|
|Amarnani, Dhanesh; Machuca-Parra, Arturo Israel; Wong, Lindsay L et al. (2017) Effect of Methotrexate on an In Vitro Patient-Derived Model of Proliferative Vitreoretinopathy. Invest Ophthalmol Vis Sci 58:3940-3949|
|Machuca-Parra, Arturo I; Bigger-Allen, Alexander A; Sanchez, Angie V et al. (2017) Therapeutic antibody targeting of Notch3 signaling prevents mural cell loss in CADASIL. J Exp Med 214:2271-2282|
|Lam, Jonathan D; Oh, Daniel J; Wong, Lindsay L et al. (2017) Identification of RUNX1 as a Mediator of Aberrant Retinal Angiogenesis. Diabetes 66:1950-1956|
|Sánchez-Palencia, Diana M; Bigger-Allen, Alex; Saint-Geniez, Magali et al. (2016) Coculture Assays for Endothelial Cells-Mural Cells Interactions. Methods Mol Biol 1464:35-47|
|Primo, Vincent; Graham, Mark; Bigger-Allen, Alexander A et al. (2016) Blood biomarkers in a mouse model of CADASIL. Brain Res 1644:118-26|
|Arboleda-Velasquez, Joseph F; Valdez, Cammi N; Marko, Christina K et al. (2015) From pathobiology to the targeting of pericytes for the treatment of diabetic retinopathy. Curr Diab Rep 15:573|
|Kim, Leo A; Wong, Lindsay L; Amarnani, Dhanesh S et al. (2015) Characterization of cells from patient-derived fibrovascular membranes in proliferative diabetic retinopathy. Mol Vis 21:673-87|
|Quiroz, Yakeel T; Schultz, Aaron P; Chen, Kewei et al. (2015) Brain Imaging and Blood Biomarker Abnormalities in Children With Autosomal Dominant Alzheimer Disease: A Cross-Sectional Study. JAMA Neurol 72:912-9|
|Arboleda-Velasquez, Joseph F; Primo, Vincent; Graham, Mark et al. (2014) Notch signaling functions in retinal pericyte survival. Invest Ophthalmol Vis Sci 55:5191-9|
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