learn about THE GAMM LAB

Appointments and Honors

Retina Research Foundation Emmett A. Humble Distinguished Directorship, McPherson Eye Research Institute
Sandra Lemke Trout Chair in Eye Research, McPherson Eye Research Institute
American Institute for Medical and Biological Engineering Fellow

Subspecialty

Pediatric ophthalmology and adult strabismus

Medical and Surgical Interests

• Double vision
• Eyelid abnormalities
• Genetic disorders
• Pediatric and adult strabismus management and surgery
• Pediatric ophthalmology
• Tear duct surgery

Research Interests

• Diseases of the retina, stem cell biology
• Human pluripotent stem cells
• Disease modeling
• Regenerative medicine
• Retinitis pigmentosa
• Age-related macular degeneration
• Retinal, photoreceptor, and RPE cell development
• Retinal stem cell biology/human pluripotent stem cell biology
• Retinal developmental biology
• Inherited and acquired retinal degenerations
• Cell and gene therapies for retinal degenerations
• Stem cell-based retinal disease modeling

Inherited and acquired eye diseases that culminate in the degeneration of photoreceptors and retinal pigment epithelium (RPE) are a significant cause of visual morbidity. The expansion and targeted differentiation of human stem and progenitor cells in vitro provide an essential source of biological material for modeling retinal development and potential cell-based treatments for these debilitating diseases. The aims of our laboratory are to 1) investigate cellular and molecular events that occur during retinogenesis and 2) provide cells for use in rescue or replacement therapies for retinal degenerative diseases.

To meet these goals, we utilize a variety of cell types. Retinal and neural progenitors are amenable to viral transformation and demonstrate the capacity to efficiently deliver neuroprotective factors directly to the retina. Human embryonic stem cells (hESCs) are used to delineate the genetic checkpoints necessary to produce a particular retinal cell type and serve as a model system for studying human retinal development. Lastly, we have developed a protocol to direct induced pluripotent stem cells (iPS) towards a retinal lineage in a manner similar to hESCs, which has allowed us to create cell-based models of human retinal degenerative diseases and begin transplantation experiments. 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 inherited and acquired eye diseases such as retinitis pigmentosa and macular degeneration.

Research Highlights

Dr. Gamm is a world-class researcher in cell-based therapies for retina diseases. His work in the field spans decades and has contributed to countless citations. He was one of the first to use human pluripotent stem cell technology to derive retinal cells and tissues, and the first to patent human retinal organoid technology, which led to the establishment of Opsis Therapeutics, a Madison-based retinal cell therapeutic company. Dr. Gamm’s lab has pioneered many aspects of stem cell-based retinal disease modeling and cell therapeutic development. He has contributed to the adaptation of human embryonic stem (hES) and human induced pluripotent stem cells (hiPS) cell technology for use in patients with retinal degenerative conditions. The lab’s focus is on applications of hESC and hiPSC technology to replace photoreceptors and/or retinal pigment epithelium (RPE) loss during the course of retinal degenerative disease or injury. The lab has adapted a 3D hPSC retinal organoid culture method to facilitate production of these cells under cGMP and highly scalable conditions and has developed robust hPSC photoreceptor reporter lines to track cells in vitro and in vivo. In addition, the Gamm lab has developed biodegradable microscaffolds to deliver photoreceptors ± RPE to the subretinal space in a controlled, organized manner. Overall, Dr. Gamm is extensively involved with the National Eye Institute, industry, and foundations exploring the potential of hESC and hiPSC technology to benefit patients with blinding disorders stemming from outer retinal disease. These interactions contributed to the National Eye Institute’s 2013 decision to pursue photoreceptor regeneration as part of their Audacious Goals Initiative.
Imaging transplanted photoreceptors in living nonhuman primates with single cell resolution
3D microstructured scaffolds to support photoreceptor polarization and maturation

A significant highlight of Dr. Gamm’s career is the culture and differentiation of 3D neural retina (NR) organoids derived from hESCs and hiPSCs. Dr. Gamm developed a way to investigate human retinal development and disease in a manner not previously possible. Following the initial development of hESC (and later hiPSC) technology, the challenge was to design methods to target differentiation of these versatile cells along specific lineages. Their background in human retinal development allowed them to take on this challenge and examine 3D methods of propagating neural retinal progenitor cells (NRPCs) and RPE from human tissue. The lab then applied this knowledge to create a protocol to produce 3D NR organoids. These organoids, which form laminated retinal tissues, contain a nearly pure population of multipotent NPRCs that differentiate into all major classes of retinal neurons (and Müller glia) in a sequence and time frame approximating human retinogenesis. Using this system, Dr. Gamm has examined the authenticity of hESC- and hiPSC-derived retinal tissues and progeny – including photoreceptors – and have probed mechanisms underlying their genesis in culture.
Reproducibility and staging of 3D human retinal organoids across multiple pluripotent stem cell lines

Another arm of Dr. Gamm’s research explores the utilization of hESCs and hiPSCs to model retinal disease and test therapeutics. Using the hESC- and hiPSC-based 3D retinal differentiation system, he is able to generate large, essentially pure cultures of RPE and NR, the latter of which contains a high percentage of photoreceptor precursors that mature over time to form rods and cones bearing inner and light-sensitive outer segments. This has been harnessed in Dr. Gamm’s lab to create, characterize, and test the first in vitro models of multiple retinal disorders, including Best vitelliform macular dystrophy, gyrate atrophy, and an inherited defect in retinal development caused by mutations in the Visual Systems Homeobox 2 (VSX2) gene, among others.
Human iPSC modeling elucidates mutation-specific responses to gene therapy in a genotypically diverse dominant maculopathy

Dr. Gamm knows the importance of training and knowledge sharing globally, so he continues to host and mentor visiting international graduate students, visiting professors and or lab members from many countries to support global vision research advancements.

• In 2007, Dr. Gamm mentored visiting graduate student, Matthias Reike from the University of Technology, Darmstadt, Germany. Project entitled “Culture of retinal and cortical neurospheres.”
• In 2007, Dr. Gamm mentored visiting graduate student, Julian Esteve, from the University of Alicante, Spain. Project entitled, “Overexpression of CHX10 and NEUROD in human cortical and retinal progenitor cells.”
• In 2009, Dr. Gamm sponsored, Ilaria Bellantuono, MD, PhD of the University of Sheffield, United Kingdom, for a one-month research fellowship, who was the recipient of the 2009 UK-US Stem Cell Collaboration Development Award; Project: Deriving mesenchymal cell types from human ES and iPS cells.
• In 2014, Dr. Gamm collaborated with Jane Sowden’s Laboratory of London, United Kingdom, Institute of Child Health, University College London to support a one-month research fellow, Jorn Lakowski, Ph.D.
• In 2020, Dr. Gamm partnered with Sorbonne University, Physiology, Physiopathology and Therapeutics in Paris, France to serve on the thesis committee of graduate student Juliette Wohlschlegel.

Education

Fellowship: Pediatric Ophthalmology, University of Wisconsin Hospital and Clinics, Madison, WI

Residency: University of Wisconsin Hospital and Clinics, Madison, WI

Internship: Spectrum Hospital, Grand Rapids, MI

Medical School: University of Michigan Medical School, Ann Arbor, MI

Additional Studies: University of Michigan School of Graduate Studies, Ann Arbor, MI