David is from Iowa City, Iowa. He attended Iowa City City High School where he played soccer and was introduced to human genetics through a program that placed high school students in research labs at the University of Iowa. He worked for geneticist Brian Schutte PhD, and later spent two summers in the lab of Jeff Murray MD, where he first learned how to sequence DNA and heard about the human genome project. After high school, David left Iowa for Seattle, Washington to attend college at the University of Washington. He earned a B.S. in Biochemistry and worked for four years in the UW Genome Center studying the genome of the opportunistic gram-negative bacterial pathogen, Pseudomonas aeruginosa , where he was a co-author on the paper describing the Pseudomonas reference genome, and lead author of a study that used genome sequencing to compare Pseudomonas isolates collected from evironmental sources and patients with cystic fibrosis. After graduating, David spent one year as a Research Technician in the lab of genome mapping pioneer Maynard V. Olson PhD before joining the UW MSTP training program. His graduate studies took place in the new Department of Genome Sciences that was formed from the Departments of Genetics and Molecular Biotechnology with co-mentors Maynard and fellow human genome pioneer Bob Waterston (both of whom came to the UW from the Department of Genetics at Wash U). David’s thesis work was on the development and application of methods to sequence and analyze large regions of the human genome. This included developing an efficient method for identifying potentially pathogenic mutations using principles of population genetics, and one of the first studies to use hybridization-capture to identify disease-causing mutations in the human genome. After completing his MD and PhD, David and his family moved to St. Louis for residency training in Clinical Pathology and a fellowship in Molecular Genetic Pathology at Washington University/Barnes-Jewish Hospital in St. Louis, Missouri. There David helped to develop one of the first clinical NGS assays for detecting cancer mutations. Following residency and fellowship, he did post-doctoral research in the laboratory of renowned cancer biologist Tim Ley, where he studied the genomics and epigenomics of acute myeloid leukemia (AML). He led studies that defined the effects of decitabine treatment on DNA methylation in primary AML samples, identified functional differences between AML subclones, investigated the epigenetic mechanisms involved in HOX gene regulation in normal hematopoiesis and AML, and characterized the landscape of DNA methylation changes that occur in primary AML samples with mutations in the de novo DNA methyltransferase DNMT3A.
David started his own lab at Wash U in 2016. The overarching goal of his research is to improve the genetic diagnosis of AML and our understanding of its molecular pathogenesis at the level of the genome. His lab studies the regulation of the HOX gene family and how the chromatin regulator CTCF organizes the three-dimensional structure of the HOX locus and influences functional interactions with regulatory enhancers in normal hematopoietic cells and in AML. He also studies patterns of DNA methylation in AML and how these changes relate to recurrent mutations, and the mechanisms by which altered DNA methylation influences genome architecture and gene regulation. David directs the CLIA-Licensed Environment clinical sequencing laboratory at the McDonnell Genome Institute, which supports clinical trials involving sequencing of tumor samples, including AML. The laboratory also performs sequencing of patient samples for clinical tests available at Washington University, including clinical gene panel assays for solid tumors and myeloid malignancies, whole exome sequencing of tumors for tumor vaccine studies, and targeted sequencing for inherited diseases. David is also a co-developer of ChromoSeq, a clinical whole genome sequencing assay for genomic profiling of AML and MDS, which is currently in use for routine diagnostic testing of all AML patients at Barnes-Jewish Hospital in St. Louis. His work has been supported by grants from the National Cancer Institute, the American Society of Hematology, the American Cancer Society, The Cancer Research Foundation, and The Doris Duke Charitable Foundation.