MD, PhD, University of Michigan - Ann Arbor
Associate Professor, Ophthalmology and Visual Sciences
RRF Emmett A. Humble Distinguished Director McPherson Eye Research Institute
Sandra Lemke Trout Chair in Eye Research
Inherited and acquired degenerative diseases of the retina are a significant cause of incurable vision loss worldwide. Closer to home, I see the impact of these diseases on afflicted individuals and their families in my pediatric ophthalmology practice at the University of Wisconsin. As such, my laboratory at the Waisman Center utilizes stem cell technology to 1) investigate the cellular and molecular events that occur during human retinal differentiation and 2) generate cells for use in human retinal disease modeling and cell-based rescue or replacement strategies. To meet these goals, we utilize a variety of human cell types, including ES and iPS cells, which have the capacity to mimic retinal development and disease, as well as to delineate the genetic "checkpoints" necessary to produce particular retinal cell types. By understanding the behavior of these cell types in vitro and in vivo, we hope to optimize strategies to delay or reverse the effects of blinding disorders such as retinitis pigmentosa and age–related macular degeneration.
Capowski EE, Wright LS, Phillips MJ, Wallace K, Petelinsek A, Hagstrom A, Pinilla I, Borys K, Lien J, Min JH, Keles S, Thomson JA, Gamm DM, Liang K. (2016) Regulation of WNT Signaling by VSX2 During Optic Vesicle Patterning in Human Induced Pluripotent Stem Cells. Stem Cells. In Press.
Leach LL, Croze RH, Hu Q, Nadar VP, Clevenger TN, Pennington BO, Gamm DM, Clegg DO. (2016) Induced Pluripotent Stem Cell-Derived Retinal Pigmented Epithelium: A Comparative Study Between Cell Lines and Differentiation Methods. Journal of Ocular Pharmacology and Therapeutics. 32(5):317-30. doi: 10.1089/jop.2016.0022.
Wright LS, Pinilla I, Saha J, Clermont JM, Lien JS, Borys KD, Capowski EE, Phillips MJ, Gamm DM. (2015) VSX2 and ASCL1 Are Indicators of Neurogenic Competence in Human Retinal Progenitor Cultures. PLoS One. 20;10(8):e0135830. doi: 10.1371/journal.pone.0135830.
Singh R, Kuai D, Guziewicz KE, Meyer J, Wilson M, Lu J, Smith M, Clark E, Verhoeven A, Aguirre GD, Gamm DM. (2015) Pharmacological Modulation of Photoreceptor Outer Segment Degradation in a Human iPS Cell Model of Inherited Macular Degeneration. Molecular Therapy - Nature. 23(11):1700-11. doi: 10.1038/mt.2015.141.
Ohlemacher SK, Iglesias CL, Sridhar A, Gamm DM, Meyer JS. (2015) Generation of highly enriched populations of optic vesicle-like retinal cells from human pluripotent stem cells. Current Protocols in Stem Cell Biology. 2;32:1H.8.1-1H.8.20. doi: 10.1002/9780470151808.sc01h08s32.
Thompson DA, Ali RR, Banin E, Branham KE, Flannery JG, Gamm DM, Hauswirth WW, Heckenlively JR, Iannaccone A, Jayasundera KT, Khan NW, Molday RS, Pennesi ME, Reh TA, Weleber RG, Zacks DN; Monaciano Consortium. (2015) Advancing therapeutic strategies for inherited retinal degeneration: recommendations from the Monaciano Symposium. Investigative Ophthalmology & Visual Science. Invest Ophthalmol Vis Sci. 2015 Feb 9;56(2):918-31. doi: 10.1167/iovs.14-16049.
Capowski EE, Simonett JM, Clark EM, Wright LS, Howden SE, Wallace KA, Petelinsek AM, Pinilla I, Phillips MJ, Meyer JS, Schneider BL, Thomson JA, Gamm DM. (2014) Loss of MITF expression during human embryonic stem cell differentiation disrupts retinal pigment epithelium development and optic vesicle cell proliferation. Human Molecular Genetics. 23(23):6332-44.
Zhong X, Gutierrez C, Xue T, Hampton C, Vergara MN, Cao LH, Peters A, Park TS, Zambidis ET, Meyer JS, Gamm DM, Yau KW, Canto-Soler MV. (2014) Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs. Nature Communications. 10;5:4047.
Wright LS, Phillips MJ, Pinilla I, Hei D, Gamm DM. (2014) Induced pluripotent stem cells as custom therapeutics for retinal repair: Progress and rationale. Experimental Eye Research. 123:161-72.
Phillips MJ, Perez ET, Martin JM, Reshel ST, Wallace KA, Capowski EE, Singh R, Wright LS, Clark EM, Barney PM, Stewart R, Dickerson SJ, Miller MJ, Percin EF, Thomson JA, Gamm DM. (2014) Modeling human retinal development with patient-specific iPS cells reveals multiple roles for VSX2. Stem Cells. 32(6):1480-92.
Gamm DM, Phillips MJ, Singh R. (2013) Modeling retinal degenerative diseases with human iPS-derived cells: current status and future implications. Expert Review of Ophthalmology. 8(3):213-216.
Singh R, Shen W, Kuai D, Martin JM, Guo X, Smith MA, Perez ET, Phillips MJ, Simonett JM, Wallace KA, Verhoeven AD, Capowski EE, Zhang X, Yin Y, Halbach PJ, Fishman GA, Wright LS, Pattnaik BR, Gamm DM. (2013) iPS cell modeling of Best disease: insights into the pathophysiology of an inherited macular degeneration. Human Molecular Genetics. 22(3):593-607.
Gamm DM, Wright LS. (2013) From embryonic stem cells to mature photoreceptors. Nature Biotechnology. 31(8):712-3.
Phillips MJ, Wallace KA, Dickerson SJ, Miller MJ, Verhoeven A, Martin JM, Wright L, Shen W, Capowski EE, Percin EF, Perez ET, Zhong X, Canto-Soler MV, Gamm DM. (2012) Blood-derived Human iPS Cells Generate Optic Vesicle-like Structures with the Capacity to Form Retinal Laminae and Develop Synapses. Investigative Ophthalmology & Visual Science. 53(4):2007-19.
Howden SE, Gore A, Li Z, Fung HL, Nisler BS, Nie J, Chen G, McIntosh BE, Gulbranson DR, Diol NR, Taapken SM, Vereide DT, Montgomery KD, Zhang K, Gamm DM, Thomson JA. (2011) Genetic correction and analysis of induced pluripotent stem cells from a patient with gyrate atrophy. Proceedings of the National Academy of Sciences USA. 108(16):6537-42.
Meyer JS, Howden SE, Wallace KA, Verhoeven AD, Wright LS, Capowski EE, Pinilla I, Martin JM, Tian S, Stewart R, Pattnaik B, Thomson JA, Gamm DM. (2011) Optic vesicle-like structures derived from human pluripotent stem cells facilitate a customized approach to retinal disease treatment. Stem Cells. 29(8):1206-18.
Lu B, Wang S, Francis PJ, Li T, Gamm DM, Capowski EE, Lund RD. (2010) Cell transplantation to arrest early changes in an ush2a animal model. Investigative Ophthalmology & Visual Science. 51(4):2269-76.
Gamm DM, Meyer JS. (2010) Directed differentiation of human induced pluripotent stem cells: a retina perspective. Regenerative Medicine. May;5(3):315-7.