Virology Faculty Member - Judy Lieberman

Judy Lieberman

Professor of Pediatrics

Boston Children's Hospital
Program in Cellular and Molecular Medicine
Warren Alpert Bldg., Rm. 255
200 Longwood Ave.
Boston, MA 02115
Tel: 617-713-8600
Fax: 617 713-8620
Email: judy.lieberman@childrens.harvard.edu



The Lieberman laboratory studies cytotoxic T lymphocytes (CTLs) and their role in antiviral immunity. It focuses on the molecular pathways used by CTLs to induce programmed cell death, especially those activated by the granzymes, cytotoxic granule proteases. Recent work identified an important role for NK cells and T cells in antibacterial immunity. The lab seeks to understand how bacteria are killed and what sorts of bacteria are targeted. They are also studying how apoptosis disrupts post-transcriptional RNA processing. The lab has shown that granzyme A targets the SET complex, a chromatin modifying and DNA repair complex mobilized in response to oxidative stress, which contains the granzyme A-activated DNases. One goal is to understand the normal function of the SET complex in cells. They showed that the SET complex binds to HIV reverse transcripts and enables HIV to evade triggering innate immunity. It also plays an important role in systemic lupus erythematosis and other autoimmune/inflammatory syndromes.

Ever since RNA interference (RNAi) was shown to operate in mammalian cells, the Lieberman laboratory has been in the forefront of developing RNAi-based therapeutics. They were the first to demonstrate that siRNAs could protect mice from disease when they showed that silencing the death receptor fas prevented a fatal form of hepatitis. They also showed that RNAi could be used to inhibit HIV infection by silencing both viral and host genes essential for infection. They developed a method for using siRNAs as the active ingredient of a topical microbicide to prevent spread of sexually transmitted diseases and showed protection against vaginal transmission of lethal herpes simplex virus type 2 in mice and HIV transmission in humanized mice. They also developed methods for targeted cell-specific systemic siRNA administration to lymphocytes and epithelial cancer cells. They are developing this approach to modulate immune responses that are harmful (such as in autoimmunity or transplant rejection or sepsis) and for use as a microbicide to prevent HIV transmission. They are also developing RNAi-based treatment for cancer.

They are also investigating the role of endogenous microRNAs in regulating viral infection and cancer. They identified microRNAs that regulate self-renewal and tumorigenesis of breast cancer initiating cells (or cancer stem cells), enhance metastasis and that block growth factor signaling, cell division, or DNA damage repair. They have developed methods to identify the genes regulated by a microRNA to understand how cancer-related microRNAs function They are also investigating whether microRNAs can be transmitted via exosomes to affect cancer growth and metastasis.



Last Update: 10/22/2013



Publications

1. Lal A, Navarro F, Maher C, Maliszewski LE, Yan N, O’Day E, Chowdhury D, Dykxhoorn DM, Tsai P, Hofman O, Becker KG, Gorospe M, Hide W and Lieberman J. miR-24 inhibits cell proliferation by targeting E2F2, MYC and other cell cycle genes by binding to “seedless” 3’UTR microRNA recognition elements. Mol Cell 2009; 35:610-625.

2. Yan N, Regalado-Magdos, AD, Stiggelbout B, Lee-Kirsch MA and Lieberman J. The cytosolic exonuclease TREX1 inhibits the innate immune response to human immunodeficiency virus type 1. Nature Immunol 2010; 11:1005-1013.

3. Thiery J, Keefe D, Boulant S, Boucrot E, Walch M, Martinvalet D, Goping IS, Bleackley RC, Kirchhausen T and Lieberman J. Perforin pores in the endosomal membrane trigger release of granzyme B to the cytosol of target cells. Nature Immunol 2011; 12:770-777.

4. Huang L, Jin J, Deighan P, Kiner E, McReynolds L and Lieberman J. Efficient and specific gene knockdown by small interfering RNAs produced in bacteria. Nature Biotech 2013; 31:350-356.



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