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Joshua L. Dunaief, M.D., Ph.D.
Assistant Professor, Dept of Opthalmology
Cancer Biology Program
Address
305 Stellar Chance
303 Stellar Chance (Lab)
422 Curie Boulevard
Philadelphia, PA 19104-6069
Office tel.: 215 898-5235
Lab tel.: 215 898-5354
Fax: 215 573-3918
E-mail: jdunaief@mail.med.upenn.edu
Education
Harvard
College: BA (Biology), 1987.
Columbia College of Physicians and Surgeons: PhD (Microbiology: Molecular Biology of Retinoblastoma), 1994.
COlumbia College of Physicians and Surgeons: MD, 1996.
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Research
Interests
- Mechanisms of oxidative stress induced apoptosis in the retina
Key words: AMD, iron, oxidative stress, apoptosis, retina, aging, mitochondria
Search PubMed for articles
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.
Recent
Publications
Chowers I, Wong R, Dentchev T, Farkas RH, Iacovelli
J, Gunatilaka TL, Medeiros NE, Presley JB, Campochiaro PA,
Curcio CA, Dunaief JL, Zack DJ. The iron
carrier transferrin is upregulated in retinas from patients
with age-related macular degeneration. Invest Ophthalmol
Vis Sci. 2006 May;47(5):2135-40.
Dunaief JL, Richa C, Franks
EP, Schultze RL, Aleman TS, Schenck JF, Zimmerman EA, Brooks
DG. Macular degeneration in a patient with aceruloplasminemia,
a disease associated with retinal iron overload. Ophthalmology.
2005 Jun;112(6):1062-5.
Hahn P, Qian Y, Dentchev T, Chen L, Beard J,
Harris ZL, Dunaief JL. Disruption of ceruloplasmin
and hephaestin in mice causes retinal iron overload and retinal
degeneration with features of age-related macular degeneration.
Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13850-5.
Epub 2004 Sep 13.
Hahn P, Dentchev T, Qian Y, Rouault T, Harris
ZL, Dunaief JL. Immunolocalization and regulation
of iron handling proteins ferritin and ferroportin in the
retina. Mol Vis. 2004 Aug 26;10:598-607.
Dunaief, J., Strober, B., Guha,
S., Khavari, P., Alin, K., Luban, J, Begemann, M., Crabtree,
G, and Goff, S.: The Retinoblastoma protein and BRG1 form
a complex and cooperate to induce cell cycle arrest. Cell
79: 119-130, 1994.
Lab
Rotation
Projects
Recent results suggest that iron chelation confers
remarkable protection from apoptosis initiated by a variety
of insults. Lab rotations this year will focus on uncovering
the role of iron in apoptosis in cultured mammalian cells.
- Lab Personnel:
Lab photo at the Association for Research in Vision
and Ophthalmology meeting, May, 2006
The lab received the prestigious Cogan Award.
- Tzvete Dentchev, MD, Senior Research Specialist
Nina Lukinova, PhD, Senior Research Specialist
Paul Hahn, MD/PhD, post-doc and ophthamlology resident,
Scheie Eye Institute
Jared Iacovelli, MS, graduate student
Chih King, graduate student
Nick Ligato, MS, post-masters student
Xining He, post-bac student
Majda Hadziahmetovic, post-doc
Predrag Krajacic, post-doc
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