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Department
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Hematology/Oncology
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Hospital Title
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Senior Investigator, CBR Institute
for Biomedical Research
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Academic Title
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Professor of Pediatrics
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Phone
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617-278-3106
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Fax
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617-278-3134
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Email
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Judy Lieberman
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Location
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CBR Institute for Biomedical Research
200 Longwood Avenue
Boston MA 02115
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The Lieberman laboratory studies the molecular pathways used by cytotoxic T cells and natural killer cells to induce death of virus infected cells or tumors. They have defined a novel form of programmed cell death induced by the most abundant cytotoxic granule serine protease, granzyme A. This caspase-independent cell death pathway has all the morphological features of apoptosis but involves single-stranded DNA damage, not double stranded DNA breaks. It does not involve caspase activation or share substrates with the caspases, and cells that are resistant to the caspase pathway, such as by overexpressing bcl-2, are sensitive to granzyme A. Granzyme A activates a novel form of mitochondrial damage without cytochrome c release. A special target of this cell death pathway is an oxidative stress response complex, called the SET complex, which contains DNA repair enzymes and proteins involved in chromatin modification and transcriptional activation in response to oxidative stress. A key focus is to understand the normal function of the SET complex and its potential role in cellular transformation and the response to stress and DNA damage. Recent work is also aimed at understanding the biochemical and cell biological basis for the function of perforin, the membrane-perturbing protein that delivers the CTL granzyme proteases into cells. The Lieberman laboratory also studies how CTL function is regulated in the setting of chronic infection, with a particular emphasis on HIV infection.
The Lieberman laboratory was the first to demonstrate in an animal model that RNA interference (RNAi) could be used to protect animals from disease. Her laboratory is actively working to harness RNAi for therapeutic use for HIV and other indications and has developed novel strategies for cell-specific targeting of small interfering RNAs that are effective in vivo. The lab is also investigating the role of the endogenous microRNA pathway in hematopoietic cell differentiation, cellular transformation and viral infection.
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Dr. Lieberman received a PhD from Rockefeller University and an MD in the Harvard-MIT Program in Health, Science and Technology. She completed a residency and heme-onc fellowship at Tufts-New England Medical Center and a postdoctoral fellowship in immunology at MIT.
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- Palliser D, Chowdhury D, Wang, Q-Y, Lee SJ, Bronson RT, Knipe DM, and Lieberman J. An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection. Nature 2006; 439:89-94.
- Chowdhury D, Keogh MC, Ishii H, Peterson CL, Buratowski S and Lieberman J. γ-H2AX Dephosphorylation by Protein Phosphatase 2A Facilitates DNA Double Strand Break Repair. Mol Cell 2005; 20:801-809.
- Song E, Zhu P, Lee S-K, Chowdhury D, Kussman S, Dykxhoorn DM, Feng Y, Palliser D, Weiner DB, Shankar P, Marasco WA, Lieberman J. Antibody-mediated delivery of small interfering RNAs via cell surface receptors. Nature Biotech 2005; 9:347-351.
- Keefe D, Shi L, Feske S, Massol R, Navarro F, Kirchhausen T, Lieberman J. Perforin triggers a plasma membrane-repair response that facilitates CTL induction of apoptosis. Immunity 2005; 23:249-262.
- Z Fan, PJ Beresford, DY Oh, D Zhang, J Lieberman, Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL mediated apoptosis, and the nucleosome assembly protein SET is its inhibitor, Cell 2003; 112:659-672.
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