Joshua L. Dunaief

faculty photo
Associate 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.
Permanent link

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

Hadziahmetovic Majda, Kumar Usha, Song Ying, Grieco Steven, Song Delu, Li Yafeng, Tobias John W, Dunaief Joshua L: Microarray Analysis of Murine Retinal Light Damage Reveals Changes in Iron Regulatory, Complement, and Antioxidant Genes in the Neurosensory Retina and Isolated RPE. Investigative ophthalmology & visual science 53(9): 5231-41, Sep 2012.

Song Delu, Song Ying, Hadziahmetovic Majda, Zhong Yong, Dunaief Joshua L: Systemic administration of the iron chelator deferiprone protects against light-induced photoreceptor degeneration in the mouse retina. Free radical biology & medicine 53(1): 64-71, Jul 2012.

Tarallo Valeria, Hirano Yoshio, Gelfand Bradley D, Dridi Sami, Kerur Nagaraj, Kim Younghee, Cho Won Gil, Kaneko Hiroki, Fowler Benjamin J, Bogdanovich Sasha, Albuquerque Romulo J C, Hauswirth William W, Chiodo Vince A, Kugel Jennifer F, Goodrich James A, Ponicsan Steven L, Chaudhuri Gautam, Murphy Michael P, Dunaief Joshua L, Ambati Balamurali K, Ogura Yuichiro, Yoo Jae Wook, Lee Dong-ki, Provost Patrick, Hinton David R, Núñez Gabriel, Baffi Judit Z, Kleinman Mark E, Ambati Jayakrishna: DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88. Cell 149(4): 847-59, May 2012.

Hunter Allan, Spechler Paul A, Cwanger Alyssa, Song Ying, Zhang Zhe, Ying Gui-Shuang, Hunter Anna K, Dezoeten Edwin, Dunaief Joshua L: DNA methylation is associated with altered gene expression in AMD. Investigative ophthalmology & visual science 53(4): 2089-105, Apr 2012.

Wolkow Natalie, Song Delu, Song Ying, Chu Sally, Hadziahmetovic Majda, Lee Jennifer C, Iacovelli Jared, Grieco Steven, Dunaief Joshua L: Ferroxidase hephaestin's cell-autonomous role in the retinal pigment epithelium. The American journal of pathology 180(4): 1614-24, Apr 2012.

Mehta Sonia, Bunya Vatinee Y, Orlin Stephen E, Sulewski Michael E, Dunaief Joshua L: A significant drug-drug interaction detected through corneal examination: resolution of cornea verticillata while using amiodarone. Cornea 31(1): 81-3, Jan 2012.

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 in press, 2012.

Hiroki, K, Sami D, Tarallo, V, Fowler, B, Gelfand, B, Cho, W, Kleinman, M, Ponicsan, S, Hauswirth, W, Chiodo, V, Kariko, K, Yoo, J, Lee, D, Hadziahmetovic, M, Song, Y, Chaudhuri, G, Buaas, F, Braun, Hinton, D, Zhang, Q, Grossniklaus, H, Provis, J, Madigan, M, Milam, A, Justice, N., Romulo,Albuquerque, J, Blandford, A., Bogdanovich, S, Hirano, Y, Witta, J, Fuchs, E, Littman, D, Ambati, B, Rudin, C, Chong, M, Provost, P, Kuge, J, Goodrich, J, Dunaief, JL, Baffi, J, Ambati, J: DICER1 dysregulation induces cytotoxic Alu RNA accumulation in age-related macular degeneration. Nature 471(7338): 325-330, Mar 2011.

Iacovelli,J, Zhao,C, Wolkow,N, Veldman,P, Gollomp,K, Ojha,P, Lukinova,N, King,A, Feiner,L, Esumi,N, Zack,D, Pierce,E, Vollrath,D, Dunaief,JL: Generation of cre transgenic mice with postnatal RPE-specific ocular expression. Investigative Ophthalmology and Visual Science 52(3): 1378-1383, Mar 2011.

Hadziahmetovic, M, Song, Y, Wolkow, N, Iacovelli, J, Grieco, Lee, J, Lyubarsky, A, Pratico, D, Connelly, J, Spino, M, Harris, ZL, Dunaief, JL: Oral iron chelator deferiprone protects against iron overload induced retinal degeneration. Investigative Ophthalmology and Visual Science 52(2): 959-968, Feb 2011.

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Last updated: 05/15/2014
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