Given Dr. Isom's extensive training and broad expertise, he has a wide range of research interests and capabilities that span the fields of pharmacology, synthetic and computational biology, genetic engineering, molecular biophysics, and more. He has established an ambitious research program aimed at illuminating the molecular and cellular basis of proton sensing, creating new technologies for nanobody and drug discovery, and developing novel algorithms for data science in areas related to genomics, proteomics, and cellular imaging. Dr. Isom's research leverages his lab's ability to translate high-throughput CRISPR experiments on human genes in yeast to human cell models. This has led to advances such as new drug and nanobody discovery platforms for G protein-coupled receptors (GPCRs), the illumination of GPCR proton-sensing mechanisms, the discovery of proton-gated GPCR agonism, technologies for building fully functional GPCR biosensor chimeras, and pan-viral surveillance technologies.
More recently the lab has focused on the dark proteome, the proteins whose sequences have diverged too far for comparison to reveal what they do. By comparing predicted structures instead, the lab identified TM184C, a GPCR-like regulator of intercellular exchange and autophagy, reported in Nature in 2026. Dr. Isom calls proteins of this class superdark.??
