You are here

Stephen Tsang

M.D., Ph.D.
Associate Professor in Opthalmology
Columbia University, College of Physicians and Surgeons
Associate Professor of Pathology-Cell Biology

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 65thAmerican 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. 

Select Publications: 

Bassuk AG, Zheng A, Li Y, Tsang SH, Mahajan VB. Precision Medicine: Genetic Repair of Retinitis Pigmentosa in Patient-Derived Stem CellsScience Reports. 2016 Jan 27; 6:11969.

Yang J, Li Y, Chan L, Tsai YT, Wu WH, Nguyen HV, Hsu CW, Li X, Brown LM, Egli D, Sparrow JR, Tsang SH. Validation of genome-wide association study (GWAS)-identified disease risk alleles with patient-specific stem cell lines. (2014) Human Molecular Genetics. Jan 31. PMID: 24497574.

Li Y, Wu W-H, Hsu C-W, Nguyen H-V, Tsai Y-T, Nagasaki T, Maumenee IH, Yannuzzi LA, Hoang QV, Hua H, Egli D, Tsang SH. Gene therapy in patient-specific stem cell lines and a preclinical model of retinitis pigmentosa with membrane frizzled-related protein (MFRP) defects. (2014) Molecular Therapy. 2014 Sep;22(9):1688-97.

Li Y, Tsai Y-T, Hsu C-W, Erol D, Yang J, Wu W-H, Davis RJ, Egli D, Tsang SH. Long-term safety and efficacy of human induced pluripotent stem cell (iPS) grafts in a preclinical model of retinitis pigmentosa. (2012) Molecular Medicine. 18:1312-9.

Wert KJ, Davis RJ, Sancho-Pelluz J, Nishina PM, Tsang SH. Gene therapy provides long-term visual function in a pre-clinical model of retinitis pigmentosa. (2013) Human Molecular Genetics. 22:558-567.

Davis RJ, Hsu CW, Tsai Y, Wert KJ, Sancho-Pelluz J, Lin CS, Tsang SH. Therapeutic margins in a novel preclinical model of retinitis pigmentosa. (2013) Journal of Neuroscience. 33:13475-83.

Koch SF, Tsai YT, Duong JK, Wu WH, Hsu CW, Wu WP, Bonet-Ponce L, Lin CS, Tsang SH. Halting progressive neurodegeneration in advanced retinitis pigmentosa. (2015) . 2015 Sep 1;125(9):3704-13. doi: 10.1172/JCI82462. Epub 2015 Aug 24.