research

We study the untapped repertoire of alternatively spliced antiviral genes. Nearly all human genes are alternatively spliced, and a major driver of host-specific protein differences can be traced to it. Influenza virus is our model system for exploring how infection triggers changes in alternative splicing, and how the resulting host factors — pro-viral or antiviral — are regulated after transcription.

Can hosts hide antiviral genes inside essential ones?

Viruses commonly exploit essential genes for pro-viral activities. We found that the metabolic enzyme MECR contains an alternatively spliced isoform that liberates it from the mitochondria to target the flu polymerase directly. It’s a hint that hosts may safeguard antiviral proteins by embedding them within genes a virus can’t afford to disrupt. → Alternative splicing liberates a cryptic cytoplasmic isoform of mitochondrial MECR that antagonizes influenza virus, PLOS Biology

Why does ANP32A from birds stimulate flu polymerase, but the human version doesn’t?

ANP32A is a critical host determinant: the avian version stimulates avian-adapted influenza polymerase, but human ANP32A does not. We’re working out how ANP32A functions mechanistically, and whether certain bird species may “pre-adapt” circulating avian influenza viruses before they ever reach a human host. → Natural ANP32A splice variants differentially stimulate the flu polymerase, Cell Reports · ANP32B, or not to be, that is the question, eLife Insight

Why don’t influenza A and B viruses reassort?

Reassortment — swapping whole genome segments between co-infecting viruses — is a major driver of influenza diversity. Influenza A and B viruses (FLUAV and FLUBV) both infect and cause disease in humans, but they don’t reassort with each other. We found that incompatible viral packaging signals are what keeps the two species apart. → Journal of Virology

Building better tools to watch it all happen

Bulky reporter proteins often come with fitness costs when engineered into a virus. Our tandem split-GFP approach strings GFP11 fragments together to boost brightness while minimizing the hit to viral fitness — a tool we and others can use to watch splicing-linked host factors in action during a real infection. → Tandem split-GFP influenza viruses are fit & bright, Spectrum

For a full list of publications, see Google Scholar or NCBI Bibliography.