Judy Lieberman, MD, PhD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 713-8600
Fax: (617) 713-8621


Judy Lieberman, MD, PhD

Boston Children's Hospital


  • Professor, Pediatrics, Harvard Medical School
  • Chair, PCMM, Boston Children's Hospital


Research Abstract

The Lieberman laboratory studies cytotoxic T lymphocytes, key cells in the immune defense against viral infection and cancer, and their role in antiviral immunity.

A major focus of the Lieberman laboratory is studying the molecular pathways used by CTLs to induce cell death. Granzyme A, the most abundant CTL death-inducing protease, induces a novel form of programmed cell death. Many tumors and viruses resistant to the classical pathway of cell death are sensitive to this pathway. The Lieberman laboratory has identified several novel protein substrates of granzyme A and has recently worked out the molecular basis for DNA destruction in this pathway.

Other work centers on understanding how the function of cytotoxic T lymphocytes is regulated. Her laboratory is particularly interested in characterizing the cytotoxic T lymphocyte response to HIV-1, the virus that causes AIDS, and why it does not ultimately control the virus. They have found that although there are a large number of HIV-specific T cells in HIV-infected individuals, their function is significantly compromised in vivo. Knowledge gained from laboratory studies is used to develop and test in small clinical studies immune-based therapeutic and preventive strategies to treat HIV-infection. Currently her laboratory is working to develop an oral HIV vaccine using a Listeria monocytogenes vector.

Her interest in HIV led to recent work to harness RNA interference (RNAi) as a therapeutic tool. Her laboratory was able to harness this ancient antiviral defense mechanism, originally described in plants and worms, but more recently in mammalian cells, to suppress HIV infection. She was the first to demonstrate in an animal model that RNAi could be used to protect animals from disease. Her laboratory is currently actively working on translating RNAi for therapeutic use for HIV and cancer.

More recently they have been studying how miRNAs regulate cell differentiation and cancer. A recent paper from the Lieberman laboratory identified the miRNA let-7 as a master regulator of stemness of breast cancer stem cells. They are currently working to define the pathways by which let-7 and other miRNAs regulate self-renewal, differentiation, cell division, metastasis and chemosensitivity. They are also working to translate these findings into approaches for cancer therapy.


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  • O'Day E, Le MT, Imai S, Tan SM, Kirchner R, Arthanari H, Hofmann O, Wagner G, Lieberman J. An RNA-binding Protein, Lin28, Recognizes and Remodels G-quartets in the MicroRNAs (miRNAs) and mRNAs It Regulates. J Biol Chem 2015; 290:17909-22. PubMed
  • Lieberman J. Manipulating the in vivo immune response by targeted gene knockdown. Curr Opin Immunol 2015; 35:63-72. PubMed
  • Thomas MP, Liu X, Whangbo J, McCrossan G, Sanborn KB, Basar E, Walch M, Lieberman J. Apoptosis Triggers Specific, Rapid, and Global mRNA Decay with 3' Uridylated Intermediates Degraded by DIS3L2. Cell Rep 2015; 11:1079-89. PubMed
  • Luo ML, Gong C, Chen CH, Hu H, Huang P, Zheng M, Yao Y, Wei S, Wulf G, Lieberman J, Zhou XZ, Song E, Lu KP. The Rab2A GTPase Promotes Breast Cancer Stem Cells and Tumorigenesis via Erk Signaling Activation. Cell Rep 2015. PubMed
  • Navarro F, Lieberman J. miR-34 and p53: New Insights into a Complex Functional Relationship. PLoS ONE 2015; 10:e0132767. PubMed
  • Dotiwala F, Fellay I, Filgueira L, Martinvalet D, Lieberman J, Walch M. A High Yield and Cost-efficient Expression System of Human Granzymes in Mammalian Cells. 2015. PubMed
  • Sharei A, Trifonova R, Jhunjhunwala S, Hartoularos GC, Eyerman AT, Lytton-Jean A, Angin M, Sharma S, Poceviciute R, Mao S, Heimann M, Liu S, Talkar T, Khan OF, Addo M, von Andrian UH, Anderson DG, Langer R, Lieberman J, Jensen KF. Ex vivo cytosolic delivery of functional macromolecules to immune cells. PLoS ONE 2015; 10:e0118803. PubMed
  • Le MT, Hamar P, Guo C, Basar E, Perdigão-Henriques R, Balaj L, Lieberman J. miR-200-containing extracellular vesicles promote breast cancer cell metastasis. J Clin Invest 2014; 124:5109-28. PubMed
  • Tan SM, Kirchner R, Jin J, Hofmann O, McReynolds L, Hide W, Lieberman J. Sequencing of captive target transcripts identifies the network of regulated genes and functions of primate-specific miR-522. Cell Rep 2014; 8:1225-39. PubMed
  • Tay Y, Tan SM, Karreth FA, Lieberman J, Pandolfi PP. Characterization of dual PTEN and p53-targeting microRNAs identifies microRNA-638/Dnm2 as a two-hit oncogenic locus. Cell Rep 2014; 8:714-22. PubMed
  • Luo ML, Gong C, Chen CH, Lee DY, Hu H, Huang P, Yao Y, Guo W, Reinhardt F, Wulf G, Lieberman J, Zhou XZ, Song E, Lu KP. Prolyl Isomerase Pin1 Acts Downstream of miR200c to Promote Cancer Stem-like Cell Traits in Breast Cancer. Cancer Res 2014. PubMed
  • Thomas MP, Whangbo J, McCrossan G, Deutsch AJ, Martinod K, Walch M, Lieberman J. Leukocyte Protease Binding to Nucleic Acids Promotes Nuclear Localization and Cleavage of Nucleic Acid Binding Proteins. J Immunol 2014. PubMed
  • Thiery J, Lieberman J. Perforin: a key pore-forming protein for immune control of viruses and cancer. Subcell. Biochem. 2014; 80:197-220. PubMed
  • Tuli A, Thiery J, James AM, Michelet X, Sharma M, Garg S, Sanborn KB, Orange JS, Lieberman J, Brenner MB. Arf-like GTPase Arl8b regulates lytic granule polarization and natural killer cell-mediated cytotoxicity. Mol Biol Cell 2013; 24:3721-35. PubMed
  • Petrocca F, Altschuler G, Tan SM, Mendillo ML, Yan H, Jerry DJ, Kung AL, Hide W, Ince TA, Lieberman J. A genome-wide siRNA screen identifies proteasome addiction as a vulnerability of basal-like triple-negative breast cancer cells. Cancer Cell 2013; 24:182-96. PubMed
  • Thomas MP, Lieberman J. Live or let die: posttranscriptional gene regulation in cell stress and cell death. Immunol Rev 2013; 253:237-52. PubMed
  • Huang L, Jin J, Deighan P, Kiner E, McReynolds L, Lieberman J. Efficient and specific gene knockdown by small interfering RNAs produced in bacteria. Nat Biotechnol 2013; 31:350-6. PubMed
  • Lieberman J, Slack F, Pandolfi PP, Chinnaiyan A, Agami R, Mendell JT. Noncoding RNAs and cancer. Cell 2013; 153:9-10. PubMed
  • Lieberman J, Sarnow P. Micromanaging Hepatitis C Virus. N Engl J Med 2013. PubMed
  • Lee MN, Roy M, Ong SE, Mertins P, Villani AC, Li W, Dotiwala F, Sen J, Doench JG, Orzalli MH, Kramnik I, Knipe DM, Lieberman J, Carr SA, Hacohen N. Identification of regulators of the innate immune response to cytosolic DNA and retroviral infection by an integrative approach. Nat Immunol 2013; 14:179-85. PubMed
  • Yan N, Lieberman J. SAMHD1 does it again, now in resting T cells. Nat Med 2012; 18:1611-2. PubMed
  • Thomas M, Lieberman J, Lal A. Desperately seeking microRNA targets. Nat Struct Mol Biol 2010; 17:1169-74. PubMed
  • Thiery J, Walch M, Jensen DK, Martinvalet D, Lieberman J. Isolation of cytotoxic T cell and NK granules and purification of their effector proteins. Curr Protoc Cell Biol 2010; Chapter 3:Unit3.37. PubMed
  • Navarro F, Lieberman J. Small RNAs guide hematopoietic cell differentiation and function. J Immunol 2010; 184:5939-47. PubMed
  • Lieberman J. Anatomy of a murder: how cytotoxic T cells and NK cells are activated, develop, and eliminate their targets. Immunol Rev 2010; 235:5-9. PubMed
  • Lieberman J. Granzyme A activates another way to die. Immunol Rev 2010; 235:93-104. PubMed
  • Thiery J, Keefe D, Saffarian S, Martinvalet D, Walch M, Boucrot E, Kirchhausen T, Lieberman J. Perforin activates clathrin- and dynamin-dependent endocytosis, which is required for plasma membrane repair and delivery of granzyme B for granzyme-mediated apoptosis. Blood 2010; 115:1582-93. PubMed
  • Chan MC, Hilyard AC, Wu C, Davis BN, Hill NS, Lal A, Lieberman J, Lagna G, Hata A. Molecular basis for antagonism between PDGF and the TGFbeta family of signalling pathways by control of miR-24 expression. EMBO J 2010; 29:559-73. PubMed
  • Lieberman J. Micromanaging cancer. N Engl J Med 2009; 361:1500-1. PubMed
  • Lal A, Navarro F, Maher CA, Maliszewski LE, Yan N, O'Day E, Chowdhury D, Dykxhoorn DM, Tsai P, Hofmann O, Becker KG, Gorospe M, Hide W, Lieberman J. miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to "seedless" 3'UTR microRNA recognition elements. Mol Cell 2009; 35:610-25. PubMed
  • Navarro F, Gutman D, Meire E, Cáceres M, Rigoutsos I, Bentwich Z, Lieberman J. miR-34a contributes to megakaryocytic differentiation of K562 cells independently of p53. Blood 2009; 114:2181-92. PubMed
  • Ahmed F, Friend S, George TC, Barteneva N, Lieberman J. Numbers matter: quantitative and dynamic analysis of the formation of an immunological synapse using imaging flow cytometry. J Immunol Methods 2009; 347:79-86. PubMed
  • Zhu P, Martinvalet D, Chowdhury D, Zhang D, Schlesinger A, Lieberman J. The cytotoxic T lymphocyte protease granzyme A cleaves and inactivates poly(adenosine 5'-diphosphate-ribose) polymerase-1. Blood 2009; 114:1205-16. PubMed
  • Petrocca F, Lieberman J. Micromanipulating cancer: microRNA-based therapeutics? RNA Biol 2009; 6:335-40. PubMed
  • Lal A,Pan Y,Navarro F,Dykxhoorn DM,Moreau L,Meire E,Bentwich Z,Lieberman J,Chowdhury D. miR-24-mediated downregulation of H2AX suppresses DNA repair in terminally differentiated blood cells. Nat Struct Mol Biol 2009; 16:492-8. PubMed
  • Yan N,Cherepanov P,Daigle JE,Engelman A,Lieberman J. The SET complex acts as a barrier to autointegration of HIV-1. PLoS Pathog 2009; 5:e1000327. PubMed
  • Wu Y,Navarro F,Lal A,Basar E,Pandey RK,Manoharan M,Feng Y,Lee SJ,Lieberman J,Palliser D. Durable protection from Herpes Simplex Virus-2 transmission following intravaginal application of siRNAs targeting both a viral and host gene. Cell Host Microbe 2009; 5:84-94. PubMed
  • Petrocca F,Lieberman J. Chapter 4 micromanagers of immune cell fate and function. Adv Immunol 2009; 102:227-44. PubMed
  • Dykxhoorn DM, Wu Y, Xie H, Yu F, Lal A, Petrocca F, Martinvalet D, Song E, Lim B, Lieberman J. miR-200 enhances mouse breast cancer cell colonization to form distant metastases. PLoS ONE 2009; 4:e7181. PubMed
  • Shun MC,Botbol Y,Li X,Di Nunzio F,Daigle JE,Yan N,Lieberman J,Lavigne M,Engelman A. Identification and characterization of PWWP domain residues critical for LEDGF/p75 chromatin binding and human immunodeficiency virus type 1 infectivity. J Virol 2008; 82:11555-67. PubMed
  • Petrocca F,Lieberman J. RIG-ing an antitumor response. Nat Med 2008; 14:1152-3. PubMed
  • Chowdhury D, Xu X, Zhong X, Ahmed F, Zhong J, Liao J, Dykxhoorn DM, Weinstock DM, Pfeifer GP, Lieberman J. A PP4-phosphatase complex dephosphorylates gamma-H2AX generated during DNA replication. Mol Cell 2008; 31:33-46. PubMed
  • Martinvalet D,Dykxhoorn DM,Ferrini R,Lieberman J. Granzyme A cleaves a mitochondrial complex I protein to initiate caspase-independent cell death. Cell 2008; 133:681-92. PubMed
  • Brass AL, Dykxhoorn DM, Benita Y, Yan N, Engelman A, Xavier RJ, Lieberman J, Elledge SJ. Identification of host proteins required for HIV infection through a functional genomic screen. Science 2008; 319:921-6. PubMed
  • Dykxhoorn DM, Chowdhury D, Lieberman J. RNA interference and cancer: endogenous pathways and therapeutic approaches. Adv Exp Med Biol 2008; 615:299-329. PubMed
  • Chowdhury D, Lieberman J. Death by a thousand cuts: granzyme pathways of programmed cell death. Annu Rev Immunol 2008; 26:389-420. PubMed
  • Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, Huang Y, Hu X, Su F, Lieberman J, Song E. let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell 2007; 131:1109-23. PubMed
  • Jiang S, Rasmussen RA, Nolan KM, Frankel FR, Lieberman J, McClure HM, Williams KM, Babu US, Raybourne RB, Strobert E, Ruprecht RM. Live attenuated Listeria monocytogenes expressing HIV Gag: immunogenicity in rhesus monkeys. Vaccine 2007; 25:7470-9. PubMed
  • Lee-Kirsch MA, Gong M, Chowdhury D, Senenko L, Engel K, Lee YA, de Silva U, Bailey SL, Witte T, Vyse TJ, Kere J, Pfeiffer C, Harvey S, Wong A, Koskenmies S, Hummel O, Rohde K, Schmidt RE, Dominiczak AF, Gahr M, Hollis T, Perrino FW, Lieberman J, Hubner N. Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus. Nat Genet 2007; 39:1065-7. PubMed
  • Glodek AM, Le Y, Dykxhoorn DM, Park SY, Mostoslavsky G, Mulligan R, Lieberman J, Beggs HE, Honczarenko M, Silberstein LE. Focal adhesion kinase is required for CXCL12-induced chemotactic and pro-adhesive responses in hematopoietic precursor cells. Leukemia 2007; 21:1723-32. PubMed
  • de Fougerolles A, Vornlocher HP, Maraganore J, Lieberman J. Interfering with disease: a progress report on siRNA-based therapeutics. Nat Rev Drug Discov 2007; 6:443-53. PubMed
  • Pipkin ME, Lieberman J. Delivering the kiss of death: progress on understanding how perforin works. Curr Opin Immunol 2007; 19:301-8. PubMed
  • Chowdhury D, Beresford PJ, Zhu P, Zhang D, Sung JS, Demple B, Perrino FW, Lieberman J. The exonuclease TREX1 is in the SET complex and acts in concert with NM23-H1 to degrade DNA during granzyme A-mediated cell death. Mol Cell 2006; 23:133-42. PubMed
  • Lieberman J, Sharp PA. Harnessing RNA interference for therapy: the silent treatment. JAMA 2015; 313:1207-8. PubMed
  • Hata A, Lieberman J. Dysregulation of microRNA biogenesis and gene silencing in cancer. Sci Signal 2015; 8:re3. PubMed