Joshua L. Dunaief, MD, PhD
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
422 Curie Blvd.
Philadelphia, PA 19104-6100
Office: 215-898-5235
Fax: 215-573-3918
Fax: 215-573-3918
Email:
jdunaief@mail.med.upenn.edu
jdunaief@mail.med.upenn.edu
Graduate Group Affiliations
Publications
Education:
B.A. (Biology)
Harvard University (magna cum laude), 1987.
PhD (Microbiology)
Columbia University, 1994.
MD
Columbia University, 1996.
B.A. (Biology)
Harvard University (magna cum laude), 1987.
PhD (Microbiology)
Columbia University, 1994.
MD
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.
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.
Certifications
American Board of Ophthalmology, 2001.
American Board of Ophthalmology, re-certified, 2011.
Permanent linkAmerican Board of Ophthalmology, 2001.
American Board of Ophthalmology, re-certified, 2011.
Description of Research Expertise
Research InterestsMechanisms 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 for 2010-2011
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
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.
Zhao,C, Yasumura,D, Li,X, Matthes,M, Lloyd,M, Nielsen,G, Ahern,K, Snyder,M, Bok,D, Dunaief,JL, LaVail,M, Vollrath,D. : mTOR-Mediated Dedifferentiation of the Retinal Pigment Epithelium Initiates Photoreceptor Degeneration in Mice. Journal of Clinical Investigation 121(1): 369-383, Jan 2011.
Hadziahmetovic, M, Song Y, Ponnuru, P, Iacovelli, J, Hunter, A, Haddad, N, Beard, J, Connor, J, Vaulont, S, and Dunaief, J: Age-dependent retinal iron accumulation and degeneration in Hepcidin knockout mice. Investigative Ophthalmology and Visual Science 52: 109-118, Jan 2011.
Leed MG, Wolkow N, Pham DM, Daniel CL, Dunaief JL, Franz KJ: Prochelators triggered by hydrogen peroxide provide hexadentate iron coordination to impede oxidative stress J Inorg Biochem. 105: 1161-72, 2011.
Wolkow N, Song Y, Wu TD, Qian J, Guerquin-Kern JL, Dunaief JL: Aceruloplasminemia: retinal histopathologic manifestations and iron-mediated melanosome degradation. Archives of Ophthalmology 129: 1466-74, 2011.
Hadziahmetovic, M., Song, Y., Wolkow, N., Iacovelli, J., Kautz, L., Roth, M-P., Dunaief, J.L. : Bmp6 Regulates Retinal Iron Homeostasis and Has Altered Expression in Age-Related Macular Degeneration. American Journal of Pathology 179: 335-48, 2011.
Mehta S, Bunya VY, Orlin SE, Sulewski ME, Dunaief JL: A significant drug-drug interaction detected through corneal examination: resolution of cornea verticillata while using amiodarone. Cornea 31: 81-3, 2011.
Xu W, Grunwald JE, Metelitsina TI, DuPont JC, Ying GS, Martin ER, Dunaief JL, Brucker AJ: Association of risk factors for choroidal neovascularization in age-related macular degeneration with decreased foveolar choroidal circulation. Am J Ophthalmol 150(1): 40-47, Jul 2010.
