Joshua L. Dunaief, MD, PhD

faculty photo
Associate Professor of Ophthalmology
Department: Ophthalmology
Graduate Group Affiliations

Contact information
305 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

Selected Publications

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.

He Lizhi, Marioutina Mariya, Dunaief Joshua L, Marneros Alexander G: Age- and gene-dosage-dependent cre-induced abnormalities in the retinal pigment epithelium. The American journal of pathology 184(6): 1660-7, Jun 2014.

Masuda Tomohiro, Wahlin Karl, Wan Jun, Hu Jianfei, Maruotti Julien, Yang Xue, Iacovelli Jared, Wolkow Natalie, Kist Ralf, Dunaief Joshua L, Qian Jiang, Zack Donald J, Esumi Noriko: Transcription factor SOX9 plays a key role in the regulation of visual cycle gene expression in the retinal pigment epithelium. The Journal of biological chemistry 289(18): 12908-21, May 2014.

Song Delu, Zhao Liangliang, Li Yafeng, Hadziahmetovic Majda, Song Ying, Connelly John, Spino Michael, Dunaief Joshua L: The oral iron chelator deferiprone protects against systemic iron overload-induced retinal degeneration in hepcidin knockout mice. Investigative ophthalmology & visual science 55(7): 4525-32, 2014.

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 2014 Notes: in press.

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

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 2014 Notes: in press.

Fuqua Brie K, Lu Yan, Darshan Deepak, Frazer David M, Wilkins Sarah J, Wolkow Natalie, Bell Austin G, Hsu JoAnn, Yu Catherine C, Chen Huijun, Dunaief Joshua L, Anderson Gregory J, Vulpe Chris D: The multicopper ferroxidase hephaestin enhances intestinal iron absorption in mice. PloS one 9(6): e98792, 2014.

Chen Yong, Khan Reas S, Cwanger Alyssa, Song Ying, Steenstra Catherine, Bang Sookhee, Cheah Jaime H, Dunaief Joshua, Shindler Kenneth S, Snyder Solomon H, Kim Sangwon F: Dexras1, a small GTPase, is required for glutamate-NMDA neurotoxicity. The Journal of neuroscience : the official journal of the Society for Neuroscience 33(8): 3582-7, Feb 2013.

Hadziahmetovic M, Pajic M, Grieco S, Song Y, Song D, Li Y, Cwanger A, Iacovelli J, Chu S, Ying G, Connelly J, Spino M, Dunaief, JL: The oral iron chelator deferiprone protects against retinal degeneration induced through diverse mechanisms. Translational Vision Science and Technology 1(3): 2, Oct 2012 Notes: eCollection 2012.

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Last updated: 08/05/2014
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