Dr. Tsang successfully treated preclinical models of Pde6a, Pde6b, Mfrp, Rho, Cngb1 and autosomal recessive bestrophin retinopathies. He has expertise in designing and testing genome engineering strategies in pre-clinical models, developing patient-specific knock-in models, generating of patient cell lines and providing care to patients with a precision medicine approach. PI is also leading efforts in FDA trials for retinal degenerations, including PDE6A, RAB geranylgeranyl transferase, RPGR, CNGB3, CNGA3 and ABCA4 retinopathies. Since 1992, PI has been culturing embryonic stem (ES) cells, and, in 1995, created the first mouse model for a recessive form of Retinitis Pigmentosa.
K08EY000408 and MSTP # T32 GM 073667 had allowed the PI to become one of a handful of clinicians to direct the full spectrum of bench-to-bedside research. PI’s research on cGMP-phosphodiesterase (PDE6) is a case in point. PDE6 defects lead to blindness in 72,000 people worldwide. PI 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.
PI has extensive experience in creating patient-specific induced pluripotent stem cell (iPSC) and related iPS-RPE cell lines as disease models for retinal diseases. PI created patient-specific iPSC and iPSC-RPE lines and used them as a disease model in the preclinical study of gene therapy for Membrane Frizzled-related Protein (MFRP), an autosomal recessive retinitis pigmentosa (RP). (Li Y, ……, TSANG, S.H. 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).