Genomic dissection of mRNA decay, from mechanism to clinical applications
Co-translational mRNA decay provides a unique window into ribosome dynamics and cellular adaptation. By sequencing 5’P mRNA degradation intermediates (5PSeq), we can map the in vivo position of the last translating ribosome, enabling high-resolution studies of mRNA decay and translation coupling. 

I will discuss our recent work demonstrating that, under nutrient limitation, the majority of the transcriptome undergoes -1 ribosome frameshifting, triggering accelerated out-of-frame mRNA decay via nonsense-mediated decay (NMD). This process, driven by low codon optimality, is evolutionarily conserved from bacteria to yeast and humans and serves as a molecular mechanism to limit cell growth under stress.
 

Next, I will present how 5PSeq and related metadegradome sequencing approaches enable rapid, species-specific, post-transcriptional profiling of microbial communities. I will highlight the development of simplified, cost-effective 5PSeq protocols for rapid antimicrobial susceptibility testing (AST) and pathogen detection directly from complex samples. By leveraging ribosome dynamics as a molecular phenotype, we are advancing towards faster, more informative diagnostics for infectious diseases and antimicrobial resistance.
 

Finally, I will discuss how integrating the study of gene expression dynamics in cancer cells enables the discovery of transient, plastic cell states underlying phenotypic cancer cell plasticity. Using single-cell transcriptomics and functional genomics, we have defined transcriptional signatures of cellular plasticity that can identify plastic cells in leukemia and other cancers. These signatures are associated with metabolic reprogramming, drug resistance, and prognosis, providing new avenues for understanding and targeting cancer heterogeneity.