The Meissner laboratory’s interest is in understanding mechanisms of lambda interferon signaling with an aim towards using this knowledge to design new therapeutic approaches for treatment of viral infections. Lambda interferon lambda signaling is pivotal for influencing disparate clinical outcomes for persons infected with hepatitis C virus (HCV), however the mechanisms of lambda interferon signaling and how variability in these mechanisms may differ between individuals to influence disparate infection outcomes are not fully understood.
The receptor for lambda interferon (IFNLR1) is expressed on epithelial cells, including hepatocytes, but at a very low level making it difficult to detect using protein-based biochemistry detection techniques (i.e. Western blot, immunofluorescence, flow cytometry). Distinct transcriptional IFNLR1 isoforms suggestive of alternative splicing have been detected in hepatocytes as well as in peripheral immune cells, suggesting IFNLR1 protein isoforms may play a role in pathway regulation. The overarching hypothesis of the Meissner lab is that these IFNLR1 isoforms influence the innate immune response of hepatocytes exposed to either endogenous or exogenously administered interferon lambdas and that manipulating expression of these isoforms could favorably alter the ability of the innate immune response to clear viral infections, for example hepatitis B virus (HBV) infection.
Their work utilizes established in vitro cell lines and induced pluripotent stem cells (iPSCs) which can be genetically manipulated and then differentiated into different cell types, for example hepatocyte like cells (iHeps) . Using iHeps with intact or abrogated expression of endogenous IFNLR1 and doxycycline-inducible expression of FLAG-tagged canonical and non-canonical IFNLR1 isoforms, the lab is dissecting how each IFNLR1 isoform functions in the context of innate immunity in both uninfected and HBV-infected settings. Specific questions the Meissner lab is addressing include the following:
- Determination of how IFNLR1 isoforms differentially influence gene expression of hepatocytes treated with lambda interferons.
- Evaluation of how non-canonical IFNLR1 isoforms require or do not require endogenous IFNLR1 expression to function.
- Determination of how manipulation of IFNLR1 isoform expression influences the capacity of lambda interferons to inhibit HBV replication and promote cccDNA degradation.
- Determination of how IFNLR1 isoforms differentially traffic in the presence or absence of ligand.
The Meissner laboratory uses multiple DDRCC Cores extensively which has supported their recent publications (Evans et al, Viruses, 2023; Novotny et al., Antiviral Research, 2024; Novotny et al., Journal of Interferon and Cytokine Research, 2025; Novotny et al., Journal of Innate Immunity 2026). The DDRCC has further been invaluable as a source of collaborators, including Drs. Duncan, Dr. Gooz, Dr. Ball, Dr. Nietert, and Dr. Mehta and as a resource for enrichment of the Dr. Meissner’s science.