David Gamm, MD, PhD

Position title: Sandra Lemke Trout Chair in Eye Research, Professor, Ophthalmology and Visual Sciences

MD, PhD, University of Michigan – Ann Arbor
Professor, Ophthalmology and Visual Sciences
RRF Emmett A. Humble Distinguished Director McPherson Eye Research Institute
Sandra Lemke Trout Chair in Eye Research

Contact Information

Waisman Center
1500 Highland Avenue
Room T609
Madison, WI 53705
608-261-1516
dgamm@wisc.edu
Lab Website: Gamm Lab, Stem Cell Research Program

Research Statement

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.

Selected Publications

Lee, I. K., Xie, R., Luz-Madrigal, A., Min, S., Zhu, J., Jin, J., Edwards, K. L., Phillips, M. J., Ludwig, A. L., Gamm, D. M., Gong, S., & Ma, Z. (2023). Micromolded honeycomb scaffold design to support the generation of a bilayered RPE and photoreceptor cell construct. Bioactive materials, 30, 142–153. https://doi.org/10.1016/j.bioactmat.2023.07.019
Ludwig, A. L., Mayerl, S. J., Gao, Y., Banghart, M., Bacig, C., Fernandez Zepeda, M. A., Zhao, X., & Gamm, D. M. (2023). Re-formation of synaptic connectivity in dissociated human stem cell-derived retinal organoid cultures. Proceedings of the National Academy of Sciences of the United States of America, 120(2), e2213418120. https://doi.org/10.1073/pnas.2213418120
Mayerl, S. J., Bajgai, S., Ludwig, A. L., Jager, L. D., Williams, B. N., Bacig, C., Stoddard, C., Sinha, D., Philpot, B. D., & Gamm, D. M. (2022). Human retinal organoids harboring IMPG2 mutations exhibit a photoreceptor outer segment phenotype that models advanced retinitis pigmentosa. Stem cell reports, 17(11), 2409–2420. https://doi.org/10.1016/j.stemcr.2022.09.004
Rempel, S. K., Welch, M. J., Ludwig, A. L., Phillips, M. J., Kancherla, Y., Zack, D. J., Gamm, D. M., & Gómez, T. M. (2022). Human photoreceptors switch from autonomous axon extension to cell-mediated process pulling during synaptic marker redistribution. Cell reports, 39(7), 110827. https://doi.org/10.1016/j.celrep.2022.110827
Samimi, K., Pattnaik, B. R., Capowski, E. E., Saha, K., Gamm, D. M., & Skala, M. C. (2022). In situ autofluorescence lifetime assay of a photoreceptor stimulus response in mouse retina and human retinal organoids. Biomedical Optics Express, 13(6), 3476–3492. https://doi.org/10.1364/BOE.455783
Saha, A., Capowski, E., Fernandez Zepeda, M. A., Nelson, E. C., Gamm, D. M., & Sinha, R. (2022). Cone photoreceptors in human stem cell-derived retinal organoids demonstrate intrinsic light responses that mimic those of primate fovea. Cell stem cell, 29(3), 460–471.e3. https://doi.org/10.1016/j.stem.2022.01.002
Wahlin, K. J., Cheng, J., Jurlina, S. L., Jones, M. K., Dash, N. R., Ogata, A., Kibria, N., Ray, S., Eldred, K. C., Kim, C., Heng, J. S., Phillips, J., Johnston, R. J., Jr, Gamm, D. M., Berlinicke, C., & Zack, D. J. (2021). CRISPR Generated SIX6 and POU4F2 Reporters Allow Identification of Brain and Optic Transcriptional Differences in Human PSC-Derived Organoids. Frontiers in cell and developmental biology, 9, 764725. https://doi.org/10.3389/fcell.2021.764725
Lee, I. K., Ludwig, A. L., Phillips, M. J., Lee, J., Xie, R., Sajdak, B. S., Jager, L. D., Gong, S., Gamm, D. M., & Ma, Z. (2021). Ultrathin micromolded 3D scaffolds for high-density photoreceptor layer reconstruction. Science advances, 7(17), eabf0344. https://doi.org/10.1126/sciadv.abf0344
Tao, Y., Cao, J., Li, M., Hoffmann, B., Xu, K., Chen, J., Lu, X., Guo, F., Li, X., Phillips, M. J., Gamm, D. M., Chen, H., & Zhang, S. C. (2020). PAX6D instructs neural retinal specification from human embryonic stem cell-derived neuroectoderm. EMBO reports, 21(9), e50000. https://doi.org/10.15252/embr.202050000
van Landingham, S. W., Puccetti, D., Potter, H., Gamm, D., Diamond, E. L., & Lucarelli, M. J. (2020). Necrotizing myositis in a rectus muscle arising in the setting of long-standing Langerhans cell histiocystosis and recent dabrafenib treatment. American journal of ophthalmology case reports, 20, 100868. https://doi.org/10.1016/j.ajoc.2020.100868
Aboualizadeh, E., Phillips, M. J., McGregor, J. E., DiLoreto, D. A., Jr, Strazzeri, J. M., Dhakal, K. R., Bateman, B., Jager, L. D., Nilles, K. L., Stuedemann, S. A., Ludwig, A. L., Hunter, J. J., Merigan, W. H., Gamm, D. M., & Williams, D. R. (2020). Imaging Transplanted Photoreceptors in Living Nonhuman Primates with Single-Cell Resolution. Stem cell reports, 15(2), 482–497. https://doi.org/10.1016/j.stemcr.2020.06.019
Sinha, D., Steyer, B., Shahi, P. K., Mueller, K. P., Valiauga, R., Edwards, K. L., Bacig, C., Steltzer, S. S., Srinivasan, S., Abdeen, A., Cory, E., Periyasamy, V., Siahpirani, A. F., Stone, E. M., Tucker, B. A., Roy, S., Pattnaik, B. R., Saha, K., & Gamm, D. M. (2020). Human iPSC Modeling Reveals Mutation-Specific Responses to Gene Therapy in a Genotypically Diverse Dominant Maculopathy. American journal of human genetics, 107(2), 278–292. https://doi.org/10.1016/j.ajhg.2020.06.011
Udry F, Decembrini S, Gamm DM, Déglon N, Kostic C, Arsenijevic Y. (2020). Lentiviral mediated RPE65 gene transfer in healthy hiPSCs-derived retinal pigment epithelial cells markedly increased RPE65 mRNA, but modestly protein level. Science Reports, 10(1):8890. doi: 10.1038/s41598-020-65657-y. PMID: 32483256; PMCID: PMC7264209.
Bronstein R, Capowski EE, Mehrotra S, Jansen AD, Navarro-Gomez D, Maher M, Place E, Sangermano R, Bujakowska KM, Gamm DM, Pierce EA. (2020). A combined RNA-seq and whole genome sequencing approach for identification of non-coding pathogenic variants in single families. Human Molecular Genetics, 29(6):967-979. doi: 10.1093/hmg/ddaa016. PMID: 32011687; PMCID: PMC7158377.
Shahi PK, Hermans D, Sinha D, Brar S, Moulton H, Stulo S, Borys KD, Capowski E, Pillers DM, Gamm DM, Pattnaik BR. (2019). Gene Augmentation and Readthrough Rescue Channelopathy in an iPSC-RPE Model of Congenital Blindness. American Journal of Human Genetics, 104(2):310-318. doi: 10.1016/j.ajhg.2018.12.019.
Capowski EE, Samimi K, Mayerl SJ, Phillips MJ, Pinilla I, Howden SE, Saha J, Jansen AD, Edwards KL, Jager LD, Barlow K, Valiauga R, Erlichman Z, Hagstrom A, Sinha D, Sluch VM, Chamling X, Zack DJ, Skala MC, Gamm DM. (2019). Reproducibility and staging of 3D human retinal organoids across multiple pluripotent stem cell lines. Development, 146(1). pii: dev171686. doi: 10.1242/dev.171686.
Jung YH, Phillips MJ, Lee J, Xie R, Ludwig AL, Chen G, Zheng Q, Kim TJ, Zhang H, Barney P, Min J, Barlow K, Gong S, Gamm DM, Ma Z. (2018). 3D Microstructured Scaffolds to Support Photoreceptor Polarization and Maturation. Advanced Materials, 30(39):e1803550. doi: 10.1002/adma.201803550.
Galloway CA, Dalvi S, Shadforth AMA, Suzuki S, Wilson M, Kuai D, Hashim A, MacDonald LA, Gamm DM, Harkin DG, Singh R. (2018). Characterization of Human iPSC-RPE on a Prosthetic Bruch’s Membrane Manufactured From Silk Fibroin. Investigative Ophthalmology & Visual Science, 1;59(7):2792-2800.
Lakowski J, Welby E, Budinger D, Di Marco F, Di Foggia V, Bainbridge JWB, Wallace K, Gamm DM, Ali RR, Sowden JC. (2018). Isolation of Human Photoreceptor Precursors via a Cell Surface Marker Panel from Stem Cell-Derived Retinal Organoids and Fetal Retinae. Stem Cells, 36(5):709-722. doi: 10.1002/stem.2775.
Langer KB, Ohlemacher SK, Phillips MJ, Fligor CM, Jiang P, Gamm DM, Meyer JS. (2018). Retinal Ganglion Cell Diversity and Subtype Specification from Human Pluripotent Stem Cells. Stem Cell Reports, 10(4):1282-1293. doi: 10.1016/j.stemcr.2018.02.010.
Phillips MJ, Jiang P, Howden S, Barney P, Min J, York NW, Chu LF, Capowski EE, Cash A, Jain S, Barlow K, Tabassum T, Stewart R, Pattnaik BR, Thomson JA, Gamm DM. (2018). A Novel Approach to Single Cell RNA-Sequence Analysis Facilitates In Silico Gene Reporting of Human Pluripotent Stem Cell-Derived Retinal Cell Types. Stem Cells. 36(3):313-324. doi: 10.1002/stem.2755.
Phillips MJ, Capowski EE, Petersen A, Jansen AD, Barlow K, Edwards KL, Gamm DM. (2018). Generation of a rod-specific NRL reporter line in human pluripotent stem cells. Scientific Reports, 8(1):2370. doi: 10.1038/s41598-018-20813-3.
Steyer B, Bu Q, Cory E, Jiang K, Duong S, Sinha D, Steltzer S, Gamm D, Chang Q, Saha K. (2018). Scarless Genome Editing of Human Pluripotent Stem Cells via Transient Puromycin Selection. Stem Cell Reports, 13;10(2):642-654. doi: 10.1016/j.stemcr.2017.12.004.
Galloway CA, Dalvi S, Hung SSC, MacDonald LA, Latchney LR, Wong RCB, Guymer RH, Mackey DA, Williams DS, Chung MM, Gamm DM, Pébay A, Hewitt AW, Singh R. (2017). Drusen in patient-derived hiPSC-RPE models of macular dystrophies. Proceedings of the National Academy of Sciences of the United States, 26;114(39):E8214-E8223. doi: 10.1073/pnas.1710430114.
Guziewicz KE, Sinha D, Gómez NM, Zorych K, Dutrow EV, Dhingra A, Mullins RF, Stone EM, Gamm DM, Boesze-Battaglia K, Aguirre GD. (2017). Bestrophinopathy: An RPE-photoreceptor interface disease. Progress in Retinal and Eye Research, 58:70-88. doi: 10.1016/j.preteyeres.2017.01.005.
Lavine JA, Farnoodian M, Wang S, Darjatmoko SR, Wright LS, Gamm DM, Ip MS, Sorenson CM, Sheibani N. (2017). β2-Adrenergic Receptor Antagonism Attenuates CNV Through Inhibition of VEGF and IL-6 Expression. Investigative Ophthalmology and Visual Science, 58(1):299-308. doi: 10.1167/iovs.16-20204.
George A, Zand DJ, Hufnagel RB, Sharma R, Sergeev YV, Legare JM, Rice GM, Scott Schwoerer JA, Rius M, Tetri L, Gamm DM, Bharti K, Brooks BP. (2016) Biallelic Mutations in MITF Cause Coloboma, Osteopetrosis, Microphthalmia, Macrocephaly, Albinism, and Deafness. American Journal of Human Genetics. 1;99(6):1388-1394. doi: 10.1016/j.ajhg.2016.11.004.
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, 34(11):2625-2634. doi: 10.1002/stem.2414.
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.