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Faculty and Staff

Nutritional and Metabolic Biology Doctoral Training Faculty

Stephen H. Tsang, M.D, Ph.D

Laslo A. Bito Associate Professor of Ophthalmology
Professor of Pathology & Cell Biology

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Edward S. Harkness Eye Institute
635 West 165th Street, Floor: 5
New York, NY 10032
Phone:  (212) 305-9535
Appointment:  (212) 305-9535
Fax: (212) 342-5293

 

Degrees

Ph.D. 1996, Columbia University

M.D. 1988, Columbia University

 

Research Interests

Retinal degenerative diseases, including retinitis pigmentosa (RP) and non-exudative (“dry”) age-related macular degeneration (referred to here as simply “AMD”), affect more than 9 million Americans; this number is expected to more than double by 2020. These are devastating diseases that inevitably leave patients with significant and irreversible vision loss. Retinal degenerative diseases represent the best model for studying and developing therapies for neurodegeneration because the retina is highly and uniquely accessible to invasive and noninvasive manipulations and imaging; noninvasive imaging, in particular, is critical for phenotyping/diagnostics and monitoring disease progression (e.g., assessing therapeutic efficacy).


While light-adapted normal rods have a highly anabolic and anaerobic (high lactate) metabolism similar to the Warburg effect observed in stem cells, dark-adapted rods have aerobic (low lactate), high-ATP metabolism similar to neuronal cells. To translate this dark-adaptation therapy to humans (who would rightly reject being maintained in darkness), the PI is  developing  “genetic sunglasses” to promote a constant dark-adapted metabolic state in rods while maintaining a normal light-dark circadian environment.


Studies in the PI’s laboratory are tackling the problem of photoreceptor neuronal 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.  Since 1992, the PI has been culturing embryonic stem cells and has used them to create the first gene-targeted model for a recessive form of RP.  In addition, he has rescued vision in mouse models of RP using gene therapy and stem cells. For cell therapy, the PI’s laboratory was the first to restore retinal function in mice using human induced pluripotent stem (iPS) cells – and to do so without inducing tumor formation. These achievements depended on novel preclinical models generated in the PI laboratory, including gene-targeted humanized mice and human iPS-derived cells – both with patient-specific mutations. PI’s team group also developed the first patient-specific model for an age-related macular degeneration.


Apart from the laboratory’s overall goal, pushing forward the frontiers of regenerative medicine, another major mission is to help students to develop their full potential and become outstanding scientists. In the past, Dr. Tsang’s laboratory has tailored projects to build on and expand students’ and fellows’ existing research skills.

 

Recent Publications - Pubmed

Jin Yang, Yao Li, Lawrence Chan, Yi-Ting Tsai, Wen-Hsuan Wu, Huy V. Nguyen, Chun-Wei Hsu, Xiaorong Li, Lewis M. Brown, Dieter Egli, Janet R. Sparrow, Stephen H. Tsang. Validation of GWAS Alleles with Patient-specific Stem Cell Lines. Hum Mol Genet. 2014, doi: 10.1093/hmg/ddu053.

Wert, K.J., Sancho-Pelluz, and Tsang, S.H. (2014). Mid-stage intervention achieves similar efficacy as conventional early-stage treatment using gene therapy in a pre-clinical model of retinitis pigmentosa Hum Mol Genet. 2014 In Press PMID: 24101599*

Davis RJ, Hsu CW, Tsai YT, Wert KJ, Sancho-Pelluz J, Lin CS, Tsang, SH. (2013). Therapeutic Margins in   a Novel Preclinical Model of Retinitis Pigmentosa. J Neurosci. , Aug 14;33(33):13475-13483.

Li, Y., Tsai, Y.T., Hsu, C.W., Erol, D., Yang, J., Wu, W.H., Davis, R.J., Egli, D., and Tsang, S.H. (2012). Long-term safety and efficacy of human induced pluripotent stem cell (iPS) grafts in a preclinical model of retinitis pigmentosa. Mol Med. 2012 Aug 9. doi: 10.2119.

Wert, K.J., Sancho-Pelluz, J., Davis, R.J., Nishina, P.M., and Tsang, S.H. (2012). Gene Therapy Provides Long-term Visual Function in a Pre-clinical Model of Retinitis Pigmentosa. Hum Mol Genet. 2013 Feb 1;22(3):558-67

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Contact Us

630 West 168th Street, PH1512
Columbia University Medical Center
New York, NY 10032
(212) 305-4808
nutrition@cumc.columbia.edu