2023 ICIS-Pfizer Award for Excellence in Cytokine & Interferon Research (formerly the Seymour & Vivian Milstein Award from 1988 – 2020)
Judy Lieberman, MD, PhD, Professor, Pediatrics, Harvard Medical School
Endowed Chair in Cellular and Molecular Medicine, PCMM, Boston Children’s Hospital, Boston, USA Website
Judy Lieberman has been chosen for the 2023 ICIS-Pfizer Award for Excellence in Cytokine & Interferon Research in recognition of her outstanding discoveries in the field of cytokine biology, applying advances in basic science for understanding, treating and preventing human diseases through her studies on the molecular basis of killing by cytotoxic lymphocytes and pyroptotic cell death by GSDMs, the interplay between cytotoxic lymphocytes and GSDMs, and their joint roles in controlling infection and cancer.
2023 ICIS-Pfizer Award for Excellence in Cytokine & Interferon Research Presentation
Professor Lieberman will give her ICIS-Pfizer Award Presentation at Cytokines 2023 in the Opening Session on Sunday, October 15th at the Divani Caravel Hotel in Athens on “Fanning the Flames: Pyroptosis in infection, cancer and neurodegeneration”.
Professor Lieberman truly embodies the spirit of this award by being a pioneer in multiple crucial fields including RNAi based therapeutics in viral infection and cancer, molecular basis for the function of cytotoxic T cells and NK cells and her recent groundbreaking work on the inflammasome. The last illuminates how pore-forming gasdermins promote cytokine release, anti-microbial pathogens and antitumor immunity in cytotoxic T cells.
Judy Lieberman has been a leader in understanding how cytotoxic NK and T cells destroy their targets. Dr. Lieberman’s description of granzyme A-mediated cell death was the first mechanistic description of caspase-independent cell death. Her body of work related to the immune effector response illustrates a completely new dimension to programmed cell death, which inhibits the ability of a cell to recover from cytotoxic insults. Through a series of elegant studies, she revealed a caspase-3 independent cell death pathway that relies on granzymes to execute death that are induced by mitochondria and DNA damage. (PNAS 1997, Immunity 1999, JBC 2001, Cell 2003, Immunity 2005, Cell 2008). Continuing her work on the granzyme A mediated cell death pathway, she discovered that the enzyme activates a DNase, Trex1. When Trex1 is mutated, it results in hyperactivation of DNA receptors such as cGAS in cells. Defective Trex1 leads to a hereditary interferonopathy disorder called the Aicardi-Goutiere’s syndrome (PNAS 1997, JBC 2001, Cell 2003, Mol Cell 2006, J Mol Med 2007, Nat Genetics 2007, Nat Immunol 2010, Nature Immunol 2013). Trex1 is now widely acknowledged to play a crucial role in restraining DNA-sensing interferon and cytokine responses in infection, autoinflammatory diseases, autoimmunity and cancer and her contribution in the field is immense.I n her studies of how the immune system in the placenta protects against infection while maintaining fetal tolerance, she identified a new mechanism by which NK cells can kill intracellular bacteria without killing the host cell by transferring the antimicrobial peptide granulysin to trophoblasts via nanotubes [Cell, 2020].
Dr. Lieberman has shown that another cytotoxic granule pore-forming protein granulysin, which is active against microbial membranes, delivers the granzymes into microbes, including bacteria and parasites, to activate rapid, programmed cell death (“microptosis”) with common features across evolutionary kingdoms [Cell, 2014; Nat Med, 2016; Nat Med, 2018; Cell, 2018]. This work defines a new immune defense against nonviral pathogens and helps explain why patients with T cell immunodeficiency and AIDS are prone to bacterial, fungal and parasite infections.
Judy has made important contributions to understanding why this immune effector response fails in the setting of chronic infection (i.e., with HIV). Her studies showed for the first time that cytotoxic T cells in most HIV- infected patients lacked expected cytotoxic and cytokine-secreting functions; thus, they have down-modulated key signaling molecules, do not activate IL-2 secretion, lack the cytolytic effector protein perforin, and do not traffic to lymphoid sites of HIV infection [Blood, 1998, 2001, 2003]. T cell exhaustion, which she described in humans for the first time at the same time R. Ahmed described it in chronic viral infection in mice, is the basis for checkpoint blockade for cancer, which is revolutionizing cancer treatment. Judy pioneered development and testing novel immunotherapy approaches before antiretroviral drugs were available to treat HIV infection [Blood, 1997], and she played a key role in developing two novel HIV vaccines – i) a detoxified anthrax toxin engineered to deliver HIV antigens; and ii) an oral vaccine using attenuated bacterium to express HIV antigens [J Virol, 2000; PNAS, 2000].
Her recent innate immunity work in infection implicates pyroptosis in the inflammatory complications of severe COVID [Nature, 2022]. Her lab showed that monocytes and macrophages are infected with SARS-CoV-2 and their infection triggers the assembly of inflammasomes, pyroptosis and release and processing of IL-1 family cytokines. Biomarkers of pyroptosis are increased in the blood of COVID patients and their increase correlates with COVID-19 disease severity. Infection of monocytes is mediated by Fc receptor uptake of antibody-coated virions, while infection of lung macrophages is mediated by both ACE2 and antibody-dependent FcR uptake. Additional work has shown both pathogenic and protective roles of pyroptosis in group A streptococcal and Yersinia bacterial infections [Science 2021, Nature 2022].
In addition, her work on granzymes, pyroptosis and gasdermins, she performed foundational research in the therapeutic use of small interfering RNA (RNAi) and was the first to show that short interfering RNAs (siRNA) could protect mice from diseases such as fulminant hepatitis (Song, E. et al., Nature Med. 2003) and herpes viral transmission when applied therapeutically (Palliser et al., Nature 2006). She also identified microRNAs that regulate a plethora of biologic functions including metastasis and DNA repair. Most impressive is her identification of new proteins and pathways in the HIV life cycle and in cancer stemness using a RNAi-based genome wide screen.
Dr. Lieberman has also performed extensive leadership roles nationally and internationally. She was a member for more than a decade of the NIH Office of AIDS Research Therapeutics Working Group, which sets national priorities on therapeutics research. She also was a key member of the Steering Committee of the Project Inform Immune Restoration Think Tank that developed strategies for immune-based therapy for HIV infection. In addition, Judy has been a long standing member of the Scientific Advisory Committee of the American Foundation for AIDS Research and also served as a consultant for the National Center for AIDS Research and Shanghai Centers for Disease Control in China and for the Comprehensive International Program for Research in AIDS in Cambodia. In 2009, she was appointed to the AIDS Research Advisory Committee (ARAC), the highest oversight committee that sets priorities for NIH-funded AIDS research. Because of her leadership in translational medicine, she was appointed in 2013 to the Scientific Advisory Board of the Massachusetts Life Sciences Center, a $1 billion initiative of the Commonwealth of Massachusetts established to promote the life sciences within the state by investing in life sciences research and economic development.
She directed numerous programs in HIV-AIDS research at Harvard University from 2003 to 2009 and has played an important role as a mentor, having mentored undergraduates and high school under-represented minorities to enter science. She trained more than 70 PhD students and postdoctoral fellows, with most remaining in academic and industry and many achieving leadership positions. Due to her outstanding contributions to science, she is the recipient of numerous awards including the ‘Hope is a Vaccine’ Award from the GAIA (Global Alliance to Immunize Against AIDS) Foundation. She also shared the prestigious William B. Coley Award in 2022 with Drs. Vishva Dixit, Hao Wu, and Feng Shao, in recognition of their groundbreaking work in the inflammasome and gasdermin field. She is an elected member of the American Academy of Arts and Sciences and National Academy of Sciences and now the recipient of the 2023 ICIS-Pfizer Award for Excellence in Cytokine & Interferon Research (formerly the Seymour & Vivian Milstein Award from 1988 – 2020).
The Pfizer Award for Excellence in Interferon and Cytokine Research (formerly the Seymour & Vivian Milstein Award from 1988 – 2020), represents the pinnacle of scientific achievement in interferon and cytokine research since 1988, two years after interferon was first approved for the treatment of hairy cell leukemia. Since that time, it has been widely recognized that interferons and the larger class of cytokines play critical roles in the development and progression of many major diseases including cancer, viral diseases such as hepatitis and influenza, and autoimmune disorders like multiple sclerosis and lupus. For more details, list of Award Laureates, please click here.
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