Dr. Paul Lehner

Biography

Paul Lehner is the Sheila Joan Smith Professor of Immunology at the Cambridge Stem Cell Institute. His research focuses on the study of novel genes and intracellular pathways involved in virus-host interactions, with particular emphasis on the epigenetic mechanisms of viral silencing. His group discovered the human silencing hub (HUSH) complex, which is an epigenetic transcriptional repressor complex that provides genome-wide surveillance against retroelement attacks. As an Infectious Diseases Physician, he investigates how life forms defend against DNA invasions that threaten genomic integrity. Mammalian cells counteract these threats by silencing incoming DNA prior to transcription. Paul emphasizes that DNA silencing through chromatinization is likely a default pathway, where viruses introduce and replicate nucleic acids, recruiting host machinery to enable their replication. Persistent viral survival hinges on evading immune recognition, which can be seen through interferon antagonism of DNA silencing. The work of his group applies genetic and proteomic technologies to understand the mechanisms of DNA silencing and how viruses overcome these pathways. Notably, his prominent discoveries include the identification of the HUSH epigenetic repressor complex, which silences incoming retroviruses and endogenous mobile retrotransposons, including LINE-1 elements, comprising over 17% of the genome. His research provides unique insights into chromatin regulation and opportunities for manipulating these pathways.

Research Interests

Experience