Neff obtained her Ph.D. at the University of California, Berkeley, where she focused on the mechanism of termination of transcription by bacterial RNA polymerase. As a Damon Runyon Postdoctoral Fellow at MIT with David Botstein, she acquired expertise in yeast molecular genetics and subsequently demonstrated that homologous recombination could knock out genes and introduce new sequences. She then joined the faculty of Memorial Sloan Kettering Cancer Center, where her lab isolated the first yeast protein to have two distinct enzymatic activities associated with the extein and intein created by a protein self-splicing event. At Stanford University, she established a sequencing program for the Stem Cell Institute and played a central role in the development of novel whole-genome sequencing techniques, single-cell RNA-seq and genome sequencing, and the application of sequencing to liquid biopsy-based diagnostics. As director of the Genomics Platform at CZ Biohub, Neff manages sequencing services, continues work on single-molecule sequencing, and participates in the development of novel diagnostics.