Joan S. Brugge, PhD

2007-2008 BCRF Project:
The major accomplishment of the Brugge lab during the last grant period was the discovery of a new mechanism of tumor cell death. This mechanism provides novel insights into a phenomenon that has been commonly seen in breast and other types of tumor cells that metastasize to the space surrounding the lung and other fluid-filled cavities. This process of cell death is also observed in approximately 1% -3% of cells within primary human tumors. Dr. Brugge and her team are currently exploring the relevance of this phenomenon on the population dynamics of tumor cells and other aspects of this process in order to understand the role of this process in tumor development.

In addition, last year the Brugge laboratory discovered a new cancer-promoting role for a gene potentially involved in breast, liver, and other kinds of cancers, in collaboration the Haber laboratory at Harvard Medical School. This gene, referred to as YAP, was found to be amplified in a laboratory model of BRCA1 breast cancer, and found by the Brugge laboratory to be a potent oncogene in human breast epithelial cells.

Mid-Year Progress Report:
The major accomplishment of the Brugge lab during the last grant period was the publication of a report describing a process, termed ‘entosis’, that underlies the generation of unusual cell structures that has been described in cancer for decades by pathologists. These structures are composed of cells that contain within their cytoplasm another healthy cell encased in a membrane shell. They are most commonly found in tumor cells that invade into fluid-filled spaces surrounding the lung or in the peritoneum, or even nipple fluid. Interestingly, the researchers find that one cell actually invades into the other cell by an active process involving contraction of structural elements within the invading cell.

The best way to visualize this process is to watch the video on this website: http://www.youtube.com/watch?v=Zp61OzvKRHY. Once inside the other cell, the invading cell can remain as a resident within a protected membrane case for long periods of time. However, eventually the cell is either released or destroyed. These structures are commonly seen in breast and other types of tumor cells that metastasize to the cavity surrounding the lung and other fluid-filled cavities. This process of cell death is also observed in approximately 1-3% of cells within many different primary solid human tumors.

The Brugge team is currently exploring the consequences of this phenomenon on the population dynamics of tumor cells and relevant aspects of tumorigenesis.

Bio:
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.