DNA replication is a master key to cancer growth and therapy. We focus on molecular mechanisms of DNA replication fork stability that suppress familial inherited cancers and provide a unique window on what has gone awry and the underlying disease principles. We discovered and defined replication fork protection, a major genome stability pathway. We developed and apply new methods for single cell and single molecule analyses at replication forks. Our hypotheses and efforts foremost are informed by human biology and by active collaborations with clinicians (hereditary heme, breast cancer, ovarian cancer), and our work is complemented by collaborations with bioinformaticians and structural biologists. Overall, our research aims to provide foundational knowledge to inform advanced therapeutic strategies and develop functional biomarkers to predict disease cause and response.