Trained as a pediatrician and clinical geneticist, I have broad and enduring interests in human genetics, genomics, and clinical genetics. My bench research has long focused on understanding the molecular pathology of the chromosome instability syndromes and other rare inherited genetic disorders associated with cancer. Over the years, my laboratory has provided key evidence for how chromosome instability syndromes genes maintain genome integrity through their involvement in DNA replication, recombination, and repair, as well as DNA damage responses, and telomere maintenance.

Over 10 years ago, I developed a major clinical research interest in genomic medicine. I co-developed and served as principal investigator for the Hospital for Sick Children's Genome Clinic, a pioneering effort to demonstrate the clinical utility of genomic sequencing for the diagnosis of rare diseases. In 2018 I became the inaugural Director of the University of Wisconsin's Center for Human Genomics and Precision Medicine. As Center Director, I created and lead the UW Undiagnosed Genetic Disease Program, which takes a "beyond the exome approach"to evaluating rare disease patients, focusing on disease gene discovery and the trialing of long-read genome sequencing, epigenomic profiling, RNA-Seq, and other new diagnostic technologies.