Joan S. Brugge, PhD
Louise Foote Pfeiffer Professor of Cell Biology
Director, Ludwig Center at Harvard
Member, BCRF Scientific Advisory Board
Using laboratory models to determine the origins of estrogen receptor-positive breast tumors.
In estrogen receptor (ER)-positive breast cancer, the most common form of breast cancer, tumor cells make ER and estrogen signals through this receptor to promote tumor growth. In contrast, in non-cancerous breast tissue, breast cells can be ER-positive, but they do not grow in response to estrogen. The ‘switch’ that converts estrogen into a growth-promoting factor in ER-positive cells has not been identified. Understanding how this switch happens could shed light on how ER-positive breast cancer is initiated and, ultimately, how to prevent it.
Until recently, studying the evolution of ER-positive breast cells and the mechanisms by which they become malignant cancer cells has been limited because ER-positive breast cells are difficult to grow in laboratory cell cultures. Dr. Brugge and her team are developing breast ‘mini-organs’, termed organoids, to allow for the study of ER-positive breast cells in the lab. Using these organoids, they will investigate the mechanisms associated with ER-positive breast cancer initiation. During the last year, the team overcame important barriers to progress including: 1) identifying how to maintain ER-positive cells in organoid culture; and 2) determining what conditions allow the cells to respond to estradiol. In addition to their laboratory model, they also use human breast tumors to conduct genomic profiling. The genes they identified in this analysis will inform which genetic alterations could promote survival or tumor progression in the organoid systems.
Dr. Brugge and her team will continue to optimize their methods for organoid culture, a technically challenging process. They will then perform studies to determine the evolution of ER-positive breast cancer. These experiments will identify genes and pathways that play a role in this process.
Dr. Brugge is Co-Director of the Ludwig Center at Harvard Medical School. A graduate of Northwestern University, she did graduate work at the Baylor College of Medicine, completing her PhD in 1975, followed by postdoctoral training at the University of Colorado with Dr. Raymond Erikson. Dr. Brugge has held full professorships at the State University of New York, Stony Brook, and the University of Pennsylvania, where she was also named an investigator at the Howard Hughes Medical Institute. From 1992-1997 Dr. Brugge was Scientific Director of the biotechnology company ARIAD. She joined Harvard in 1997 as Professor of Cell Biology, was Chair of Cell Biology from 2004 - 2014, and became Co-Director of the Ludwig Center at Harvard in 2014.
Dr. Brugge’s awards include an NIH Merit Award, an American Cancer Society Research Professorship and the Senior Career Recognition Award from the American Society of Cell Biology. She is the recipient of BCRF's 2015 Jill Rose Award for research excellence. She has been elected to the American Academy of Arts and Sciences, the National Academy of Sciences and the Institute of Medicine.
Dr. Brugge is investigating the mechanisms involved in breast cancer initiation and progression. Her laboratory has utilized three dimensional cultures of normal breast cells and breast tumor cells to recapitulate the organization of cells in their natural context and provide important insights relating to the mechanisms whereby genes that are altered in breast cancer contribute to tumor formation and progression as well as those that mediate resistance to cancer therapies.
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