NNRL members competed in the 26th annual NIH relay

About our work

The primary goal of our research is to develop novel therapies for retinal and macular degeneration by delineating cellular pathways and regulatory networks underlying photoreceptor development, aging, and disease.

In addition to gene therapy, we are developing stem cell-based approaches for drug discovery and photoreceptor replacement. We seek to understand how photoreceptors originate from stem cells and form synaptic circuits to initiate complex visual process, and how their function is compromised during aging and in disease.

We collaborate with scientists all over the world to identify genetic variants/mutations that cause or modify clinical phenotypes in patients with retiitis pigmentosa, cone dystrophies, Leber congenital amaurosis, or age-related macular degeneration.

See our latest news, highlights, and accomplishments here.

Current research

The eye is our window to the world and to the brain. The process of vision begins in the retina, and in humans the retina supplies almost 30% of the sensory input to the brain.

Any damage to retinal neurons can lead to devastating consequences, including loss of vision. Retinal and macular diseases are a major cause of visual impairment and affect the quality of life of millions worldwide.

The basic premise guiding research of the Retinal Development, Genetics & Therapy section is that clinical manifestations of disease result from perturbations in normal cellular behavior and adaptive changes to genetic variants/mutations interacting with environmental factors. With a focus on the retina, our laboratory wishes to advance our understanding of several fundamentally important and interrelated biological processes and help pursue clinical interventions that exploit these advances.

In particular, we seek to understand:

  • How neurons differentiate from neuroepithelial progenitors (or stem cells);
  • How these neurons form functional synaptic circuits;
  • How neuronal function is accomplished in the normal retina and how it is compromised during aging and in disease conditions; and
  • How we can repair the damage or treat the degenerative disease.

The following themes encompass the many projects that we are developing in our lab:

Regulatory networks guiding retinal development, homeostasis and aging

One of our major efforts is to elucidate gene regulatory networks that guide differentiation of photoreceptor subtypes from retinal progenitor cells in vitro in the mouse retina and in vitro using human and mouse-derived embryonic (ESCs) and induced pluripotent stem cells (iPSCs). We are also focusing on the identification of molecules that control the specificity of photoreceptor synapse formation. Our work extends to the study of gene networks underlying photoreceptor homeostasis and aging. We apply cutting-edge genomic technologies (e.g., Next Generation Sequencing) to perform whole genome expression profiles, transcription factor binding and epigenetic studies.

Genetic basis of human retinal disease

The genetic component of our laboratory is dedicated to the identification of genetic defects in inherited retinal degenerative diseases and genetic susceptibility variants associated with common multifactorial diseases (age-related macular degeneration, AMD, and diabetic retinopathy). We combine whole exome sequencing, targeted chip genotyping and well-established computational workflows for new disease gene discovery. We pursue the study of candidate genes to delineate molecular pathways leading to retinal pathology, focusing on retinal/macular degenerative diseases and on AMD. We take advantage of an extended colony of mouse models of retinal disease, zebrafish mutants, and we develop in vitro disease models using patient-derived iPSCs.

Treatment paradigms for retinal diseases

The ultimate goal of our laboratory is to develop treatment paradigms for retinal and macular degenerative diseases (specifically those caused by mutations in CEP290, RPGR and RP2), using a comprehensive set of approaches including pluripotent stem cells (ESCs and iPSCs), small molecules against specific gene or pathway-based targets, and gene replacement using viral vectors.

Jobs, fellowships, and internships

Several positions are available to study genetic and epigenetic control of neuronal differentiation, synaptogenesis and energy homeostasis in the retina, functional genomics, and stem cell-based disease modeling and treatment design for retinal and macular degeneration.

Applicants should have received PhD or M.D./PhD within the last two years in Biochemistry, Genetics, Cell, Development, Molecular Biology, Bioinformatics, or similar fields. Only candidates with a strong motivation and publication record, as well as excellent communication and inter-personal skills will be considered. Annual stipend will be commensurate with experience and training.

Interested applicants should submit a cover letter with a description of career goals, curriculum vitae with publications, and contact information of 3 references to Dr. Charlie Drinnan at charlie.drinnan@nih.gov.

The NIH is dedicated to building a diverse community in its training and employment programs. DHHS, NIH, and NEI are Equal Opportunity Employers.

Selected publications

2019

Improved retinal organoid differentiation by modulating signaling pathways revealed by comparative transcriptome analyses with development in vivo. Stem Cell Reports --Accepted.

Transcriptome-based molecular staging of human stem cell-derived retinal organoids uncovers accelerated photoreceptor differentiation by 9-cis retinal. Molecular Vision -- Accepted.

Retinal disease in ciliopathies: Recent advances with a focus on stem cell-based therapies. Translational Science of Rare Diseases. DOI:10.3233/TRD-190038.

Assessment of Novel Genome-Wide Significant Gene Loci and Lesion Growth in Geographic Atrophy Secondary to Age-Related Macular Degeneration. JAMA Ophthalmol. PMID:31120506.

Age-related changes of the retinal microvasculature. PLoS One. PMID:31048908.

The combination of whole-exome sequencing and clinical analysis allows better diagnosis of rare syndromic retinal dystrophies. Acta Ophthalmol. PMID:30925032.

Retinal Transcriptome and eQTL Analyses Identify Genes Associated with Age-Related Macular Degeneration. Nature Genet. PMID:30742112.

Association of Age-Related Macular Degeneration with Complement Activation Products, Smoking, and Single Nucleotide Polymorphisms in South Carolinians of European and African Descent. Mol. Vision. PMID:30820144.

2018

Mitochondrial Respiration in Outer Retina Contributes to Light-Evoked Increase in Hydration In Vivo. Invest. Ophthalmol. Vis. Sci. PMID:30551203.

Targeted Deletion of an NRL- and CRX-regulated Alternative Promoter Specifically Silences FERM and PDZ Domain Containing 1 (Frmpd1) in Rod Photoreceptors. Human Mol. Genetic. PMID:30445545.

A CEP290 C-Terminal Domain Complements the Mutant CEP290 of Rd16 Mice In Trans and Rescues Retinal Degeneration. Cell Reports. PMID:30332642.

Mini and Customized Low-Cost Bioreactors for Optimized High-Throughput Generation of Tissue Organoids. Stem Cell Investigation. PMID:30498744.

Molecular Dissection of Cone Photoreceptor‐enriched Genes Encoding Transmembrane and Secretory Proteins. J. Neurosci. Res. PMID:30260491.

Cone-rod Homeobox CRX Controls Presynaptic Active Zone Formation in Photoreceptors of Mammalian Retina. Human Mol. Genetic. PMID:30084954.

Patient iPSC-derived Neural Stem Cells exhibit Phenotypes in Concordance with the Clinical Severity of Mucopolysaccharidosis I. Human Mol. Genet. PMID:30052969.

Postnatal Developmental Dynamics of Cell Type Specification Genes in Brn3a/Pou4f1 Retinal Ganglion Cells. Neural Dev. 2018;13(1):15. PMID:29958540.

Epigenetic Control of Gene Regulation during Development and Disease: A View from the Retina. Prog Retin Eye Res. 2018:S1350-9462(17)30104-0. PMID:29544768.

RNA Biology in Retinal Development and Disease. Trends Genet. 2018;34(5):341-351. PMID:29395379.

Genome-wide Analysis of Disease Progression in Age-related Macular Degeneration. Hum Mol Genet. 2018;27(5):929-940. PMID:29346644.

Accelerated and Improved Differentiation of Retinal Organoids from Pluripotent Stem Cells in Rotating-Wall Vessel Bioreactors. Stem Cell Reports. 2018;10(1):300-313. PMID:29233554.

2017

Accelerated and Improved Differentiation of Retinal Organoids from Pluripotent Stem Cells in Rotating-Wall Vessel Bioreactors. Stem Cell Reports. 2018;10(1):300-313. PMID:29233554.

Molecular Anatomy of the Developing Human Retina. Dev Cell. 2017;43(6):763-779. PMID:292334770.

In Vitro Modeling Using Ciliopathy-Patient-Derived Cells Reveals Distinct Cilia Dysfunctions Caused by CEP290 Mutations. Cell Rep. 2017;20(2):384-396. PMID:28700940.

Pias3 is necessary for dorso-ventral patterning and visual response of retinal cones but is not required for rod photoreceptor differentiation. Biol Open. 2017;6(6):881-890. PMID:28495965.

REEP6 mediates trafficking of a subset of Clathrin-coated vesicles and is critical for rod photoreceptor function and survival. Hum Mol Genet. 2017;26(12):2218-2230. PMID:28369466.

Nrl knockdown by AAV-delivered CRISPR/Cas9 prevents retinal degeneration in mice. Nat Commun. 2017;8:14716. PMID:28291770.

2016

NRL-Regulated Transcriptome Dynamics of Developing Rod Photoreceptors. Cell Rep. 2016;17(9):2460–2473. PMID:27880916.

Recruitment of Rod Photoreceptors from Short-Wavelength-Sensitive Cones during the Evolution of Nocturnal Vision in Mammals. Dev Cell. 2016;37(6):520-32. PMID:27326930.

Next generation sequencing technology and genomewide data analysis: Perspectives for retinal research. Prog Retin Eye Res. 2016;55:1-31. PMID:27297499.

Centrosomal protein CP110 controls maturation of the mother centriole during cilia biogenesis. Development. 2016;143(9):1491-501. PMID:26965371.

2015

Quantification of Oxygen Consumption in Retina Ex Vivo Demonstrates Limited Reserve Capacity of Photoreceptor Mitochondria. Invest Ophthalmol Vis Sci. 2015;56(13):8428-36. PMID:26747773.

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. Nat Genet. 201648(2):134-43. PMID:26691988.

Transcriptome Dynamics of Developing Photoreceptors in Three-Dimensional Retina Cultures Recapitulates Temporal Sequence of Human Cone and Rod Differentiation Revealing Cell Surface Markers and Gene Networks. Stem Cells. 2015;33(12):3504–3518. PMID:26235913.

2014

Ciliopathy-associated gene Cc2d2a promotes assembly of subdistal appendages on the mother centriole during cilia biogenesis. Nat Commun. 2014;5:4207. PMID:24947469.

Rare and common variants in extracellular matrix gene Fibrillin 2 (FBN2) are associated with macular degeneration. Hum Mol Genet. 2014;23(21): 5827–5837. PMID:24899048.

Age-Related Macular Degeneration: Genetics and Biology Coming Together. Annu Rev Genomics Hum Genet. 2014;15:151–171. PMID:24773320.

Regulation of a novel isoform of Receptor Expression Enhancing Protein REEP6 in rod photoreceptors by bZIP transcription factor NRL. Hum Mol Genet. 2014; 23(16): 4260–4271. PMID:24691551.

The transcription-splicing protein NonO/p54nrb and three NonO-interacting proteins bind to distal enhancer region and augment rhodopsin expression. Hum Mol Genet. 2014;23(8):2132-44. PMID:24301678.

Ancestry estimation and control of population stratification for sequence-based association studies. Nat Genet. 2014;46(4):409-15. PMID:24633160.

More information

Retinal Development, Genetics and Therapy Section key staff

Key staff table
Name Title Email Phone
Anand P. Swaroop, Ph.D. Senior Investigator and Lab Chief swaroopa@nei.nih.gov 301-435-5754
Andrew Smith, Ph.D. Postdoctoral Fellow andrew.smith3@nih.gov 301-827-6098
Anupam Mondal, Ph.D. Postdoctoral Fellow anupam.mondal@nih.gov 301-443-5132
Benjamin Fadl, B.S. Graduate Student benjamin.fadl@nih.gov 301-827-4216
Catherine Jaeger, Ph.D. Postdoctoral Fellow catherine.jaeger@nih.gov 301-827-6095
Coco (Ke) Jiang, Ph.D. Postdoctoral Fellow coco.jiang@nih.gov 301-443-5169
Holly Chen, Ph.D. Research Fellow holly.chen@nih.gov 301-443-7820
James Gentry, B.S. Postbaccalaureate Student james.gentry@nih.gov 301-451-6439
Jayshree Advani, Ph.D. Postdoctoral Fellow jayshree.advani@nih.gov 301-443-7406
Koray Kaya, Ph.D. Research Fellow koraydogan.kaya@nih.gov 301-827-4815
Laura Campello, Ph.D. Postdoctoral Fellow laura.campello@nih.gov 301-827-6093
Lina Zelinger, Ph.D. Postdoctoral Fellow lina.zelinger@nih.gov 301-451-6440
Michael Phelan, B.S. Graduate Student michael.phelan2@nih.gov 301-443-5132
Mrinal Dewanjee, Ph.D. Special Volunteer mrinal.dewanjee@nih.gov 301-443-0416
Nivedita Singh, Ph.D. Postdoctoral Fellow nivedita.singh@nih.gov 301-443-7406
Noor White, Ph.D. Postdoctoral Fellow noor.white@nih.gov 301-402-5734
Partha Dey, Ph.D. Postdoctoral Fellow deypn@nei.nih.gov 301-402-5755
Ryan Strickland, B.S. Postbaccalaureate Student ryan.strickland@nih.gov 301-443-5791
Samantha Papal, Ph.D. Research Fellow samantha.papal@nih.gov 301-443-5791
Scott Henke, Ph.D. Postdoctoral Fellow scott.henke@nih.gov 301-443-2917
Ximena Corso-Díaz, Ph.D. Postdoctoral Fellow ximena.corsodiaz@nih.gov 301-451-6439
Xulong Liang, Ph.D. Postdoctoral Fellow liangx6@nih.gov 301-443-7399
Last updated: October 2019