We focus on DNA replication and repair, and the roles of these pathways on cancer initiation, progression and response to chemotherapy. The environment of our laboratory offers a unique combination of biochemical, cellular, and structural approaches that is ideal for the training of students and postdoctoral fellows interested in studying the mechanisms responsible for the maintenance of genome integrity. We are one of the few labs worldwide that combines biochemical, cellular, and electronic microscopy approaches to study perturbations of replication fork dynamics at single-molecule resolution. Using these technologies, we made seminal contributions toward the understanding of central pathways by which DNA replication responds to DNA-damaging chemotherapy. Specifically, we identified key determinants required for replication fork reversal that allows replication forks to reverse their course when they face DNA lesions. We also elucidated mechanisms of replication fork repriming that allows replication forks to skip lesions introduced by DNA-damaging agents, leaving a single stranded DNA (ssDNA) gap between the lesion and the point where DNA synthesis resumes. Moreover, we uncovered the post-replicative mechanisms in charge of repairing the ssDNA gaps that form upon repriming. Importantly, ssDNA gaps have recently emerged as key determinants for genome stability and chemotherapy response. Our findings provided key insights on how to target these gap repair pathways to increase chemotherapy sensitivity. Going forward, we seek to further dissect the molecular mechanisms driving the cancer cell response to chemotherapeutics. These studies are paramount not only to develop novel and more effective chemotherapeutic strategies, but also to understand why efficacy of DNA damaging chemotherapy is frequently hampered by the development of chemoresistance. In particular, we will exploit the knowledge emerging from our mechanistic studies to test whether mutations or changes in the expression level of factors involved in replication fork stability may be linked to development of chemoresistance in cancer cells carrying mutations in DNA repair genes. In addition to our research, we are part of the newly established Siteman Center for Genome Integrity that fosters interactions and new collaborations between clinical and basic research scientists working on closely-related areas of DNA damage response, DNA replication and repair, chromatin biology, and gene regulation. 

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Our lab is proud to be composed of a diverse community of scientists fascinated by the mechanisms that connect DNA and people together! We have trained 17 graduate students, 18 postdoctoral researchers, and over 25 undergraduate students from different nationalities and underrepresented minorities. In addition to our commitment to team science, we have a genuine interest in welcoming folks with diverse backgrounds and perspectives with the goal of fostering everyone's individual growth.