BBS Faculty Member - Joan Brugge

Joan Brugge

Department of Cell Biology

Harvard Medical School
Building C1, Room 513A
240 Longwood Avenue
Boston, MA 02115

Assistant: Kerry Mojica, 617-432-3973

Tel: 617-432-3974
Fax: 617-432-3969
Lab Members: 11 postdoctoral fellows, 5 graduate students
Visit my lab page here.

We are interested in elucidating the cellular processes and pathways that are involved in the initiation and progression of epithelial tumors. Currently, most of our studies involve investigations relating to breast cancer; however we have recently initiated studies of ovarian tumors as well. One of the major approaches that we use to investigate these processes involves culturing breast epithelial cells basement membrane gels which allows the cells to organize into 3-dimensional structures that resemble the hollow, spherical glandular units of the breast. This culture system allows us to model events that control the proliferation, survival and migration of normal epithelial cells within these structures, to identify cellular genes that allow escape from these controls and induce phenotypic changes resembling those associated with tumor progression, and to elucidate the mechanisms responsible for these events.

One of the major focuses of this project involves studies of cell death processes that are critically involved in the formation of a lumen in the spheroid, gland-like breast epithelial structures and how oncogenes escape these death processes to allow filling of the luminal space. One of the hallmarks of early stage carcinomas filling of the lumen. We have found that multiple processes contribute to the death or clearance of cells from the lumen, including apoptosis, metabolic impairment and autophagy, and intercalation into the outer cell monolayer. Our studies indicate that the induction of apoptosis and autophagy may be a consequence of lack of matrix protein deposition by the inner cells of the acinar structures, so we are investigating how matrix proteins regulate apoptosis and metabolic activity and how oncogenes suppress apoptosis and allow rescue from metabolic impairment. We are also investigating how matrix contributes to drug resistance by regulating the upregulation of survival programs.

Another major focus is on cellular pathways that regulate the aberrant migration and invasion of tumor cells. We have carried out siRNA screens to identify genes that inhibit or enhance cell migration and invasion and are investigating the mechanisms responsible for these events and establishing whether these pathways are involved in invasion in vivo. A major focus is on proteins that regulate cell-cell adhesion and collective migration. We are also investigating pathways that regulate tumor metastasis.

Other studies involve investigations of cellular pathways that control normal differentiation of breast epithelial cells in order to understand the contribution of factors and pathways that regulate these events in tumorigenesis.

Last Update: 12/7/2016


For a complete listing of publications click here.



Overholtzer M, Mailleux AA, Mouneimne G, Normand G, Schnitt SJ, King RW, Cibas ES, Brugge JS. A nonapoptotic cell death process, entosis, that occurs by cell-in-cell invasion. Cell 131 (5): 966-79, 2007.

Simpson KJ, Selfors LM, Bui J, Reynolds A, Leake D, Khvorova A, Brugge JS.
Identification of genes that regulate epithelial cell migration using an siRNA screening approach. Nat Cell Biol, 2008.

Schafer ZT, Grassian AR, Song L, Jiang Z, Gerhart-Hines Z, Irie HY, Gao S, Puigserver P, Brugge JS.
Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment. Nature 2009; 461: 109-113.

Iwanicki MP, Davidowitz RA, Ng MR, Besser A, Muranen T, Merritt M, Danuser G, Ince T, Brugge JS.
Ovarian cancer spheroids use myosin-generated force to clear the mesothelium. Cancer Discovery July 2011 1:144-157

© 2016 President and Fellows
of Harvard College