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The laboratory studies the molecular basis of breast cancer development and resistance to therapy, with the goal to improve precision medicine and outcomes for breast cancer patients. The laboratory employs a systems biology approach, utilizing a combination of single cell and bulk sequencing, computational methods, and biological models to identify and validate new drivers and therapeutic targets. Hypotheses are tested in vitro and in vivo and then moved to clinical trials. The majority of studies incorporate analysis of human specimens, in collaboration with a large network of clinicians and nurses. This includes computational analysis and modeling of large biomedical and genomic datasets including electronic health record data. A major goal is new model development including patient-derived organoids and patient-derived xenografts. A major focus of the laboratory is identifying mechanisms of resistance to endocrine therapy, and new approaches to blocking breast cancer metastasis through precision medicine. This includes the study of estrogen receptor (ESR1) mutations and fusions and synergism with growth factor pathways. Methods include liquid biopsies and use of a rapid autopsy program,. A special focus is on the understanding of invasive lobular cancer (ILC), the second most common but understudied histological subtype of breast cancer. The laboratory has a very strong training environment, with attention to diversity and inclusion and each individuals’ successful career development. One of the top priorities is to maintain a healthy lab environment, ensuring high productivity and rigor.