Joan S. Brugge, PhD
Louise Foote Pfeiffer Professor of Cell Biology
Chair, Department of Cell Biology
Harvard Medical School
2013-2014 BCRF Project:
(The Bloomingdale's Award)
Dr. Brugge’s team completed studies of a complex of proteins that suppress tumor cell invasion and published a report in Cancer Cell describing how this complex functions and how changes in the expression of complex components can provoke more aggressive invasive behavior in human tumors. They also found that this protein is a significant predictor of poor outcome in human breast cancer patients.
In collaboration with fellow BCRF grantee, Dr. Myles Brown (Dana-Farber Cancer Institute), Dr. Brugge identified the functional activities of a protein, PDEF, which is one of the most highly expressed protein in ER-positive breast cancers. These studies show that PDEF can drive differentiation of breast cells and that it is critical for survival of estrogen receptor-positive (ER+) breast tumor cells.
In a separate project, since fall 2012 Dr. Brugge’s team has carried out multiple studies designed to define adaptive responses to targeted treatments for breast cancer. These adaptive responses can significantly decrease the sensitivity of the tumor cells to the targeted therapies and allow maintenance of drug resistant cell populations. Dr. Brugge’s previous studies identified specific niches within the tumor that specifically undergo these responses. Currently, this team has expanded their analysis of the adaptive response to HER2-targeted therapies in vivo. They have also extended their DCIS model to include another HER+ breast tumor cell line, evaluated the response of these two cell lines and others to lapatinib within invasive tumors, and continued to explore conditions to abrogating drug resistance in protective niches by treated with a combination of a HER2-targeted drug and an inhibitor of a critical cell survival protein.
In future studies, Dr. Brugge will further define the nature of the adaptive responses in carcinoma-in-situ and invasive HER1+ tumors and will test combination therapies that abrogate the adaptive response and enhance the efficacy of HER+ therapies.
Joan Brugge joined the faculty of the Department of Cell Biology at Harvard Medical School in July 1997 and became the Chair of this department in 2004. A graduate of Northwestern University, she did her graduate work at the Baylor College of Medicine, completing her PhD in 1975. During her postdoctoral training at the University of Colorado she isolated the protein coded for the viral and cellular forms of the src gene. These proteins were the first viral/cellular oncogene products to be identified, and the study of the normal and oncogenic forms of this gene product has served as a model system to investigate cellular processes that regulate normal growth and the mechanisms involved in tumor formation.
In the 15 years since that discovery, 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 as an investigator at the Howard Hughes Medical Institute. In 1992 Dr. Brugge left academia to help found a new company, ARIAD, to focus on research aimed at developing new drugs for asthma and allergy, cystic fibrosis, cancer, and other diseases that result from cellular regulation gone awry.
Dr. Brugge has received several awards recognizing her scientific accomplishments including an NIH Merit Award, an American Cancer Society Research Professorship and the Senior Career Recognition Award from the American Society of Cell Biology, and she has been elected to the American Academy of Arts and Sciences, the National Academy of Sciences and the Institute of Medicine.