Eric G. Meissner, M.D., Ph.D.

Associate Professor
Department: Medicine
Program: Inflammation

 

 

Research Interests:

The Meissner laboratory’s interest is in understanding and manipulating the innate immune function of hepatocytes to guide the design of novel approaches to combat viral infections that affect the liver. Their specific focus is interferon lambda signaling, a pathway shown to be pivotal for influencing disparate clinical outcomes for persons infected with hepatitis C virus (HCV). Polymorphisms in interferon lambda genes highly associate with odds of spontaneous clearance of acute HCV infection and odds of achieving interferon-alfa mediated cure of chronic HCV infection.

The receptor for interferon lambdas (IFNLR1) is expressed on 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 peripheral immune cells including monocytes/macrophages, suggesting IFNLR1 protein isoforms are likely to 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 interferon lambdas and that manipulating relative expression of these isoforms could favorably alter the ability of hepatocytes to clear chronic hepatotropic viral infections, such as hepatitis B virus (HBV), which is currently incurable. 

Their work utilizes established in vitro cell lines (e.g. HEK293T, HEPG2, HEPG2.2.15) and induced pluripotent stem cells (iPSCs) which can be genetically manipulated and then differentiated into either hepatocyte like cells (iHeps) or macrophage like cells (iMacs). They developed iHeps and iMacs with wild-type or abrogated expression of endogenous IFNLR1 and generated clones with doxycycline-inducible expression of FLAG-tagged canonical and non-canonical IFNLR1 isoforms. Using these novel reagents, they are 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 canonical and non-canonical IFNLR1 isoforms influence the differentiation and phenotype of M0-, M1-, and M2-monocyte-derived macrophages.
• Determination of how IFNLR1 isoforms differentially traffic in the presence or absence of ligand.

 

Although Dr. Meissner’s laboratory focuses primarily on hepatocytes in relation to HBV infection, they additionally have an interest in monocyte-macrophage function as it pertains to both HBV and HIV infections.

Their laboratory makes extensive use of all the DDRCC Cores, and they have been fortunate to have already published data using them (Evans et al, Viruses, 2023; Novotny et al., Antiviral Research, 2023). In addition, the DDRCC Cores have been essential for the development of several R01 grant proposals. 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.

Publications:

PubMed Collection