The Lieberman laboratory studies the innate and adaptive immune response to infection and cancer. They seek to understand how cytotoxic T lymphocytes and NK cells provide immune protection in some conditions and fail to function or cause immune pathology in others, focusing on understanding the molecular pathways killer cells deploy to kill both mammalian cells and microbes. They study the molecular pathways used by killer lymphocytes and their cytotoxic granule proteases, called granzymes, and pore-forming proteins, perforin and granulysin, that induce programmed cell death. Recent work has identified an unexpected role for granzymes and granulysin in protection against bacteria and parasites. Her lab was the first to describe CD8 T cell exhaustion in humans, which is the basis for current checkpoint blockade therapies for treating cancer. Her laboratory also identified the mechanism behind inflammatory death (pyroptosis) triggered by innate immune recognition of pathogens and danger signals and the role of pyroptosis in infection and cancer. They showed that pyroptosis is triggered by cleavage of a family of proteins called gasdermins, which then form cell membrane pores that disrupt cell membrane integrity. Recent work has identified important roles for pyroptosis in SARS-CoV-2, Yersinia, and Group A streptococcal infections. Current work focuses on innate and adaptive immune responses to invasive pathogens, including bacteria, malaria and other parasites, including the role of decidual NK cells in protection against infection in pregnancy.
The Lieberman laboratory has also been in the forefront of developing RNAi-based therapeutics and using RNAi for genome-wide screening. They were the first to show that siRNAs could be used to treat disease in vivo, a strategy that has already led to 5 FDA-approved drugs, and to develop cell-targeted RNAs that selectively knockdown gene expression in vivo in immune cells and cancer cells. They have developed strategies for cell-targeted RNAi to treat viral infection, immune disease and cancer. They are currently studying how cancer cell immunoediting enables tumor cells to evade immune control and are developing aptamer-directed siRNAs and epigenetic modifiers as novel strategies to reverse immunoediting and expand the range of cancer cells that respond to immunotherapy.
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