NIH Director’s Wednesday Afternoon Lecture Series

The Lieberman laboratory has been in the forefront of developing RNAi-based therapeutics and using RNAi for genome-wide screening. The lab was the first to demonstrate that siRNAs could protect mice from disease. Dr. Lieberman and her lab developed methods to harness RNAi to inhibit herpes and HIV transmission in animal models. They have developed strategies for cell-targeted RNAi to treat viral infection, immune disease, and cancer. They are currently investigating tumor-targeted siRNAs for immunotherapy to activate tumor expression of neoantigens and avoid autoimmune side effects of checkpoint inhibitors. The lab is also investigating the role of endogenous microRNAs and lncRNAs in regulating cell differentiation and cancer.

In particular, Dr. Lieberman and her colleagues study cytotoxic T lymphocytes and their role in infection and tumor immunity. Her lab investigates the molecular pathways used by killer lymphocytes and their cytotoxic granule proteases (granzymes) and pore-forming proteins (perforin and granulysin) to induce programmed cell death. The lab has defined a caspase-independent programmed-cell-death pathway activated by granzyme A. Recent work has identified an unexpected role for granzymes and granulysin: protecting against bacteria and parasites. Dr. Lieberman and her lab recently uncovered the molecular basis for inflammatory cell death (pyroptosis) triggered by invasive bacteria and other danger signals. They found that the inflammatory caspase-cleaved protein (gasdermin D) causes cell death due to the formation of membrane pores. This mechanism also directly kills the bacteria that trigger the inflammasome. Current work focuses on innate and adaptive immune responses to invasive pathogens, including bacteria, malaria, other parasites, and fungi, including the role of decidual natural killer cells in protection against infection in pregnancy.

This Khoury lecture was organized by NIH scientists to honor the memory of cancer virologist George Khoury, M.D., who was highly regarded as a superb scientist and caring mentor of the postdoctoral fellows in his laboratory. Dr. Khoury, former chief of the Laboratory of Molecular Virology at the National Cancer Institute, was known for his instinctive inquisitive nature, unfaltering kindness, self-giving mentorship, and exceptional science.

For more information go to https://oir.nih.gov/wals