Peter M.J. Quinn

Peter M.J. Quinn
Columbia University | CU · Department of Ophthalmology

PhD

About

61
Publications
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Introduction
I am a Principal Investigator and Associate Research Scientist in the Department of Ophthalmology at CUIMC. My focus is to provide clinically translatable impact using iPSC-derived retinal organoid-based approaches for the understanding and treatment of retinal degenerative diseases. I am developing gene augmentation and prime editing therapeutics for the amelioration of the phenotypic, histopathological, and molecular changes in inherited retinal disease iPSC-derived retinal organoid models.

Publications

Publications (61)
Article
Full-text available
The mammalian apical-basal determinant Crumbs homolog-1 (CRB1) plays a crucial role in retinal structure and function by the maintenance of adherens junctions between photoreceptors and Müller glial cells. Patients with mutations in the CRB1 gene develop retinal dystrophies, including early-onset retinitis pigmentosa and Leber congenital amaurosis....
Article
Full-text available
Variations in the human Crumbs homolog-1 (CRB1) gene lead to an array of retinal dystrophies including early-onset of retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) in children. To investigate the physiological roles of CRB1 and CRB2 in retinal Müller glial cells, we analysed mouse retinas lacking both proteins in Müller glial cells...
Article
Full-text available
Human retinal organoids from induced pluripotent stem cells (hiPSCs) can be used to confirm the localization of proteins in retinal cell types and to test transduction and expression patterns of gene therapy vectors. Here, we compared the onset of CRB protein expression in human fetal retina with human iPSC-derived retinal organoids. We show that C...
Article
Full-text available
Recent advances have driven the development of stem cell-derived, self-organizing, three-dimensional miniature organs, termed organoids, which mimic different eye tissues including the retina, cornea, and lens. Organoids and engineered microfluidic organ-on-chips (organ chips) are transformative technologies that show promise in simulating the arch...
Article
Full-text available
The developing vertebrate eye cup is partitioned into the neural retina (NR), the retinal pigmented epithelium (RPE), and the ciliary margin (CM). By single-cell analysis, we showed that fibroblast growth factor (FGF) signaling regulates the CM in its stem cell–like property of self-renewal, differentiation, and survival, which is balanced by an ev...
Article
Full-text available
Neurodegenerative diseases are characterized by the progressive degeneration of the neuronal cells and their networks, hampering the function of the central or peripheral nervous system [...]
Patent
The present disclosure provides vectors comprising a transgene(s) encoding more than one isoform of Crumbs homologue-1 (CRB1) (e.g., CRB1-A and CRB1-B), and compositions thereof, for use in the treatment or prevention of CRB1-related diseases and disorder (e.g., autosomal recessive retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA)).
Poster
Purpose: Mutations in Crumbs homologue 1 (CRB1) gene cause chronic and disabling autosomal recessive retinal dystrophies, including Leber congenital amaurosis 8 (LCA8) and retinitis pigmentosa 12 (RP12). Currently, there are approximately 80,000 CRB1 patients worldwide and there is no available treatment to date. The human retina contains three maj...
Book
This volume details the history of Retinitis Pigmentosa and current treatment options. Chapters guide readers through CRISPR, gene therapy, stem cell therapy, next-generation sequencing methods, gene editing, and translational applications of other therapies to the treatment of Retinitis Pigmentosa. Written in the successful Methods in Molecular Bi...
Article
Full-text available
Autosomal dominant disorders present unique challenges, as therapeutics must often distinguish between healthy and diseased alleles while maintaining high efficiency, specificity, and safety. For this task, CRISPR/Cas remains particularly promising. Various CRISPR/Cas systems, like homology-directed repair, base editors, and prime editors, have bee...
Article
Mutations in Rhodopsin (RHO) are the most common causes of autosomal dominant retinitis pigmentosa (adRP), accounting for 20 to 30% of all cases worldwide. However, the high degree of genetic heterogeneity makes development of effective therapies cumbersome. To provide a universal solution to RHO-related adRP, we devised a CRISPR-based, mutation-in...
Article
Full-text available
Retinal ganglion cell (RGC) degeneration is the most common neurodegenerative disorder that causes irreversible blindness worldwide. It is characterized by visual field defect and progressive optic nerve atrophy. The underlying pathophysiology and mechanisms of this neurodegenerative disorder remain largely unknown. RGCs are a population of central...
Article
Full-text available
Inherited retinal diseases (IRDs) are chronic, hereditary disorders that lead to progressive degeneration of the retina. Disease etiology originates from a genetic mutation—inherited or de novo—with a majority of IRDs resulting from point mutations. Given the plethora of IRDs, to date, mutations that cause these dystrophies have been found in appro...
Preprint
Full-text available
The developing vertebrate eye cup is partitioned into the neural retina (NR), the retinal pigmented epithelium (RPE) and the ciliary margin (CM). By single cell analysis, we showed that a gradient of FGF signaling regulates demarcation and subdivision of the CM and controls its stem cell-like property of self-renewal, differentiation and survival....
Article
Full-text available
Achromatopsia is characterized by amblyopia, photophobia, nystagmus, and color blindness. Previous animal models of achromatopsia have shown promising results using gene augmentation to restore cone function. However, the optimal therapeutic window to elicit recovery re-mains unknown. Here, we attempted two rounds of gene augmentation to generate r...
Article
Full-text available
Early in vivo embryonic retinal development is a well-documented and evolutionary conserved process. The specification towards eye development is temporally controlled by consecutive activation or inhibition of multiple key signaling pathways, such as the Wnt and hedgehog signaling pathways. Recently, with the use of retinal organoids, researchers...
Article
Advances in tissue mimetics are paving the way for interrogating both the pathobiology of human disease and innovative therapeutic paradigms. In this issue of Cell Stem Cell, Manian et al., 2021 develop a novel iPSC-derived retinal pigment epithelium (RPE)-choriocapillaris (CC) complex that recapitulates key features of macular degenerations.
Conference Paper
Purpose:The proper development of cone and rod photoreceptors (PRs) requires the timed activation of different genetic programs. Alterations in these specific programs trigger developmental defects of cell fate specification, that are likely to yield visual impairments. Methods:Previous reports show that ONECUT1 (OC1) is involved in the repression...
Article
Macular degeneration (MD) is characterized by the progressive deterioration of the macula and represents one of the most prevalent causes of blindness worldwide. Abnormal intracellular accumulation of lipid droplets and pericellular deposits of lipid-rich material in the retinal pigment epithelium (RPE) called drusen are clinical hallmarks of diffe...
Article
Full-text available
Mutations in the Crumbs homologue 1 (CRB1) gene cause inherited retinal dystrophies such as early-onset retinitis pigmentosa and Leber congenital amaurosis. A Brown Norway rat strain was reported with a spontaneous insertion-deletion (indel) mutation in exon 6 of Crb1. It has been reported that these Crb1 mutant rats show vascular abnormalities ass...
Article
Full-text available
Mutations in the PTEN-induced kinase 1 (PINK1) and Parkin RBR E3 ubiquitin-protein ligase (PARKIN) genes are associated with familial forms of Parkinson's disease (PD). PINK1, a protein kinase, and PARKIN, an E3 ubiquitin ligase, control the specific elimination of dysfunctional or superfluous mitochondria, thus fine-tuning mitochondrial network an...
Article
Retinitis pigmentosa (RP), the most common form of rod-cone dystrophy, is caused by greater than 3100 mutations in more than 71 genes, many of which are preferentially expressed in rod photoreceptors. Cone death generally follows rod loss regardless of the underlying pathogenic mutation. Preventing the secondary loss of cone photoreceptors would pr...
Article
Full-text available
The Crumbs complex has prominent roles in the control of apical cell polarity, in the coupling of cell density sensing to downstream cell signaling pathways, and in regulating junctional structures and cell adhesion. The Crumbs complex acts as a conductor orchestrating multiple downstream signaling pathways in epithelial and neuronal tissue develop...
Thesis
Full-text available
By investigating the roles of CRB proteins in mouse, non-human-primate, human fetal retina, and iPSC-derived retinal organoids, this thesis describes important insights to pathobiology in CRB1-retinitis pigmentosa (RP) and CRB1-Leber congenital amaurosis (LCA) disease models. The thesis describes AAV gene and cell therapy-based tools as therapeutic...
Article
Full-text available
Tissue-specific progenitor cells form a potential population for cell-based transplantation therapy. Müller glial cells are suggested to contain, or represent, the progenitor pool in the retina and can dedifferentiate and regenerate neuronal cells in fish and amphibians. However, the Müller glial cells of mammals have a more limited regenerative ca...
Chapter
In vitro retinal organoid modeling from human pluripotent stem cells is becoming more common place in many ophthalmic laboratories worldwide. These organoids mimic human retinogenesis through formation of organized layered retinal structures that display markers for typical retinal cell types. Pivotally these humanized retinal models provide a step...
Article
Full-text available
Müller glial cells are large neuroglial cells that extend throughout the entire retina, they function to maintain homeostasis and retinal integrity. In teleost fish, in response to retinal damage, Müller cells can re-enter the cell cycle, dedifferentiate and regenerate neuronal cells. Therefore, increasing our knowledge about these cells might open...
Poster
Well established 3D in vitro models are necessary for complementing research on retina physiology and degeneration, allowing the investigation of the molecular networks governing human pathophysiological scenarios. A retinal organoid culture system from human induced pluripotent stem cells (hiPSC) has been established to explore early development,...
Poster
Purpose Many retinal diseases results in the loss of inner/outer segments (IS/OS) of photoreceptors (PRCs). PRCs can be infected with some recombinant adeno-associated virus (AAV) serotypes for gene augmentation therapy, CRISPR/Cas9 gene editing or CRISPR/Cas13 RNA base editing. AAVs can efficiently deliver up to 4.9 kb ssDNA to the retina/retinal...
Poster
Purpose: Mutations in the Crumbs homologue-1 (CRB1) gene cause early-onset Retinitis pigmentosa (RP) in children. Mice lacking CRB1 show moderate retinal degeneration limited to one quadrant of the retina while in retinas lacking CRB2 the entire retina is affected. In the mouse retina, CRB1 is localized in Müller glial cells (MGCs) and CRB2 in MGCs...
Conference Paper
Purpose: Mutations in the CRB1 gene cause severe inherited retinal dystrophies from birth or early childhood. The early developmental processes of normal and diseased human retinas are still not well understood. Having in vitro human retinas which mimic these developmental processes is highly desirable allowing a bridge in treatment development bet...
Poster
Crumbs proteins (CRB1 and CRB2) localization at the subapical region adjacent to adherens junctions at the outer limiting membrane in the retina, critical to cell adhesion between photoreceptor cells (PRCs) and Müller Cells (MGCs), varies between species. It is unclear which AAV capsid can efficiently infect human MGCs and which AAV gene therapy pr...
Article
Full-text available
Once considered science fiction, gene therapy is rapidly becoming scientific reality, targeting a growing number of the approximately 250 genes linked to hereditary retinal disorders such as retinitis pigmentosa and Leber's congenital amaurosis. Powerful new technologies have emerged, leading to the development of humanized models for testing and s...
Poster
Purpose : Human Crumbs homologue-1 gene mutations lead to severe inherited retinal dystrophies. Mouse Crb1 is localised in only Müller cells and Crb2 in both Müller and photoreceptor cells. Removal of either mouse Crb1 or Crb2 in Müller cells leads to a mild retinal degeneration suggesting overlapping functions for the two proteins. But we have yet...
Poster
Purpose : The Crumbs complex is crucial for cell polarity and epithelial tissue function with Crumbs homologue-1 mutations causing severe inherited retinal dystrophies. Removal of Crb2 from photoreceptors causes retinal degeneration mimicking retinitis pigmentosa (RPE), whereas removal of Crb1 from Müller cells mimics late onset RPE. Here we study...
Conference Paper
ARVO 2015 Annual Meeting, Emerging Trend and Hot Topic Purpose: Mutations in the CRB1 gene lead to severe recessive inherited retinal dystrophies. Gene transfer therapy is the most promising cure for retinal dystrophies and has primarily been applied for recessive null conditions via a viral gene expression vector transferring a cDNA encoding an e...
Article
Full-text available
Mutations in the CRB1 gene lead to severe recessive inherited retinal dystrophies : Gene transfer therapy is the most promising cure for retinal dystrophies and has primarily been applied for recessive null conditions via a viral gene expression vector transferring a cDNA encoding an enzyme or channel protein, and targeting expression to one cell t...
Article
Full-text available
Development in the central nervous system is highly dependent on the regulation of the switch from progenitor cell proliferation to differentiation, but the molecular and cellular events controlling this process remain poorly understood. Here, we report that ablation of Crb1 and Crb2 genes results in severe impairment of retinal function, abnormal...

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Projects

Projects (3)
Project
I am guest-editing a special issue on "Oxidative Stress in Neurodegeneration and Neuroinflammation" in the journal Antioxidants with Drs. Francisco Ambrósio and Peter Quinn. We welcome submissions concerning all research models (e.g., in vitro, iPSC-derived cells, organoids, animal models), focusing on all the different nervous system tissues and cell types (e.g., retina, brain, spinal cord, neurons, microglia, astrocytes) and using all types of molecular and cellular approaches that contribute to unraveling and clarifying the pathophysiology and the molecular mechanisms related to neurodegenerative disorders. https://www.mdpi.com/journal/antioxidants/special_issues/Oxidative_Stress_Neurodegeneration