Justine Smith

MD, University of Adelaide (Australia), 1989
PhD, Flinders University of South Australia, 1998
Associate Professor of Ophthalmology and Cell & Developmental Biology
Thelma & Gilbert Schnitzer Professor of Ophthalmic Research

The focus of my laboratory is the vascular endothelium. In particular we study the different endothelia that exist within the eye and the role these cells play in human diseases that lead to blindness. Today it is recognized that the molecular phenotype and function of vascular endothelial cell subpopulations vary considerably across the different tissues of the body. This concept is referred to as vascular endothelial heterogeneity. Such diversity may be exploited therapeutically because different endothelial cell-specific proteins or activities may present targets for tissue-specific treatment of diseases that preferentially involve one tissue or organ. Different endothelial cell subpopulations of the eye are key layers in several of the leading causes of blindness in the US, i.e., diabetic retinopathy, age-related macular degeneration and posterior uveitis. In diabetic retinopathy, retinal EC dysfunction & pathological new vessel growth correlate with accumulation of advanced glycation end-products. An imbalance of angiogenic and anti-angiogenic factors promotes proliferation of choroidal endothelial cells in the neovascular networks that characterize age-related macular degeneration. In posterior uveitis, leukocytes and microbes must cross blood-retinal barrier - of which the retinal endothelial cell is a key component - to access the eye and initiate inflammation or infection, respectively. Our research concerns the unique phenotypes of the retinal and the choroidal vascular endothelial cells. We have developed techniques for isolation of human donor-matched ocular endothelial cells, a unique resource for such work. We use diverse molecular methods, including state-of-the-art microarray & proteomic profiling techniques, as well as more routine assays such as real-time RT-PCR, Western blot and ELISA. We test candidate molecules in functional assays relevant to disease pathology, e.g, capillary tubes formation assays to test the role of potential angiogenic regulators, and binding and migration assays to study homing interactions between the ocular endothelial cells and leukocyte subsets or microbes. Our work is very translational, since we aim to improve the treatment of blinding diseases, and human pathological specimens are often studied in parallel with the basic laboratory experiments.

Kleinman ME, Yamada K, Takeda A, et al. Sequence- and target-independent suppression of angiogenesis by siRNA via TLR3. Nature 2008; 452: 591-597

Smith JR, Choi D, Chipps TJ, et al. Microarray identifies unique gene expression profiles of human retinal and choroidal vascular endothelium in donor-matched cell cultures. Invest Ophthalmol Vis Sci 2007; 48: 2676-2684.

Chipps TJ, Streeter PR, Franc DT, et al. Modification of the Woodruff-Stamper assay demonstrates binding of Toxoplasma gondii tachyzoites to retinal vascular endothelium. J Immunol Methods 2006; 312: 209-213.

To contact Dr. Smith directly: smithjus@ohsu.edu