University of Pennsylvania Health System

Department of Ophthalmology

Ophthalmology Faculty

Faculty Overview

Joshua L. Dunaief, MD, PhD

faculty photo
Adele Niessen Professor of Ophthalmology
Member, Institute of Neuroscience, University of Pennsylvania, University of Pennsylvania
Member, Neuroscience Graduate Group, University of Pennsylvania, University of Pennsylvania
Scientist, F.M. Kirby Center for Molecular Ophthalmology, University of Pennsylvania
Member, Institute on Aging, University of Pennsylvania, University of Pennsylvania
Member, Cell and Molecular Biology Graduate Group, University of Pennsylvania, University of Pennsylvania
Department: Ophthalmology

Contact information
305 Stellar Chance
422 Curie Blvd.
Philadelphia, PA 19104-6100
Graduate Group Affiliations
B.A. (Biology)
Harvard University (magna cum laude), 1987.
PhD (Microbiology)
Columbia University, 1994.
Columbia University, 1996.
Post-Graduate Training
Intern in Internal Medicine, Mercy Hospital/University of Maryland, 1996-1997.
Resident in Ophthalmology, Wilmer Eye Institute, The Johns Hopkins Hospital, Baltimore, 1997-2000.
Medical Retina Fellowship, Scheie Eye Institute, University of Pennsylvania, 2000-2004.
American Board of Ophthalmology, 2001.
American Board of Ophthalmology, re-certified, 2011.
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Description of Research Expertise

Research Interests
Mechanisms of oxidative stress induced apoptosis in the retina

Key words: AMD, iron, oxidative stress, apoptosis, retina, aging, mitochondria.

Description of Research
Age related macular degeneration (AMD) is the most common cause of irreversible blindness, yet its pathogenesis is poorly understood. Evidence suggests that cumulative oxidative damage contributes to AMD and aging in general. My lab has found that AMD retinas have iron overload, which can increase oxidative stress. Increased understanding of retinal iron homeostasis may lead to treatments for AMD. To investigate the mechanisms of retinal iron regulation, we use transgenic mouse models, human retinal tissue, and a dual chamber tissue culture system to study iron transport. A mouse line deficient in the iron transporting ferroxidases ceruloplasmin and hephaestin develops age-dependent retinal iron overload and retinal degeneration with features of AMD (Hahn et al., PNAS, 2004). Recent research suggests that iron plays a key role in apoptosis induced by a variety of insults. Further investigation of the mechanisms of retinal iron homeostasis and of iron induced apoptosis are the focus of the lab.

Rotation Projects
1)Study mechanisms of retinal iron regulation by performing histology and immunofluorescence on retinal sections from transgenic and knockout mice. You will learn retinal anatomy and the techniques of ocular microdissection, cryosectioning, plastic sectioning and microscopy.

2)Test the potentially protective effects of iron chelators on cultured retinal cells. You will learn tissue culture, qPCR, and cell death assays.

Lab personnel:
Majda Hadziahmetovic, postdoc
Ying Song, research specialist
Jared Iacovelli, graduate student
Allan Hunter, K12 fellow
Natalie Wolkow, MD/PhD student
Steve Grieco, research assistant
Alyssa Cwanger, research assistant
Jennifer Lee, research assistant
Sally Chu, undergraduate student

Description of Clinical Expertise

age-related macular degeneration (AMD)

Selected Publications

Li Y, Song D, Song Y, Zhao L, Wolkow N, Tobias JW, Song W, Dunaief JL: Iron-induced Local Complement Component 3 (C3) Up-regulation via Non-Canonical TGF-β Signaling in the Retinal Pigment Epithelium. Journal Biol Chem 290(19): 11918-34, May 2015.

Choi Soo Young, Baek Jeong-In, Zuo Xiaofeng, Kim Seok-Hyung, Dunaief Joshua L, Lipschutz Joshua H: Cdc42 and sec10 Are Required for Normal Retinal Development in Zebrafish. Invest Ophthalmol Vis Sci 56(5): 3361-70, May 2015.

Jiang Ruiwei, Hua Chao, Wan Yike, Jiang Bo, Hu Huiyin, Zheng Jiashuo, Fuqua Brie K, Dunaief Joshua L, Anderson Gregory J, David Samuel, Vulpe Chris D, Chen Huijun: Hephaestin and ceruloplasmin play distinct but interrelated roles in iron homeostasis in mouse brain. J Nutr 145(5): 1003-9, May 2015.

Hunter Allan A, Smit-McBride Zeljka, Anderson Rachel, Bordbari Matthew H, Ying Gui-Shuang, Kim Esther S, Park Susanna S, Telander David G, Dunaief Joshua L, Hjelmeland Leonard M, Morse Lawrence S: GSTM1 and GSTM5 Genetic Polymorphisms and Expression in Age-Related Macular Degeneration. Curr Eye Res Page: 1-7, Apr 2015 Notes: Epub ahead of print.

Guo LY, Alekseev O, Li Y, Song Y, Dunaief JL: Iron Increases APP Translation and Amyloid-Beta Production in the Retina. Exp Eye Res 129: 31-7, Dec 2014.

Wolkow Natalie, Li Yafeng, Maminishkis Arvydas, Song Ying, Alekseev Oleg, Iacovelli Jared, Song Delu, Lee Jennifer C, Dunaief Joshua L: Iron upregulates melanogenesis in cultured retinal pigment epithelial cells. Experimental eye research 128: 92-101, Nov 2014.

Song D, Grieco S, Li Y, Hunter A, Chu S, Zhao L, Song Y, DeAngelis RA, Shi L, Liu Q, Pierce EA, Nishina PM,Lambris JD, Dunaief JL: A murine Rp1 missense mutation causing protein mislocalization and slowly progressive photoreceptor degeneration Am J Pathol 184(10): 2721-9, Oct 2014.

Zhao L, Li Y, Song D, Song Y, Theur M, Cwanger A, Su G, Dunaief JL: A High serum iron causes mouse retinal iron accumulation caused by despite an intact blood-retinal barrier Am J Pathol. Aug 2014 Notes: Epub ahead of print.

Zhao L, Wang C, Song D, Li Y, Song Y, Su G, Dunaief JL : Systemic administration of the antioxidant/iron chelator alpha lipoic acid protects against light-induced photoreceptor degeneration in the mouse retina Invest Ophthalmol Vis Sci 55(9): 5979-88, Aug 2014.

Song Delu, Grieco Steve, Li Yafeng, Hunter Allan, Chu Sally, Zhao Liangliang, Song Ying, DeAngelis Robert A, Shi Lan-Ying, Liu Qin, Pierce Eric A, Nishina Patsy M, Lambris John D, Dunaief Joshua L: A Murine Rp1 Missense Mutation Causes Protein Mislocalization and Slowly Progressive Photoreceptor Degeneration. The American journal of pathology Jul 2014.

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Last updated: 06/02/2015
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