Memorial Sloan Kettering Cancer Center New York, New York
Professor and Member, Developmental Biology Program Professor Weill Graduate School of Medical Sciences, Cornell University
Understanding the evolution of BRCA-related breast cancers and identifying targeted prevention strategies.
Inherited mutations in genes, including BRCA1 and BRCA2, that are involved in DNA damage repair significantly increase the risk of breast and other cancers. Events that occur during specific stages of mammary development can also alter the lifetime risk of breast cancer. Dr. Jasin is working to understand how developmental changes unique to the mammary gland affect the DNA repair processes, particularly in BRCA mutation carriers, to identify new targets for drug development and prevention.
Dr. Jasin is testing whether high levels of estrogen, such as during normal mammary gland development, impair normal DNA replication in mammary cells. To that end, she and her team measured indicators of replication stress in DNA, a sign of insufficient DNA damage repair. She found that mammary cells at the pubertal stage experience more replication stress compared to those at the adult stage. Dr. Jasin also showed that estrogen can trigger replication stress in BRCA2-deficient cells. Her team is using 3-D mammary cell cultures to understand the molecular intricacies of the replication stress response during mammary gland development.
Dr. Jasin will continue to expand her earlier work by performing experiments with BRCA2 mutant cells at different developmental stages to gain a better understanding of how the loss of BRCA2 function affects breast tissues from puberty to adulthood. They will also examine whether progesterone, another hormone abundant in the mammary cells during development, may have similar effects on DNA replication stress. Results from this work will illuminate the relationship between the effects of hormone-driven replication stress and BRCA2 function in protecting the genome.
Maria Jasin is an investigator at Memorial Sloan Kettering Cancer Center and the Weill Cornell Graduate School of Medical Sciences, New York. She obtained her Ph.D. from the Massachusetts Institute of Technology, and was a postdoctoral researcher at the University of Zürich and Stanford University prior to joining the faculty at MSKCC.
Her research focuses on the repair of DNA breaks in chromosomes in several contexts, including during gamete development, in chromosomal translocation formation, and for gene editing, where her lab performed the first such experiment. Her understanding of DNA repair mechanisms, in particular, homologous recombination, led her laboratory to studies of the cellular roles of the breast cancer suppressors BRCA1 and BRCA2. Her studies found that both proteins are critical for homologous recombination to repair DNA breaks. Mechanistically, however, the proteins act at different steps in the pathway, such that BRCA1 and BRCA2 tumors are predicted to have both distinct and overlapping second site mutations that affect therapy resistance. Moreover, her laboratory has provided insight into the critical occurrence of replication stress arising from loss of BRCA2 and the involvement of p53. Given the high predisposition to breast cancers, a current research focus is to understand DNA repair in the breast at different developmental stages and contexts. Her research accomplishments have led to election to the National Academies of Sciences and Medicine and the American Academy of Arts and Sciences.
2017
The Estée Lauder Companies’ North American Research & Development and Supply Chain Award
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