Maria Jasin, PhD
New York, New York
Professor, Weill Graduate School of Medical Sciences,
Member, Developmental Biology Program
Memorial Sloan Kettering Cancer Center
New York, New York
Understanding the evolution of BRCA-related breast cancers and identifying ways to prevent it.
The mammary gland is highly influenced by its hormonal environment and undergoes significant changes during puberty and pregnancy. Events that occur during specific stages of mammary development, including DNA damage, are believed to alter the lifetime risk of breast cancer. Inherited mutations in genes, including BRCA1 and BRCA2, that are involved in the cellular response to DNA damage and the repair of double-strand breaks in DNA significantly increase the risk of breast and other cancers. Dr. Jasin is working to understand how developmental changes unique to the mammary gland affect the DNA damage response and how DNA repair processes in breast calls can be manipulated to create new therapeutics to prevent breast cancer, particularly in BRCA mutation carriers.
Dr. Jasin is combining techniques in DNA repair and mammary gland biology to dissect the DNA damage response in mammary tissue to ultimately identify potential new targets for breast cancer prevention and treatment strategies. So far, Dr. Jasin and her team have successfully created mammary tissue and breast tumor 3-D cultures to study the inner workings of the cells during development. Dr. Jasin has discovered two potential drug candidates that are lethal to the breast tumor cultures that carry BRCA2 mutations.
The team will continue investigating whether DNA damage in mammary tissue is caused by DNA replication stress during mammary gland development. In addition, Dr. Jasin plans to examine the effect on breast cancer risk in individuals who carry a BRCA mutation on one chromosome (heterozygous) compared those who have inherited BRCA mutations on both chromosomes (homozygous) versus individuals without BRCA mutations.
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.
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