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Maria Jasin, PhD
Professor, Weill Graduate School of Medical Sciences,
Member, Developmental Biology Program
Memorial Sloan Kettering Cancer Center
New York, New York
- Seeking to understand the evolution of BRCA-related breast cancers and identify new therapeutic targets to prevent breast cancer.
- Laboratory studies are conducted to examine the influence of hormone fluctuations and normal mammary gland changes on BRCA-associated breast cancer risk.
- These studies will provide new insight into potential therapeutic targets for prevention of BRCA breast cancers.
Women with inherited mutations in the BRCA genes have a significant risk of developing breast or ovarian cancer. Currently, the only preventive strategy for these women is surgical removal of the breasts and ovaries. Dr. Jasin is conducting studies to understand how changes in the breast during puberty and pregnancy can influence this risk so that better preventive strategies can be developed.
Full Research Summary
Multiple risk factors are linked to breast cancer incidence including reproductive history, exposure to DNA damaging agents and genetic background, such as inherited mutations in BRCA1 and BRCA2 genes.
The goal of Dr. Jasin’s BCRF research is to understand how breast development and hormone exposure during puberty and in pregnancy affect the risk of breast cancer in women with BRCA mutations.
The BRCA1 and BRCA2 genes control key processes in DNA damage repair. When either gene is mutated, cells cannot adequately repair normal DNA damage. This causes damaged DNA to be passed on to daughter cells. Over many cell divisions, DNA damage accumulates and increases the risk of breast and ovarian cancer.
The mammary gland undergoes significant changes during puberty and pregnancy and is highly influenced by fluctuations in its hormonal environment. Little is known, however, about how these changes impact DNA repair and breast cancer susceptibility in women who harbor mutations in the BRCA genes.
These studies may identify potential new targets for breast cancer prevention and treatment strategies.
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.