Neurobiology Neurodegeneration & Repair Laboratory (N-NRL)

Lab Chief: Anand Swaroop, Ph.D.

Building 10, Room 10B11/N248
Bethesda, Maryland 20892-1204
Phone: (301) 435-5754
Phone: (301) 435-6149
Fax: (301) 480-9917

• Mission Statement
• Research Overview
• Structure
• 2007 Publications
• Journal Covers

Mission Statement

Neurobiology Neurodegeneration & Repair Laboratory (N-NRL) was established recently with a goal to develop novel treatment modalities for blinding retinal diseases based on fundamental understanding of genetic defects and/or biological pathways underlying differentiation, homeostasis, aging and disease pathogenesis.

Research Overview

The process of vision begins in the retina. In humans, retina supplies almost 30% of the sensory input to the brain. Any damage to retinal neurons can lead to devastating consequences, including the loss of vision. Retinal and macular diseases are a major cause of visual impairment and affect the quality of life for millions worldwide. The basic premise guiding the research of this laboratory 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, this laboratory wishes to significantly advance our understanding of several fundamentally important and interrelated biological processes and help pursue clinical interventions that utilize these advances. In particular, we seek to understand: (1) how neurons differentiate from neuroepithelial progenitors (or stem cells); (2) how these neurons form functional synaptic circuits; (3) how neuronal function is accomplished in the normal retina and how it is compromised during aging and in disease conditions; and (4) how can we repair the damage or treat the degenerative disease.

We have specifically identified the following focus areas of research:

• Differentiation of Retinal Neurons from Progenitors or Stem Cells
• Synaptogenesis in the Retina
• Gene Regulatory Networks in Retinal Differentiation and Disease
• Intracellular Trafficking and Ciliopathies
• Genes and Pathways underlying Retinal Degenerative Diseases
• Genetic Variations and Functional Consequences in Retinal Aging, Age-related Macular Degeneration, and Diabetic Retinopathy
• Novel Treatment Paradigms that originate from these Investigations

The basic and clinical research environment at NIH provides unique opportunities to carry out innovative multi-disciplinary research that is critical for solving complex problems in biology and medicine. Our approach will be to build on strong and creative individual-specific projects yet tackle complex questions in retinal neurobiology and degeneration, which should lead to new cell, gene or small molecule based therapeutic paradigms. As retina is a relatively less complex and perhaps the most approachable part of the central nervous system, our research will complement the existing neuroscience programs at NIH.

Structure

The Chief of the Laboratory is Senior Investigator Dr. Anand Swaroop.

We expect to recruit several tenure-track investigators in the above focus areas over the next few years.

We encourage outstanding young scientists in all fields of biology (particularly computational and systems biology) to contact us for possible opportunities at NIH.

Name	Title	E-mail
Anand Swaroop, Ph.D.	Lab Chief, Senior Investigator	swaroopa@nei.nih.gov
Lucia Lawrence	Administrative Lab Manager	lawrencel@nei.nih.gov
Sharyn Ferrara	Administrative Lab Manager at UM (Contractor)	ferraras@nei.nih.gov
Matthew Brooks	Biologist (C)	brooksma@nei.nih.gov
Kwan-Ho Chung, Ph.D.	Postdoctoral Fellow	chungk@nei.nih.gov
Hong Cheng, M.D. , Ph.D.	Postdoctoral Fellow	chengh@nei.nih.gov
Radu Cojocaru, Ph.D.	Research Fellow	cojocarur@nei.nih.gov
James Friedman, Ph.D.	Research Fellow	friedmanja@nei.nih.gov
Linn Gieser	Biologist (Contractor)	gieserl@nei.nih.gov
Hong Hao, Ph.D.	Research Fellow	haoh@nei.nih.gov
Atsuhiro Kanda, Ph.D.	Research Fellow	kandaa@nei.nih.gov
Rajendra Kandpal, Ph.D.	Visiting Scientist	kandpalr@nei.nih.gov
Anastasia Krasnoperova	Research Assistant (Contractor)	krasnoperovaa@nei.nih.gov
Igor Nasonkin, Ph.D.	Research Fellow	nasonkini@nei.nih.gov
Jacob Nellissery, Ph.D.	Biologist	nellisseryj@nei.nih.gov
Rivka Rachel, M.D., Ph.D.	Staff Scientist	rachelr@nei.nih.gov
Jerome Roger, Ph.D.	Visiting Fellow	rogerj@nei.nih.gov
Sharda P. Yadav, Ph.D.	Visiting Fellow	yadavsh@nei.nih.gov

2007 Publications

• Swaroop A, Branham KEH, Chen W, Abecasis G: Genetic susceptibility to age-related macular degeneration: a paradigm for dissecting complex disease traits. Hum Mol Genet. 16 Spec No 2:R174-82, 2007.
• Kanda A, Chen W, Othman M, Branham KEH, Brooks M, Khanna R, He S, Lyons R, Abecasis GR*, Swaroop A*: A variant of mitochondrial protein LOC387715, not HTRA1, is strongly associated with age-related macular degeneration. Proc Natl Acad Sci. USA. 104:16227-16232, 2007.
• McEwen DP, Koenekoop RK, Khanna H, Jenkins PM, Lopez I, Swaroop A*, Martens JR*: Hypomorphic CEP290/NPHP6 mutations result in anosmia due to the loss of G-proteins in cilia of olfactory sensory neurons. Proc Natl Acad Sci. USA. 104:15917-15922, 2007.
• Oh ECT, Khan N, Novelli E, Khanna H, Strettoi E, Swaroop A: Transformation of cone precursors to functional rod photoreceptors by bZIP transcription factor NRL. Proc Natl Acad Sci USA 104:1679-1684, 2007. [Cover]
• Kanda A, Friedman JF, Nishiguchi KM, Swaroop A: Retinopathy mutations in the bZIP protein NRL alter phosphorylation and transcriptional activity. Hum Mutat. 28:589-598, 2007.
• Raven M, Oh E, Swaroop A, Reese B: Afferent control of horizontal cell morphology revealed by genetic re-specification of rods and cones. J Neurosci. 27:3540-3547, 2007.
• Trager EH, Khanna R, Marrs A, Siden L, Branham K, Swaroop A, Richards JR: Madeline 2.0 PDE: A new program for local and web-based pedigree drawing. Bioinformatics. 23:1854-1856, 2007.
• Cideciyan AV, Aleman TS, Jacobson SG, Khanna H, Sumaroka A, Aguirre GK, Schwartz SB, Windsor EAM, He S, Chang B, Stone EM and Swaroop A: Centrosomal ciliary gene CEP290/NPHP6 mutations result in blindness with unexpected sparing of photoreceptors and visual brain: implications for therapy of Leber congenital amaurosis. Hum Mutat. 28:1074-1083, 2007.
• Suzuki T, Akimoto M, Imai H, Ueda Y, Mandai M, Yoshimura N, Swaroop A, Takahashi M: Chondroitinase ABC treatment enhances synaptogenesis between transplant and host neurons in a mouse model of retinal degeneration. Cell Transplant. 16:493-503, 2007.
• Duncan JL, Zhang Y, Gandhi J, Nakanishi C, Othman M, Branham KEH, Swaroop A, Roorda A: High-resolution imaging with adaptive optics in patients with inherited retinal degeneration. Invest Ophthalmol Vis Sci. 48:3283-3291, 2007.
• Aleman TS, Cideciyan AV, Sumaroka A, Schwartz SB, Roman AJ, Windsor EAM, Steinberg JD, Branham K, Othman M, Swaroop A, Jacobson SG: Inner retinal abnormalities in X-linked retinitis pigmentosa with RPGR mutations. Invest Ophthalmol Vis Sci. 48:4759-4765, 2007.
• Chakarova CF, Papaioannou MG, Khanna H, Lopez I, Waseem N, Shah A, Theis T, Friedman J, Maubaret C, Bujakowska K, Veraitch B, El-Aziz MAM, Prescott DQ, Parapuram S, Bickmore WA, Munro PMG, Gal A, Hamel C, Marigo V, Ponting CP, Wissinger B, Zrenner E, Matter K, Swaroop A, Koenekoop RK, Bhattacharya SS: Mutations in TOPORS cause autosomal dominant retinitis pigmentosa with perivascular RPE atrophy. Am J Hum Genet. 81:1098-1103, 2007.

Journal Covers

• Proceedings of the National Academy of Sciences, January 30, 2007
• Nature, November 9, 2006
• Proceedings of the National Academy of Sciences, March 7, 2006