Our team studies how cells respond to persistent DNA damage during proliferation, focusing on checkpoint adaptation—a process where cells override DNA damage checkpoints to enter mitosis despite unresolved damage. This phenomenon contributes to genetic instability and resistance to treatments but remains poorly understood. Using advanced live-cell imaging and biosensors, we analyze checkpoint signaling dynamics in single cells to uncover mechanisms behind checkpoint adaptation and its role in genetic heterogeneity and disease.
1- Characterize replicative stress and DNA damage checkpoint signatures in High-Grade Serous Ovarian Cancer (HGSOC) by analyzing genetically defined cell line models and patient-derived tumor cells. This includes studying DNA replication perturbations, checkpoint activity, and molecular mechanisms underlying checkpoint attenuation, leveraging advanced biosensors and collaborations to link these signatures with specific driver mutations.
2- Investigate how replicative stress and DNA damage checkpoint profiles influence the sensitivity of HGSOC cells to checkpoint inhibitors, such as ATR and Chk1/2 inhibitors. By using biosensors to monitor kinase activity and drug specificity, we aim to elucidate mechanisms of drug response and resistance, ultimately improving the prediction and effectiveness of targeted therapies based on tumor genetic contexts.
