Harvard Medical School Boston, Massachusetts
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 estrogen signals through the estrogen receptor to drive 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 occurs that makes ER-positive breast cells proliferate in response to estrogen 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 how 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 successfully developed breast ‘mini-organs’, termed organoids, to allow them to study ER-positive breast cells in the lab. Using these organoids, they can investigate the mechanisms associated with ER-positive breast cancer initiation. The team has optimized the organoids and can now grow ER-positive breast cells that behave similarly to breast tissue. In collaboration with BCRF investigator Samuel Aparicio, Dr. Brugge and her team recently identified normal breast cells with genetic changes that display properties suggesting that they are the cells of origin of ER-positive breast cancer.
Dr. Brugge is now poised to begin experiments to identify alterations that initiate the transformation of non-cancerous, ER-positive breast cells into cancerous cells; explore whether rare, proliferative ER-positive cells exist in normal breast tissue; and to determine whether any of the common genetic alterations associated with breast cancer convert ER-positive cells to a proliferative state.
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.
2001
The Play for P.I.N.K. Award
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