Titles and Affiliations
Louise Foote Pfeiffer Professor of Cell Biology
Director, Ludwig Center at Harvard
Member, BCRF Scientific Advisory Board
Research area
Using laboratory models to determine the origins of estrogen receptor-positive breast tumors.
Impact
Estrogen receptor (ER)-positive breast cancer and triple-negative breast cancer (TNBC), begin the same way: a normal breast cell acquires the changes that let it grow uncontrollably. In ER-positive breast cancer, estrogen drives tumor growth, yet healthy ER-positive cells do not grow in response to estrogen at all, and the genetic “switch” behind this shift has never been identified. TNBC arises from a distinct, ER-negative cell population governed by a different signaling pathway, and its path to malignancy is similarly unmapped. Dr. Brugge’s research addresses both questions in parallel, using laboratory models to pinpoint the earliest events that transform normal breast cells into the cells that give rise to these two major breast cancer subtypes, work that could point the way toward preventing breast cancer before it starts.
Progress Thus Far
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 for the growth of ER-positive breast cells in the lab and study of their proliferation in response to estrogen. Using these organoids, the team screened for genetic alterations that could drive estrogen-induced proliferation, identifying several promising candidate genes, commonly altered in breast cancer, now being validated and investigated further. They are now applying the same organoid approach to uncover the earliest mutations that initiate TNBC.
What’s next
Dr. Brugge and her team will pursue two parallel goals. For ER-positive breast cancer, the team will identify the most robust candidate genes capable of driving estrogen-induced proliferation and work out the mechanisms underlying this activity. For TNBC, the team will characterize the specific cells of origin within the normal mammary gland, test whether these cells can efficiently give rise to TNBC once relevant cancer-associated genetic alterations are introduced, and evaluate a treatment approach that can suppress tumor development in these cells and prevent TNBC from forming.
Biography
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.
