Current Research and Scholarly Interests
Our focus is the development of personalized medicine for eye diseases through translation of our discoveries in proteomics, genomics, and phenomics in humans, mice and tissue culture models.
My laboratory team is composed of scientists, surgeons, engineers, and students who are dedicated to curing blindness. We use high-throughput technologies (proteomics, genomics, phenomics) to identify candidate disease molecules. These are validated using biochemistry, tissue culture, and animal models. The findings are then directly translated into personalized medical therapies in humans. Major projects include: 1. Proteomics of vitreoretinal disease. 2. Protein biomarkers and therapeutcs for uveal melanoma. 3. Drug development for inflammation. 4. Gene therapy for eye disease.
We identified CAPN5 as the first gene to cause uveitis. The gene encodes the calcium-activated cysteine protease. We are investigating the structure-function effects of mutations on its crystal structure and enzymatic activity, structure, function within photoreceptor cells, and activation of intracellular signaling pathways. We also conduct clinical and human genetic studies into the etiology and therapy of autoimmune eye disease.
Our unique access to human surgical eye fluid and tissues allowed us to map the human proteome in normal and diseased eyes with vitreoretinal conditions. We have identified major enzymatic pathways associated with diseases such as age-related macular degeneration, diabetic retinopathy, and autoimmunity. Specific molecules have been validated in mice and in cultured cells.
In partnership with the Sanger Institute, we are conducting a high-throughput phenotype screen in genetically modified mice. We have identified numerous genes that cause eye diseases in mice and their human correlates. The strategic integration of this genotype-phenotype platform provides excellent projects for mechanistic investigations.
Using mouse models of eye disease and human stem cells, we are creating new drugs to treat treat blinding conditions like AMD, diabetic retinopathy, and retinitis pigmentosa.
The laboratory allows highly motivated individuals to be creative in an immersive, interactive environment intensely focused on the restoration of sight. Please contact us to learn more.
