Stephen Tsang

Studies in Dr. Tsang's laboratory are tackling the problem of photoreceptor cell degeneration by pursuing investigations in three areas, two of which include mouse models: probing the role of phosphodiesterase (PDE) signaling in retinal degeneration, developing stem cell-based therapies for retinal degeneration, and correlating the genotypes of various human photoreceptor cell degenerations with the phenotypes revealed in fundus autofluorescence (AF) images.

Dr. Tsang is a recognized expert in gene-targeting and gene-editing in stem cells. Most recently, he has been invited to lecture at the gene-editing workshop during the annual Association for Research in Vision & Ophthalmology (ARVO) 2015 & 2016 Annual Meetings; and as a Moderator for Gene Editing/Rewriting the Genome: Moving from Association to Biology and Therapeutics session during the 65^thAmerican Society of Human Genetics (ASHG) Annual Meeting, and lecturer at 2015 CRISPR Revolution meeting at Cold Spring Harbor.

Since 1992 Dr. Tsang has been culturing embryonic stem (ES) cells and in 1995 created the first mouse model for a recessive form of retinitis pigmentosa (RP) by applying homologous recombination to ES cell technology. Three elements define the strength and uniqueness of his laboratory. First, by leveraging his genetics clinical practice in which over 1000 retinal patients are cared for, Dr. Tsang brings an array of valuable clinical resources to his research, including tissue, stem cells, live imaging data, and genotyping data.

Second, Dr. Tsang and his students are recognized authorities in a broad array of state-of the-art technologies: gene-editing, transgenesis, viral vectors, stem-cell engineering, proteomics, pre-implantation embryo injection, retinal surgery, electrophysiology, and non-invasive imaging in mice and humans. Dr. Tsang has expertise in designing and testing gene therapy strategies in pre-clinical models, developing patient-specific knock-in models, generating of patient cell lines and providing care to patients with a personalized medicine approach.

Third, Dr. Tsang is one of a handful of clinicians who can direct the full spectrum of bench-to-bedside research. His research on cGMP-phosphodiesterase (PDE6) is a case in point. PDE6 defects lead to blindness in 72,000 people worldwide. He generated the world’s first gene-targeted model of retinitis pigmentosa (a PDE6 mutant), and then used these mice to dissect the underlying pathophysiology. These studies led to novel and fundamental discoveries on PDE6 regulation of G-protein-coupled-receptor signaling and, eventually, preclinical testing in the same mice; of the different therapies tested, viral-gene therapy is slated for clinical trials.

Few have the clinical and scientific credentials, innovation, and ability to apply genome engineering to understanding the pathogenesis of retinal dysfunction that Dr. Tsang and his facility do. His electrophysiology service evaluates and cares for patients with the most complicated hereditary and inflammatory retinal diseases in the New York area and beyond. Recently, he edited a book on the uses of gene targeting in stem cells, Stem Cell Biology and Regenerative Medicine in Ophthalmology, Springer Press, NY, 2012.