Title: Alternative RNA splicing drives innate immune regulation and host-pathogen conflict

Steven Baker, PhD 

Assistant Professor: Molecular Genetics Microbiology, 

The University of New Mexico

Candidate for a faculty position in Virology and Vectors of Infectious Diseases in the Department of Biological Sciences

Abstract

Vertebrate cells rapidly respond to viral infection by activating >1,000 interferon-stimulated genes, creating an antiviral state that is generally unfavorable for viral infection. However, viruses rapidly evolve to adapt to hosts and immune environments and often encode antagonists that subvert host immunity. Although interferon stimulated genes are easily identified through mRNA sequencing and differential gene expression, much less is known about how alternative mRNA splicing impacts the interferon-induced transcriptome. Nearly all human genes are alternatively spliced, giving rise to multiple transcript variants per gene that often contain different functions. The Baker lab uses influenza virus infection in cell culture as a model with the ultimate goal of characterizing the innate immune RNA splicing repertoire that contributes to immunity. As part of these efforts, we identified a novel splice transcript of the immune gene ISG15 using long- and short-read RNA-sequencing. This non-canonical ISG15 variant potently restricts influenza A virus infection, but extant influenza viruses encode an antagonist that limits the antiviral activity of non-canonical ISG15. Our continued work to determine the mechanism by which non-canonical ISG15 restricts influenza and to identify novel host splicing events involved in viral infection will together unravel hidden functions of the innate immune system. By understanding the innate immune RNA splicing repertoire, we can develop new therapeutic avenues to alleviate inflammatory and infectious diseases.

Short Bio

Steve Baker was raised in Western NY, where he received his PhD at the University of Rochester. With his supervisor, Luis Martínez-Sobrido, he studied influenza virus non-coding RNA to understand virus speciation and develop laboratory tools and vaccines. Steve then went on to the University of Wisconsin to focus on host genetic determinants of influenza virus replication with Andy Mehle. Here, he began his research on the impact of host alternative RNA splicing on virus-host interactions. From 2021-2025, Dr. Baker continued research on alternative splicing through leading an independent research group at Lovelace Biomedical Research Institute, and was also appointed adjunct faculty at the University of New Mexico since 2023.

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