Joshua L. Dunaief

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
305B Stellar Chance
422 Curie Blvd.
Philadelphia, PA 19104-6100
Graduate Group Affiliations
Education:
B.A. (Biology)
Harvard University (magna cum laude), 1987.
PhD (Microbiology)
Columbia University, 1994.
MD
Columbia University, 1996.
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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 Itmat Expertise

Dr. Dunaief is studying the pathogenesis of the blinding disease age-related macular degeneration, focusing on the role of age-related iron build-up in the retina and its ability to incite inflammation and cause oxidative stress.

Selected Publications

Theurl M, Song D, Clark E, Sterling J, Grieco S, Altamura S, Galy B, Hentze M, Muckenthaler MU, Dunaief JL: Mice with hepcidin-resistant ferroportin accumulate iron in the retina. FASEB J 30(2): 813-23, Feb 2016.

Bhoiwala Devang L, Song Ying, Cwanger Alyssa, Clark Esther, Zhao Liang-liang, Wang Chenguang, Li Yafeng, Song Delu, Dunaief Joshua L: CD1 Mouse Retina Is Shielded From Iron Overload Caused by a High Iron Diet. Investigative ophthalmology & visual science 56(9): 5344-52, Aug 2015.

Zhao L, Hadziahmetovic M, Wang C, Xu X, Song Y, Jinnah HA, Wodzinska J, Iacovelli J, Wolkow N, Krajacic P, Weissberger AC, Connelly J, Spino M, Lee MK, Connor J, Giasson B, Harris ZL, Dunaief JL: Cp/Heph mutant mice have iron-induced neurodegeneration diminished by deferiprone. J Neurochem 135(5): 958-74, Dec 2015.

Gelfand Bradley D, Wright Charles B, Kim Younghee, Yasuma Tetsuhiro, Yasuma Reo, Li Shengjian, Fowler Benjamin J, Bastos-Carvalho Ana, Kerur Nagaraj, Uittenbogaard Annette, Han Youn Seon, Lou Dingyuan, Kleinman Mark E, McDonald W Hayes, Núñez Gabriel, Georgel Philippe, Dunaief Joshua L, Ambati Jayakrishna: Iron Toxicity in the Retina Requires Alu RNA and the NLRP3 Inflammasome. Cell reports 11(11): 1686-93, Jun 2015.

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 AA 3rd, Smit-McBride Z, Anderson R, Bordbari MH, Ying GS, Kim ES, Park SS, Telander DG, Dunaief JL, Hjelmeland LM, Morse LS: GSTM1 and GSTM5 Genetic Polymorphisms and Expression in Age-Related Macular Degeneration. Curr Eye Res 41(3): 410-6, 2016.

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Last updated: 07/26/2016
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