By developing new ways to probe the relationship between genotype and phenotype, Douglas Fowler seeks to determine how changes in genome sequences influence disease risk, prognosis and treatment, and how gene expression patterns combine with protein activity to define cellular processes such as growth, migration and communication.
His lab draws on expertise in genomics, protein science, technology development and computational approaches. Fowler and his team developed deep mutational scanning, a sequencing-based, multiplex genetic assay for quantifying the consequences of hundreds of thousands of mutations in a protein simultaneously. Subsequently, they worked to improve and then apply deep mutational scanning to disease-related genes. Due to Fowler and his team, deep mutational scanning has become widely used; laboratories around the world have collectively revealed the effects of millions of mutations in a large number of proteins. Fowler’s team has also developed new tools for precisely controlling genome editing, revealing the dynamics of DNA cleavage and repair. The ultimate aim is to probe the effect of every possible mutation in the human genome, paving the way for the use of genomic information in the clinic.
New Investigator Research Grant, Alzheimer’s Association
Ruth L. Kirchstein National Research Service Award, National Institutes of Health/NIGMS
Harold M. Weintraub Award, Fred Hutchinson Cancer Research Center
Starita, L.M. et al. "Variant interpretation: functional data to the rescue." American Journal of Human Genetics 101 (2017): 315–25.
Rose, J.C. et al. "Rapidly inducible Cas9 and DSB-ddPCR to probe editing kinetics." Nature Methods 14, no. 9 (2017): 891–96.
Matreyek, K.A., J.J. Stephany, and D.M. Fowler. "A platform for functional assessment of large variant libraries in mammalian cells." Nucleic Acids Research 45, no. 11 (June 2017): e102.
Fowler, D.M., and S. Fields. "Deep mutational scanning: a new style of protein science." Nature Methods 11 (2014): 801–07.