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Joshua L. Dunaief, MD, PhD

Joshua L. Dunaief, MD, PhD

faculty photo
Adele Niessen Professor of Ophthalmology
Department: Ophthalmology
Graduate Group Affiliations

Contact information
305B Stellar Chance
422 Curie Blvd.
Philadelphia, PA 19104-6100
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 Clinical Expertise

age-related macular degeneration (AMD)

Selected Publications

Song Delu, Song Jiantao, Wang Chenguang, Li Yafeng, Dunaief Joshua L: Berberine protects against light-induced photoreceptor degeneration in the mouse retina. Experimental eye research 145: 1-9, Oct 2015.

Theurl Milan, Song Delu, Clark Esther, Sterling Jacob, Grieco Steve, Altamura Sandro, Galy Bruno, Hentze Matthias, Muckenthaler Martina U, Dunaief Joshua L: Mice with hepcidin-resistant ferroportin accumulate iron in the retina. FASEB journal : official publication of the Federation of American Societies for Experimental Biology Oct 2015 Notes: Epub ahead of prin.

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.

Bhoiwala Devang L, Dunaief Joshua L: Retinal abnormalities in β-thalassemia major. Survey of ophthalmology Aug 2015 Notes: Epub ahead of prin.

Zhao Liangliang, Hadziahmetovic Majda, Wang Chenguang, Xu Xueying, Song Ying, Jinnah H A, Wodzinska Jolanta, Iacovelli Jared, Wolkow Natalie, Krajacic Predrag, Weissberger Alyssa Cwanger, Connelly John, Spino Michael, Lee Michael K, Connor James, Giasson Benoit, Leah Harris Z, Dunaief Joshua L: Cp/Heph mutant mice have iron-induced neurodegeneration diminished by deferiprone. Journal of neurochemistry Aug 2015 Notes: Epub ahead of prin.

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 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.

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Last updated: 12/23/2015
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