Dr. Celina Kleer studies the genetic determinants of aggressive breast cancer, translating biological findings into the development of clinically useful tissue biomarkers and more effective treatment strategies. Using cell biology, genetics, and pathology, Dr. Kleer’s laboratory unveiled a role for cellular transcriptional memory in breast carcinogenesis. These studies identified that the histone methyltransferase EZH2 is overexpressed in invasive metastatic breast carcinomas when compared with those following an indolent clinical course. Dr. Kleer has established a causal link between EZH2 and breast cancer initiation and progression, and more recently showed that EZH2 functions through noncanonical mechanisms, independent of its transcriptional repressor function. Dr. Kleer’s work has unraveled new mechanisms of breast cancer cell plasticity, particularly on the role of the microenvironment in breast cancer progression. She identified the matrix protein CCN6 as a crucial regulator of epithelial-mesenchymal transition and E-cadherin expression, and showed that CCN6 controls the tumorigenic signals that breast cells receive from their microenvironment. Dr. Kleer’s contributions are important because of their clinical relevance in predicting outcome in breast cancer patients and in the generation of new paradigms of disease pathogenesis and treatment strategies.