Joan S. Brugge, PhD

2009-2010 BCRF Project:
(made possible by generous support from Cartier)

During the last year, the Brugge laboratory has identified a novel mechanism for generation of tumor cells with genomic instability, a hallmark of cancer. This mechanism involves a process that they recently described called entosis, or cell-in-cell formation, in which one cell invades into another. Entosis can lead to genomic stability if the host tumor cell attempts division when another cell is contained within it; the internalized cell prevents the cleavage furrow from successfully separating the two daughter cells, and leads to multinucleation, a process that can promote incorrect segregation of chromosomes.

In addition Dr. Brugge and colleagues have made progress on three other BCRF funded projects involving studies of cancer stem cells and tumor cell invasion. During the coming year, they will continue to pursue ongoing laboratory studies to translate basic findings from their investigations of mammary cell differentiation, cell migration/invasion, and oncogenes to human tumorigenesis and treatment.

Mid-Year Progress Report:
The Brugge laboratory is investigating cellular processes that are involved in cancer progression. In one project, the researchers are studying a recently identified gene,YAP1, that is altered in human cancers. They have discovered a previously unrecognized function for this gene in regulating the final step in cell division, cytokinesis, and have elucidated key steps in this event that are regulated by YAP.

A second project involves studies of a protein, PDEF, which is one of the most commonly upregulated genes in human breast tumors. The researchers have found that this gene can regulate the differentiation of breast cells in culture and are examining if and how this activity regulates normal breast development and how alterations in its expression contribute to breast tumorigenesis.

Lastly, they are studying genes involved in regulating the invasive behavior of tumor cells and recently found that alterations in the mode of actin polymerization through manipulations of key actin assembly factors can trigger invasive behavior in non-invasive tumor cells.

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.